Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

New insights into the persistent effect of transient cinnamaldehyde vapor treatment on the growth and aflatoxin synthesis of Aspergillus flavus.

The antimicrobial effects of continuous treatment with essential oils (EOs) in both liquid and gaseous phases have been intensively studied. Due to their rapid volatility, the effects of EOs on microorganisms after transient treatment are also worth exploring. In this work, the persistent effects of cinnamaldehyde (CA) vapor on Aspergillus flavus were detected by a series of biochemical analyses. Transcriptome analysis was also conducted to study the gene expression changes between recovered and normal A. flavus. When CA vapor was removed, biochemical analyses showed that the oxidative stress induced by the antimicrobial atmosphere was alleviated, and almost all the damaged functions were restored apart from mitochondrial function. Remarkably, the suppressed aflatoxin production intensified, which was confirmed by the up-regulation of most genes in the aflatoxin synthetic gene cluster, the velvet-related gene FluG and the aflatoxin precursor acetyl-CoA. Transcriptomic analysis also demonstrated significant changes in secondary metabolism, energy metabolism, oxidative stress, and amino acid metabolism in the recovery group. Taken together, these findings provide new insights into the mechanisms underlying the response of A. flavus to CA vapor treatment and will guide the rational application of EOs.

Sodium Butyrate Attenuated Diabetes-Induced Intestinal Inflammation by Modulating Gut Microbiota.

Background: Diabetes mellitus (DM) continues to be one of the world's most costly and complex metabolic disorders. Accumulating evidence has shown that intestinal dysbiosis and associated inflammation can facilitate the onset and progression of DM. In this work, our goal was to investigate how sodium butyrate (SB) controls the gut microbiota to reduce the intestinal inflammation brought on by diabetes. Methods: Male KK-Ay mice were randomized into two groups: the DM model group (intragastric administration of 0.9% normal saline) and the SB treatment group (intragastric administration of 1,000 mg/kg/d SB). The C57BL/6J mice were used as the control group (intragastric administration of 0.9% normal saline). These mice were administered via gavage for 8 weeks. Results: The results revealed that SB-treated mice significantly reduced fasting blood glucose (FBG), body weight, 24 h food and water intake, and improved islet histopathology in DM model mice. SB reduced TNF-α, IL-1ß, and iNOS, whereas it enhanced the expression of the anti-inflammatory Arg-1 marker on intestinal macrophages and the secretion of anti-inflammatory IL-10. Specifically, SB was linked to a marked drop in the expression of the Th17 marker RORγt and a substantial increase in the expression of the Treg marker Foxp3. SB treatment was associated with significant reductions in the levels of Th17-derived cytokines such as IL-17 and IL-6, whereas anti-inflammatory Treg-derived cytokines such as TGF-ß were increased. Additionally, the analysis results from 16S rDNA sequencing suggested that SB significantly reversed the variations in intestinal flora distribution and decreased the relative abundance of Weissella confusa and Anaerotruncus colihominis DSM 17241 at the species level as well as Leuconostocaceae, Streptococcaceae, and Christensenellaceae at the family, genus, and species levels. These distinct florae may serve as a diagnostic biomarker for DM-induced intestinal inflammation. In addition, the heat map of phylum and OTU level revealed a close relationship between DM-induced intestinal inflammation and intestinal microbiota. Conclusions: The present study suggested that SB may reduce DM-induced intestinal inflammation by regulating the gut microbiota.

Updated Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of Natural Product Geniposide.

At present, the potential of natural products in new drug development has attracted more and more scientists' attention, and natural products have become an important source for the treatment of various diseases or important lead compounds. Geniposide, as a novel iridoid glycoside compound, is an active natural product isolated from the herb Gardenia jasminoides Ellis (GJ) for the first time; it is also the main active component of GJ. Recent studies have found that geniposide has multiple pharmacological effects and biological activities, including hepatoprotective activity, an anti-osteoporosis effect, an antitumor effect, an anti-diabetic effect, ananti-myocardial dysfunction effect, a neuroprotective effect, and other protective effects. In this study, the latest research progress of the natural product geniposide is systematically described, and the pharmacological effects, pharmacokinetics, and toxicity of geniposide are also summarized and discussed comprehensively. We also emphasize the major pathways modulated by geniposide, offering new insights into the pharmacological effects of geniposide as a promising drug candidate for multiple disorders.

The Herb Pair Radix Rehmanniae and Cornus Officinalis Attenuated Testicular Damage in Mice With Diabetes Mellitus Through Butyric Acid/Glucagon-Like Peptide-1/Glucagon-Like Peptide-1 Receptor Pathway Mediated by Gut Microbiota.

Growing body of research indicates that Traditional Chinese Medicine (TCM) interact with gut microbiota (GM) after oral administration. Radix Rehmanniae and Cornus Officinalis (RR-CO), a well-known TCM pair, is often used to treat diabetes mellitus (DM) and its complications. The current study aimed to explore the protective effects of RR-CO on DM induced testicular damage by modulating GM. The RR-CO treatments significantly reduced hyperglycemia, ameliorated testicular ultrastructural damage and inflammation in DM model to varying degrees. Additionally, 16S-ribosomal DNA (rDNA) sequencing results showed that RR-CO treatment increased the amount of butyric acid-producing GM, such as Clostridiaceae_1 family, and decreased the abundance of Catabacter, Marvinbryantia, and Helicobacter genera. RR-CO fecal bacteria transplantation (RC-FMT) increased the abundance of Clostridiaceae_1 in the Model FMT (M-FMT) group and ameliorated testicular damage. Furthermore, treatment with RR-CO increased the fecal butyric acid level, serum Glucagon-like peptide-1 (GLP-1) level, and testicular GLP-1 receptor (GLP-1R) expression compared to those in DM mice. Finally, intraperitoneal administration of sodium butyrate (SB) significantly improved the pathological damage to the testis and reduced inflammation in the DM group. These data demonstrated a protective effect of RR-CO on DM-induced testicular damage by modulation of GM, which may be mediated by the butyric acid/GLP/GLP-1R pathway.

Cornuside Alleviates Diabetes Mellitus-Induced Testicular Damage by Modulating the Gut Microbiota.

BACKGROUND: Male reproductive damage, as a common complication of diabetes mellitus (DM), is getting more attention lately. We aimed to explore the protective effects and mechanism of cornuside (Cor) modulating gut microbiota to alleviate diabetes mellitus- (DM-) induced testicular damage. METHODS: KK-Ay mice with reproductive damage were randomly divided into the model and Cor treatment groups, and the C57BL/6J mice were used as the normal group. These mice were orally administered Cor for 8 weeks. RESULTS: Cor administration ameliorated the diabetes-related symptoms of polydipsia and polyphagia and lowered the fasting blood glucose (FBG) level. The results of pathological injury showed that Cor improved testicular lesions (the rupture of seminiferous tubules, degeneration of germ cells, and structural shrinkage and separation from each other) in DM model mice. Cor significantly increased the testis/body weight ratio, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in KK-Ay mice. Cor also protected from reproductive damage by inhibiting apoptosis in the testes of KK-Ay mice. Moreover, Cor significantly increased the sperm count and sperm motility. Additionally, 16S rDNA sequencing analysis showed that Cor could notably reverse the changes in the distribution of gut microbiota and decrease the abundance of Weissella confusa (Weissella), Clostridium sp. ND2 (Clostridium sensu stricto 1), uncultured bacterium (Roseburia), Anaerotruncus colihominis DSM 17241 (Anaerotruncus), [Clostridium] leptum (Anaerotruncus), unidentified (Ruminococcus 1), and uncultured bacterium (Bilophila), which may be a potential biomarker for diagnosing the testicular injury caused by DM. Meanwhile, the heat map of phylum level suggested that the testicular injury caused by DM is closely related to gut microbiota. CONCLUSIONS: Cor could alleviate DM-induced testicular damage, probably by modulating the gut microbiota.

Combination of the Herbs Radix Rehmanniae and Cornus Officinalis Mitigated Testicular Damage From Diabetes Mellitus by Enhancing Glycolysis via the AGEs/RAGE/HIF-1α Axis.

Radix Rehmanniae and Cornus Officinalis (RR-CO) have been widely used as "nourishing Yin and tonifying kidney" herb pairs for the treatment of diabetes mellitus (DM) and its complications in traditional Chinese medicine (TCM). Based on the theory of "kidney governing reproduction" in TCM, the aim of this study was to investigate the therapeutic effects of RR-CO on DM-induced reproduction damage through regulating testicular glycolysis. Moreover, the regulation of AGEs/RAGE/HIF-1α axis on the testicular glycolysis process has also been studied. Spontaneous DM model KK-Ay mice were used to investigate the protective effect of RR, CO, RR-CO on DM-induced reproductive disturbances. RR, CO, RR-CO improved DM-induced renal and testicular morphology damages. Moreover, the impaired spermatogenesis, germ cell apoptosis and motility in testis induced upon DM were also attenuated by RR, CO or RR-CO, accompanied by an increased level of glycolysis metabolomics such as l-lactate, d-Fructose 1,6-bisphosphate, etc. Meanwhile, glucose membrane transporters (GLUT1, GLUT3), monocarboxylate transporter 4 (MCT4) expression, lactate dehydrogenase (LDH) activity, HIF-1α were upregulated by RR, CO and RR-CO treatment compared with the model group, whereas AGE level and RAGE expression were decreased with the drug administration. The RR-CO group was associated with superior protective effects in comparison to RR, CO use only. Aminoguanidine (Ami) and FPS-ZM1, the AGEs and RAGE inhibitors, were used as a tool drug to study the mechanism, showing different degrees of protection against DM-induced reproductive damage. This work preliminarily sheds light on the herb pair RR-CO exhibited favorable effects against DM-induced reproductive disturbances through enhancing testicular glycolysis, which might be mediated by AGEs/RAGE/HIF-1α axis.

Radix Rehmanniae and Corni Fructus against Diabetic Nephropathy via AGE-RAGE Signaling Pathway.

BACKGROUND AND AIMS: Radix Rehmanniae and Corni Fructus (RC) have been widely applied to treat diabetic nephropathy (DN) for centuries. But the mechanism of how RC plays the therapeutic role against DN is unclear as yet. METHODS: The information about RC was obtained from a public database. The active compounds of RC were screened by oral bioavailability (OB) and drug-likeness (DL). Gene ontology (GO) analysis was performed to realize the key targets of RC, and an active compound-potential target network was created. The therapeutic effects of RC active compounds and their key signal pathways were preliminarily probed via network pharmacology analysis and animal experiments. RESULTS: In this study, 29 active compounds from RC and 64 key targets related to DN were collected using the network pharmacology method. The pathway enrichment analysis showed that RC regulated advanced glycosylation end product (AGE-) RAGE and IL-17 signaling pathways to treat DN. The animal experiments revealed that RC significantly improved metabolic parameters, inflammation renal structure, and function to protect the kidney against DN. CONCLUSIONS: The results revealed the relationship between multicomponents and multitargets of RC. The administratiom of RC might remit the DM-induced renal damage through the AGE-RAGE signaling pathway to improve metabolic parameters and protect renal structure and function.

Surface modification of black phosphorus-based nanomaterials in biomedical applications: Strategies and recent advances.

Black phosphorus-based nanomaterials (BPNMs), an emerging member of two-dimensional (2D) nanomaterials, possess excellent physicochemical properties and hold great potential for application in advanced nanomedicines. However, the bare BPNMs easily decrease their biomedical activities due to their degradability and in vivo interactions with biological macromolecules such as plasma proteins, largely restricting their biomedical application. A variety of surface modifications, via chemical, physical or biological approaches, have been developed for BPNMs to avoid these limitations and achieve stable, long-lasting and safe therapeutic effects, thus enlighten the development of the multifunctional BPNMs for more practical application in the field of biomedicine. The present review summarizes the recent advances in the surface modification of BPNMs and the resultant expansion of their biomedical applications. Focus is put on the strategy and method of modification while the effects incurred on the behavior and potential toxicity of BPNMs are also included. The future and challenge of the surface modification of the therapeutic BPNMs are finally discussed.

Deoxyelephantopin decreases the release of inflammatory cytokines in macrophage associated with attenuation of aerobic glycolysis via modulation of PKM2.

Growing evidence suggests that activated immune cells undergo metabolic reprogramming in the regulation of the innate inflammatory response. Remarkably, macrophages activated by lipopolysaccharide (LPS) induce a switch from oxidative phosphorylation to aerobic glycolysis, and consequently results in release of proinflammatory cytokines. Pyruvate Kinase M2 (PKM2) plays a vital role in the process of macrophage activation, promoting the inflammatory response in sepsis and septic shock. Deoxyelephantopin (DET), a naturally occurring sesquiterpene lactone from Elephantopus scaber, has been shown to counteracts inflammation during fulminant hepatitis progression, but the underlying mechanism remains unclear. Here, we studied the function of the DET on macrophage activation and investigated the anti-inflammatory effects of DET associated with interfering with glycolysis in macrophage. Our results first demonstrated that DET attenuates LPS-induced interleukin-1ß (IL-1ß) and high-mobility group box 1 (HMGB1) release in vitro and in vivo and protected mice against lethal endotoxemia. Furthermore, DET decreased the expression of pyruvate dehydrogenase kinase 1 (PDK1), glucose transporter 1(GLUT1), lactate dehydrogenase A (LDHA), and reduced lactate production dose-dependently in macrophages. Moreover, we further revealed that DET attenuates aerobic glycolysis in macrophages associated with regulating the nuclear localization of PKM2. Our results provided a novel mechanism for DET suppression of macrophages activation implicated in anti-inflammatory therapy.

Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype.

Phenotype switching is a characteristic response of vascular smooth muscle cells (vSMCs) to the dynamic microenvironment and contributes to all stages of atherosclerotic plaque. Here, we immersed pure magnesium and AZ31 alloy in the completed medium under cell culture condition, applied the resultant leaching extracts to the isolated contractile rat aortic vSMCs and investigated how vSMCs phenotypically responded to the degradation of the magnesium-based stent materials. vSMCs became more proliferative and migratory but underwent more apoptosis when exposed to the degradation products of pure magnesium; while the AZ31 extracts caused less cell division but more apoptosis, thus slowing cell moving and growing. Noticeably, both leaching extracts dramatically downregulated the contractile phenotypic genes at mRNA and protein levels while significantly induced the inflammatory adhesive molecules and cytokines. Exogenously added Mg ions excited similar transformations of vSMCs. With the liberation or supplementation of Mg2+ , the expression patterns of the pro-contractile transactivator myocardin and the pro-inflammatory transcriptional factor kruppel-like factor 4 (KLF4) were reversed. Overall, the degradation of the Mg-based materials would evoke a shift of the contractile vSMCs to an inflammatory phenotype via releasing Mg ions to induce a transition from the phenotypic control of vSMCs by the myocardin to that by the KLF4. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 988-1001, 2019.

Facile fabrication of a novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is one of the greatest public health problems worldwide, and chemotherapy remains the major approach for the HCC treatment. Doxorubicin (DOX) is one of the anthracycline antibiotics but its clinical use is limited due to its severe cardiotoxicity. In this study, novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates (PDC-NPs) were fabricated for HCC treatment. The stabilized structure of the PDC-NPs was characterized by methylene blue absorption, the size, zeta potential and the morphology, which was investigated by Zetasizer nanoparticle analyzer and transmission electron microscope (TEM), of nanoparticles. The PDC-NPs achieved a sustained and prolonged release ability, which was illustrated with in vitro drug release profiles, anti-cell proliferation study, cellular uptake assay and in vivo pharmacokinetics analysis. Biocompatibility of the PDC-NPs was assessed with bovine serum albumin (BSA) adsorption test, hemolysis activity examination and viability evaluation of human umbilical vein endothelial cells. Importantly, in vivo studies of the PDC-NPs, which were performed in the athymic BALB/c nude mice, demonstrated that the PDC-NPs significantly reduced the lethal side effect of DOX. Additionally, the H&E staining and serum biochemistry study further confirmed the excellent biological security of the PDC-NPs.

Iridoid glycoside from Cornus officinalis ameliorated diabetes mellitus-induced testicular damage in male rats: Involvement of suppression of the AGEs/RAGE/p38 MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis (CO) has been widely used as a traditional Chinese medicine for treating diabetes mellitus (DM) and its complications. Iridoid glycoside from C. officinalis (IGCO) can resist apoptosis, hyperglycemia, oxidation and so on. The aim of this study was to investigate the therapeutic effects of IGCO on DM-induced testicular damage through inhibition of the AGEs/RAGE/p38 MAPK signaling pathway. MATERIALS AND METHODS: A DM model of male Wistar rats was induced with streptozotocin injection (30mg/kg, i.p.) and high-fat diet. The DM rats were administrated with IGCO at low and high doses (15 and 30mg/kg, p.o.) for 12 weeks. Testicular damage was evaluated by estimating relative testicular weights, testicular pathohistology, sperm count, live sperm rate, endogenous sex hormone level and activity of testicular marker enzymes. Besides, general diabetic symptoms, renal function, oxidative stress parameters and testicular apoptosis marker were also determined. Finally, the mechanism was explored based on the AGEs/RAGE/p38 MAPK pathway. RESULTS: IGCO effectively mitigated the general symptoms of DM rats including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose level and low serum insulin level. Nourishing the kidney evidently, IGCO reduced serum creatinine, urea nitrogen and urine protein excretion, and also markedly protected against DM-induced testicular damage by increasing testis/body weight ratio and live sperm rate, improving the histomorphology of testes, upregulating testosterone, LH, FSH and GnRH levels and preventing the decrease of testicular marker enzymes LDH, ACP and γ-GT. Moreover, IGCO showed considerable anti-oxidative and anti-apoptotic effects, which downregulated the increase of ROS and MDA levels, restored SOD and CAT activities, and decreased spermatogenic cell apoptosis and Bax/Bcl-2 ratio. In the end, the increased AGEs, RAGE and p-p38 MAPK protein levels in DM rats were also reversed by IGCO significantly. CONCLUSIONS: The kidney tonic IGCO well protected DM rats from testicular damage, which may be related to suppression of the AGEs-RAGE-p38 MAPK pathway.

Effects of wheelchair Tai Chi on physical and mental health among elderly with disability.

A 12-week Wheelchair Tai Chi 10 Form (WTC10) intervention was conducted among elderly with disability to examine the effect of this WTC10 intervention on selected physical and mental health variables. Thirteen (age 87.23 ± 6.71) in the WTC10 intervention group and 15 (age 89.73 ± 6.31) in the control group completed the study. Independent t-tests and paired t-tests were employed to examine the differences between groups and within groups, respectively, at pretest and post-test. The WTC10 intervention group showed significant improvements in systolic and diastolic blood pressure, shoulder external rotation, left trunk rotation and total trunk rotation after the intervention. A 12-week WTC10 intervention had positive effects on blood pressure, range of motion at the shoulder and trunk, physical activity, and mental health among the elderly with disability. WTC10 is a feasible and safe exercise for the elderly with disability.

Synergistic interaction of effective parts in Rehmanniae Radix and Cornus officinalis ameliorates renal injury in C57BL/KsJ-db/db diabetic mice: Involvement of suppression of AGEs/RAGE/SphK1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmanniae Radix (RR) and Cornus officinalis (CO) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic nephropathy. Iridoid glycoside of Cornus officinalis (IGCO), triterpenoid acid of Cornus officinalis (TACO) and iridoid glycoside of Rehmanniae Radix (IGRR) formed an innovative formula named combinatorial bioactive parts (CBP). The aims of the present study were to investigate the renoprotective effects of CBP on DN through the inhibition of AGEs/RAGE/SphK1 signaling pathway activation, and identify the advantage of CBP compared with IGCO, TACO, IGRR. MATERIALS AND METHODS: The db/db diabetic renal injury model was used to examine the renoprotective effects of CBP, IGCO, TACO and IGRR. For mechanistic studies, diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGEs/RAGE/SphK1 pathway were determined. RESULTS: CBP, IGCO, TACO and IGRR inhibited the decrease in serum insulin levels and the increases in urine volume, food consumption, water intake, TC, TG, glycated serum protein, fasting blood glucose levels, 24h urine protein levels, and serum levels of urea nitrogen and creatinine. It also prevented ECM accumulation and improved the histology of pancreas and kidney, and alleviated the structural alterations in mesangial cells and podocytes in renal cortex. Moreover, CBP, IGCO, TACO and IGRR down-regulated the elevated staining, protein levels of RAGE, SphK1, TGF-ß and NF-κB. Among the treatment groups, CBP produced the strongest effects. CONCLUSIONS: These findings suggest that the inhibitory effect of CBP, IGCO, TACO and IGRR on the activation of AGEs/RAGE/SphK1 signaling pathway in db/db diabetic mice kidney is a novel mechanism by which CBP, IGCO, TACO and IGRR exerts renoprotective effects on DN. Among all the groups, CBP produced the strongest effect while IGCO, TACO and IGRR produced weaker effects.

From "Where" to "What": Distributed Representations of Brand Associations in the Human Brain.

Considerable attention has been given to the notion that there exists a set of human-like characteristics associated with brands, referred to as brand personality. Here we combine newly available machine learning techniques with functional neuroimaging data to characterize the set of processes that give rise to these associations. We show that brand personality traits can be captured by the weighted activity across a widely distributed set of brain regions previously implicated in reasoning, imagery, and affective processing. That is, as opposed to being constructed via reflective processes, brand personality traits appear to exist a priori inside the minds of consumers, such that we were able to predict what brand a person is thinking about based solely on the relationship between brand personality associations and brain activity. These findings represent an important advance in the application of neuroscientific methods to consumer research, moving from work focused on cataloguing brain regions associated with marketing stimuli to testing and refining mental constructs central to theories of consumer behavior.

A cohort study on myasthenia gravis patients in China.

Clinical classification and age distribution in myasthenia gravis (MG) cases seem different between Oriental and Caucasian populations, but there have rarely been any clinical studies on MG patients from mainland China. The goal of the current study was to perform a comprehensive survey of myasthenia gravis in a hospital in China, establishing contemporary cohort data and clinical features. 1,108 unselected patients with MG attending the 309th Hospital of PLA, Beijing, China were studied during a 36-month period from July 2008 to June 2011. The sex ratio was 1:1 (F:M). 62.5 % of patients presented as adolescents and adults. Ocular MG cases accounted for 65.6 % childhood MG patients. A positive response was observed in 96.8 % of the patients for neostigmine tests, whereas a positive decremental response to low frequency repetitive nerve stimulation (RNS) was observed in 77.4 % of the patients. The highest stimulating positive rate was 65.3 % in stimulated facial nerve. Thymoma was significantly increased in those patients with severe MG, especially in the cohort involving the respiratory muscles (p < 0.001). The study revealed higher frequency of ocular and childhood MG compared to other studies in USA and European countries, which can be a result of optimum case ascertainment, increased disease duration, or application of complex diagnostic tests. The relative increase in the prevalence of ocular myasthenia can be attributed to the impact of an aging population.

[Quality standard of Sappan Lignum].

To establish the quality standard of Sappan Lignum, TLC and HPLC method were employed. The components of Sappan Lignum could be separated well on GF254 thin layer plate using a mixture of chloroform-acetone-formic acid (8:4:1) as the mobile phase, and the 18 samples collected basically showed the same spots. The ethanol-soluble extractives of 18 samples varied in the range of 6.4% to 11.3%. The methodological investigation of assay showed, the peak areas and the injection amount of Brazilin and (+/-) protosappanin B were in good linear correlation when their amounts were in the ranges of 0.362-5.425 microg and 0.313-4.695 microg, with the regression equations of Y = 798,999.57X - 219,666.54 (r = 0.9997) and Y = 930,296.63X - 123,330.67 (r = 0.9995) and the average recoveries were 98.6% and 100.5%, respectively. The contents differed significantly among the samples. The TLC identification method established was suitable to identify Sappan Lignum due to its strong specificity. The HPLC assay method established could be applied to the quality control of Sappan Lignum due to its convenience, good reproducibility and high accuracy.

[Determination of vaccarin in Vaccariae Semen by HPLC].

To establish a HPLC method for the determination of vaccarin in Vaccariae Semen. Analysis was carried out on an Alltima-C18 column (4.6 mm x 250 mm, 5 microm) eluted with methanol -0.3% phosphoric acid as mobile phase in gradient elution. The flow rate was 1.0 mL x min(-1) and detected wavelength was set at 280 nm. The peak areas and injection ammounts of vaccarin showed a good linear relationship in the range of 0.102-1.539 microg, R2 = 0.9997. The average recovery was 100.4%, RSD was 0.81%. The results of the assay of 10 samples showed that the contents of vaccarin varied in the range of 0.46%-0.57%. The method is simple, accurate, reproducible and specific. It can be used for the quality control of Vaccariae Semen.

[Flavonoids from Artemisia anomala].

OBJECTIVE: To study the constituents of Artemisia anomala. METHOD: The constituents were isolated by chromatographic methods, their structures were elucidated by spectroscopic evidences. RESULT: Eleven flavonoids and two flavanolignans were purified and their structures were identified. CONCLUSION: Compound 12 and 13 were isolated from the Compositae family for the first time. Compound 5 and 9 were firstly isolated from the genus Artemisia. Compounds 4, 7, 11 were isolated from A. anomala for the first time.