The Analysis of Serum Klotho Protein Level and Related Gene Polymorphism in Osteoporotic Fracture of Elderly Patients with Osteoporosis.

Objective: Klotho protein level are reported to play important roles in the osteoporosis. To investigate the correlation between serum Klotho protein level and related gene (Klotho G395-A gene) polymorphism and osteoporotic fracture in elderly patients with osteoporosis. Methods: A total of 62 elderly patients with osteoporosis admitted to the Department of Orthopedics of our hospital from January 2021 to June 2022 were included in the study group. Another 62 elderly patients without osteoporosis who underwent a physical examination at the same time were selected as the control group. Patients in the study group were divided into group A (n = 23, osteoporotic fracture) and group B (n = 39, osteoporotic fracture) according to the occurrence of osteoporotic fracture. Serum Klotho protein level was detected in all patients, and its related gene (Klotho G395-A gene) polymorphism was analyzed. After fasting in the morning (fasting for more than 8 hours), 3-5 ml venous blood was collected and immediately placed in a centrifuge tube. Serum was separated and serum Klotho protein level was measured by enzyme-linked immunosorbent assay kit. Polymorphism typing was performed by Taqman allele-specific hybridization analysis. At the same time, general information (gender, age, body mass index, systolic blood pressure, diastolic blood pressure, glycated glucose protein, low-density lipoprotein cholesterol, bone mineral density) was collected. The differences in general data, serum Klotho protein level and Klotho G395-A gene polymorphism between the study group and the control group were analyzed. Spearman analysis was used to analyze the correlation between general data, serum Klotho protein level and Klotho G395-A gene and osteoporotic fracture. Logistic analysis was used to analyze the independent risk factors of osteoporotic fracture. Results: There was no significant difference of the sex, systolic blood pressure (SBP), diastolic blood pressure (DBP), Klotho G395-A genotype GG and alleles A and G between the study group and the control group. There was significant difference of body mass index (BMI), glycated glucose protein, low-density lipoprotein cholesterol (LDL-C), bone mineral density, serum Klotho protein level and Klotho G395-A genotype AA and AG were between the study group and the control group. Gender, age, glycated glucose protein and Klotho G395-A genotype AA were positively correlated with osteoporotic fracture (P < .05), while bone mineral density was negatively correlated with osteoporotic fracture (P < .05). There was no correlationship between the serum Klotho protein level and the incidence of osteoporotic fracture (P > .05). Logistic analysis showed that age, bone mineral density and Klotho G395-A genotype AA were independent risk factors for osteoporotic fracture. Conclusion: The level of serum Klotho protein and related gene polymorphisms are both related to osteoporotic fracture in elderly patients with osteoporosis. It is significant to reduce the incidence of osteoporotic fractures. In future, more experiments are needed to explore the underlying mechanism.

Effectiveness of Scutellaria baicalensis Georgi root in pregnancy-related diseases: A review / 中西医结合学报

The root of Scutellaria baicalensis Georgi, also called Huangqin, is frequently used in traditional Chinese medicine. In ancient China, S. baicalensis root was used to clear heat, protect the fetus, and avoid a miscarriage for thousands of years. In modern times, pregnancy-related diseases can seriously affect maternal and fetal health, but few systematic studies have explored the mechanisms and potential targets of S. baicalensis root in the treatment of pregnancy-related diseases. Flavonoids (baicalein, wogonin and oroxylin A) and flavonoid glycosides (baicalin and wogonoside) are the main chemical components in the root of S. baicalensis. This study presents the current understanding of the major chemical components in the root of S. baicalensis, focusing on their traditional uses, potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders. The mechanisms, potential targets and experimental models of S. baicalensis root for ameliorating pregnancy-related diseases, such as recurrent spontaneous abortion, preeclampsia, preterm birth, fetal growth restriction and gestational diabetes mellitus, are highlighted.

Profile and activity of phenolic antioxidants in chrysanthemum (Huangshan Gongju) as affected by simulated digestions.

The phenolics are the main bioactive substances of Huangshan Gongju, a famous chrysanthemum of China, but their digestive characteristics are still unknown. To explore the digestive properties of Huangshan Gongju phenolics, the flower was extracted and subjected to simulated digestions, and their phenolic profile and activity were analyzed. The results indicated that the total phenolics content and antioxidant activity of the extract varied with the simulated digestion steps, and they generally decreased in the oral and small intestine digestions but increased in the gastric digestion, and high correlations were detected between the total phenolics content and antioxidant activity (0.873 < r < 0.979, p < .01). The change of phenolic profile during the simulated digestions was similar to that of total phenolics content, and six individual phenolics were identified and quantified, and three of them, including chlorogenic acid, apigenin-7-O-rutinoside, and apigenin-7-O-6″-acetylglucoside showed higher recovery (>64.29%), implying they may be the main functional phenolics of Huangshan Gongju. PRACTICAL APPLICATIONS: This study proved that most phenolics in Huangshan Gongju were relatively stable during digestion. The finding may guarantee the application of Huangshan Gongju in the field of functional foods.

The efficacy of Yiqi Huoxue therapy for chronic heart failure: A meta-analysis in accordance with PRISMA guideline.

BACKGROUND: Chronic heart failure (CHF) is the final destination of most cardiovascular diseases and the most important cause of death. The main clinical manifestations were pulmonary congestion and decreased cardiac output. The purpose of this systematic review is to evaluate the effectiveness of Yiqi Huoxue therapy on CHF. METHODS: Seven electronic databases were searched to identify randomized controlled trials of Yiqi Huoxue (YQHX) method for CHF until April 30, 2020. The quality assessment of the included trials was performed by employing the Cochrane Risk of Bias tool and Jadad scale. RESULTS: Nineteen randomized controlled trials were included in our review. Most of the included trials were considered as low quality. The aggregated results suggested that experimental group with YQHX therapy got better effect in increasing overall response rate (risk ratio, RR = 1.21, 95% confidence interval, CI 1.15-1.27), traditional Chinese medicine (TCM) syndrome response rate (RR = 1.26, 95% CI 1.17-1.36), 6-minute walk test (RR = 2.14, 95% CI 1.05-3.22), left ventricular ejection fraction (RR = 0.97, 95% CI 0.60-1.34), and stroke volume (standardized mean difference, SMD = 0.94, 95% CI 0.23-1.56), and in lowering down the TCM syndrome scores (SMD = -0.78, 95% CI -0.91 to -0.64), Minnesota Living with Heart Failure questionnaire (SMD = -1.01, 95% CI -1.56 to -0.45), 6-month readmission rate (RR = 0.50, 95% CI 0.28-0.89), B-type natriuretic peptide (SMD = -0.89, 95% CI -1.52 to -0.25), NT-proBNP (SMD = -2.07, 95% CI -3.34 to -0.08), and C-reactive protein (SMD = -2.04, 95% CI -4.12 to -0.67) as compared to using conventional Western medicine alone. There were no significant differences found in left ventricular end diastolic diameter and E/E' between experimental groups and control groups. Moreover, the included sample capacity is small and the trails are all in Chinese. Quality of the evidence for outcomes were "low" and "very low" according to the GRADE assessment. CONCLUSION: YQHX is a valid complementary and alternative therapy in the management of CHF, especially in improving overall response rate, TCM syndrome response rate, 6-minute walk test, left ventricular ejection fraction, and stroke volume and in decreasing TCM syndrome scores, Minnesota Living with Heart Failure questionnaire, 6-month readmission rate, B-type natriuretic peptide, NT-proBNP, and C-reactive protein levels. Hence, YQHX is a relatively effective and safe therapy for CHF patients, which can be popularized and applied in the clinic. More long-term follow-up studies are still needed to substantiate and confirm the current findings.

[Effect of Shanhaidan Granules combined with tadalafil on erectile dysfunction: A multi-center clinical trial].

OBJECTIVE: To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED. METHODS: In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients. RESULTS: After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators. CONCLUSIONS: Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.

Spacetime in the brain: rapid brain network reorganization in visual processing and recovery.

Functional connectivity networks (FCN) are the physiological basis of brain synchronization to integrating neural activity. They are not rigid but can reorganize under pathological conditions or during mental or behavioral states. However, because mental acts can be very fast, like the blink of an eye, we now used the visual system as a model to explore rapid FCN reorganization and its functional impact in normal, abnormal and post treatment vision. EEG-recordings were time-locked to visual stimulus presentation; graph analysis of neurophysiological oscillations were used to characterize millisecond FCN dynamics in healthy subjects and in patients with optic nerve damage before and after neuromodulation with alternating currents stimulation and were correlated with visual performance. We showed that rapid and transient FCN synchronization patterns in humans can evolve and dissolve in millisecond speed during visual processing. This rapid FCN reorganization is functionally relevant because disruption and recovery after treatment in optic nerve patients correlated with impaired and recovered visual performance, respectively. Because FCN hub and node interactions can evolve and dissolve in millisecond speed to manage spatial and temporal neural synchronization during visual processing and recovery, we propose "Brain Spacetime" as a fundamental principle of the human mind not only in visual cognition but also in vision restoration.

Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression.

While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the hypothalamic perifornical area (PeFAUcn3) are activated during infant-directed attacks in males and females, but not other behaviors. Functional manipulations of PeFAUcn3 neurons demonstrate the role of this population in the negative control of parenting in both sexes. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send projections to hypothalamic and limbic areas. Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers various aspects of infant-directed agonistic responses, such as neglect, repulsion, and aggression. Thus, PeFAUcn3 neurons emerge as a dedicated circuit component controlling infant-directed neglect and aggression, providing a new framework to understand the positive and negative regulation of parenting in health and disease.

Neuroprotective Effect of Fructus broussonetiae on APP/PS1 Mice via Upregulation of AKT/ß-Catenin Signaling.

OBJECTIVE: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD). METHODS: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice. To further explore the mechanisms underlying FB's protective effect, PC-12 cells were treated with Aß25-35 in order to establish an in vitro model of AD. RESULTS: FB-treated mice showed improved learning and memory capacity on both the Morris water maze and object recognition tests. RNA-seq of hippocampal tissue from APP/PS1 mice showed that FB had effects on multiple signaling pathways, specifically decreasing cell apoptotic signaling and increasing AKT and ß-catenin signaling. Similarly, FB up-regulated both AKT and ß-catenin signaling in PC-12 cells pre-treated with Aß25-35, in which AKT positively regulated ß-catenin signaling. Further study showed that AKT promoted ß-catenin signaling via enhancing ß-catenin (Ser552) phosphorylation. Moreover, AKT and ß-catenin signaling inhibition both resulted in the attenuated survival of FB-treated cells, indicating the AKT/ß-catenin signaling is a crucial mediator in FB promoted cell survival. CONCLUSIONS: FB exerted neuroprotective effects on hippocampal cells of APP/PS1 mice, as well as improved cell viability in an in vitro model of AD. The protective actions of FB occurred via the upregulation of AKT/ß-catenin signaling.

Antidepressant-Like Effects of Chaihu Shugan Powder () on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis.

OBJECTIVE: To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively. RESULTS: Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats. CONCLUSION: CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia.

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

Highly efficient synthesis and monoamine oxidase B inhibitory profile of demethyleneberberine, columbamine and palmatine.

The biosynthesis of berberine alkaloids is thought to begin with the demethylation of berberine followed by methylation reactions to generate other type berberine alkaloids. This seemingly expeditious way to access berberine alkaloids has been stagnated for over half a century due to certain vexing synthetic problems, such as low isolated yield, complex operations and toxic reagents. We further investigated this bioinspired semi-synthesis strategy and significantly improved the synthetic efficacy, by providing a practical synthetic process for demethyleneberberine (DMB), columbamine and palmatine. Furthermore, we found that DMB (IC50, 9.06 µM) inhibited the activity of monoamine oxidase B (MAO-B), an enzyme that deaminates dopamine and is particularly involved in the pathology of Parkinson's disease. Besides, columbamine was able to decrease MAO-B activity by approximately 40%. These findings provide perquisites for further in vivo investigation to confirm the therapeutic potentiality of berberine alkaloids, DMB in particular.

Lei-gong-gen formula granule attenuates hyperlipidemia in rats via cGMP-PKG signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among the 56 nationalities in China. It is composed of three herbs, namely Centella asiatica (L.) Urb., Eclipta prostrata (L.) L., Smilax glabra Roxb. It has been widely used as health protection tea for many years to prevent cardiovascular and cerebrovascular diseases such as hyperlipidemia and hypertension. AIM OF THE STUDY: This study validated the lipid-lowering effect of LFG in a hyperlipidemia rat model. Then we employed network pharmacology and molecular biological approach to identify the active ingredients of LFG, corresponding targets, and its anti-hyperlipidemia mechanisms. MATERIALS AND METHODS: Hyperlipidemia rat model was established by feeding male Sprague-Dawley rats with high-fat diet for two weeks. LFG (two doses of 10 and 20 g/kg) was administered orally to hyperlipidemia rat model for 4 weeks, twice per day. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were monitored in rats pre and post-treatment. Hematoxylin-eosin staining was applied to observe the pathology and lipid accumulation of liver. We then performed network pharmacology analysis to predict the ingredients, their associated targets, and hyperlipidemia associated targets. Pathway analysis with significant genes was carried out using KEGG pathway. These genes and proteins intersectioned between compound targets and hyperlipidemia targets were further verified with samples from hyperlipidemia rats treated with LFG using Real-time RT-PCR and Western Blot. RESULTS: LFG attenuated hyperlipidemia in rat model, and this was characterized with decreased serum levels of TC, LDL-C, liver wet weight, and liver index. LFG alleviated the hepatic steatosis in hyperlipidemia rats. Network pharmacology analysis identified 53 bioactive ingredients from LFG formula (three herbs), which link to 765 potential targets. 53 hyperlipidemia associated genes were retrieved from public databases. There were 10 common genes between ingredients-targets and hyperlipidemia associated genes, which linked to 20 bioactive ingredients. Among these 10 genes, 3 of them were validated to be involved in LFG's anti-hyperlipidemia effect using Real-time RT-PCR, namely ADRB2 encoding beta-2 adrenergic receptor, NOS3 encoding nitric oxide synthase 3, LDLR encoding low-density lipoprotein receptor. The cGMP-PKG signaling pathway was enriched for hyperlipidemia after pharmacology network analysis with ADRB2, NOS3, and LDLR. Interestingly, expression of cGMP-dependent protein kinase (PKG) was downregulated in hyperlipidemia rat after LFG treatment. Molecular docking study further supported that ferulic acid, histidine, p-hydroxybenzoic acid, and linalool were potential active ingredients for LFG's anti-hyperlipidemia effect. LC-MS/MS analysis confirmed that ferulic acid and p-hydroxybenzoic acid were active ingredients of LFG. CONCLUSION: LFG exhibited the lipid-lowering effect, which might be attributed to downregulating ADRB2 and NOS3, and upregulating LDLR through the cGMP-PKG signaling pathway in hyperlipidemia rat. Ferulic acid and p-hydroxybenzoic acid might be the underlying active ingredients which affect the potential targets for their anti-hyperlipidemia effect.

An herbal formula inhibits STAT3 signaling and attenuates bone erosion in collagen-induced arthritis rats.

BACKGROUND: Receptor activator of NF-κB ligand (RANKL) facilitates differentiation of osteoclast precursors into osteoclasts, resulting in bone erosion in rheumatoid arthritis (RA) patients. Fibroblast-like synoviocytes (FLS) are the main cells for producing RANKL. Signal transducer and activator of transcription 3 (STAT3) signaling is activated in FLS of RA patients (RA-FLS), which has been linked to RANKL production. A two-herb formula (RL) comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos is traditionally used for treating RA in China. We have found that a standardized ethanolic extract of RL (RLE for short) alleviates bone erosion in collagen-induced arthritis (CIA) rats. PURPOSE: This study aimed to determine whether RLE inhibits RANKL production and osteoclastogenesis in cell and rat models, and to explore the involvement of the STAT3 pathway in this inhibition. STUDY DESIGN AND METHODS: A CIA rat model, interleukin-6/soluble interleukin-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS and a co-culture system (IL-6/sIL-6R-stimulated RA-FLS/peripheral blood mononuclear cells) were used to evaluate the effects of RLE. Micro-computed tomography analysis was used to observe bone erosion in CIA rats. Tartrate-resistant acid phosphatase staining was used to evaluate osteoclastogenesis. Western blotting and ELISA assays were employed to examine protein levels. RT-qPCR was used to detect mRNA levels. STAT3-over-activated RA-FLS were used to investigate the involvement of STAT3 signaling in the anti-osteoclastogenic effects of RLE. RESULTS: RLE alleviated bone erosion in joints of CIA rats. In both synovial tissues of CIA rats and IL-6/sIL-6R-stimulated RA-FLS, RLE downregulated the protein level of RANKL. In the co-culture system, RLE significantly and dose-dependently inhibited IL-6/sIL-6R-induced osteoclastogenesis. Mechanistic studies revealed that RLE lowered the protein level of phospho-STAT3 (Tyr705) in synovial tissues of CIA rats. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited the activation/phosphorylation of a STAT3 upstream kinase Janus kinase 2 (Tyr1007/1008) and STAT3 (Tyr705), decreased the nuclear localization of STAT3, lowered mRNA levels of STAT3-transcriptionally regulated genes IL-1ß and TNF-α. RLE's inhibitory effects on RANKL production in RA-FLS gradually decreased when IL-6/sIL-6R doses increased. Over-activation of STAT3 diminished the inhibitory effects of RLE on RANKL production in IL-6/sIL-6R-stimulated RA-FLS, and attenuated the anti-osteoclastogenic effects of RLE in the co-culture system. CONCLUSION: We, for the first time, demonstrated that suppressing STAT3 signaling contributes to the inhibition of RANKL production and osteoclastogenesis, and thereby supports the mechanisms responsible for the reduction in bone erosion in RLE-treated CIA rats. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug, and supports the notion that targeting STAT3 signaling is a viable strategy for managing bone erosion.

General characteristics, economic burden, causative drugs and medical errors associated with medical damage litigation involving severe cutaneous adverse drug reactions in China.

WHAT IS KNOWN AND OBJECTIVE: To investigate the general characteristics, economic burden, causative drugs and medical errors associated with litigation involving severe cutaneous adverse drug reactions (SCADRs) in China, with the aims of improving rational medication use and reducing the extent of damage from SCADRs. METHODS: This study analysed 150 lawsuit judgements involving SCADRs from 2005 to 2019, collected from China Judgments Online. RESULTS AND DISCUSSION: In total, 50% of lawsuits stemmed from SCADRs occurring in general hospitals. The average time elapsed from the date of occurrence of the SCADRs to the end of litigation procedures was 1055 days. Of the patients involved, 51% were female and more than two thirds (69%) were under 60 years old. The most common outcome of SCADRs was death (39%), followed by disabilities (30%). The average responsibility of the medical provider was 48 ± 29%. The average amount of compensation was $43 424. Of the cases studied, 51% of SCADRs were Stevens-Johnson syndrome or toxic epidermal necrolysis, which together accounted for 75% of cases with known clinical subtype. The overall average economic burden of SCADRs was $99 178, of which indirect costs made up the largest proportion (more than 60%). The most common causative drug groups were antimicrobial drugs (49%), Chinese patent medicine and Chinese herbal medicine (17%), and antipyretic analgesics (16%). Finally, 61% of medical errors were found to stem from violation of duty of care, 20% from violation of informed consent and 18% from violations related to the medical record writing and management system. WHAT IS NEW AND CONCLUSION: Severe cutaneous adverse drug reactions not only severely affect patient survival and quality of life, but also impose a heavy economic burden in terms of health care and societal costs. Medical providers should be better educated on strategies to reduce risk to patients and establish mechanisms of risk sharing and management.

Chrysoeriol ameliorates TPA-induced acute skin inflammation in mice and inhibits NF-κB and STAT3 pathways.

BACKGROUND: Chrysoeriol is a flavone found in diverse dietary and medicinal herbs such as Lonicerae Japonicae Flos (the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.). These herbs are commonly used for treating inflammatory diseases. Herbal extracts containing chrysoeriol have been shown to have anti-inflammatory effects and inhibit nuclear factor-kappa B (NF-κB) signaling. Some of these extracts can inhibit signal transducers and activators of transcription 3 (STAT3) signaling in cancer cells. PURPOSE: This study aimed to determine whether chrysoeriol has anti-inflammatory effects and whether NF-κB and STAT3 pathways are involved in the effects. STUDY DESIGN AND METHODS: A TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model and LPS-stimulated RAW264.7 cells were used to evaluate the effects of chrysoeriol. Griess reagent was used to measure the production of nitric oxide (NO). Western blot and enzyme-linked immunosorbent assays were employed to detect protein levels. RT-qPCR analyses were used to detect mRNA levels. Haematoxylin and eosin (H&E) staining was employed to examine the pathological conditions in animal tissues. RESULTS: In the mouse model, chrysoeriol ameliorated acute skin inflammation, evidenced by reduced ear thickness, ear weight and number of inflammatory cells in inflamed ear tissues. The compound lowered protein levels of phospho-p65 (Ser536), phospho-STAT3 (Tyr705), inducible nitric oxide synthases (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor α (TNF-α) in mouse swollen ears. In LPS-stimulated RAW264.7 cells, chrysoeriol also lowered levels of these proteins. In addition, chrysoeriol decreased the production of NO and prostaglandin E2; inhibited the phosphorylation of inhibitor of κB (Ser32), p65 (Ser536) and Janus kinase 2 (Tyr1007/1008); decreased nuclear localization of p50, p65 and STAT3; and down-regulated mRNA levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α that are transcriptionally regulated by NF-κB and STAT3 in the cell model. CONCLUSION: We for the first time demonstrated that chrysoeriol ameliorates TPA-induced ear edema in mice, and that inhibition of JAK2/STAT3 and IκB/p65 NF-κB pathways are involved in the anti-inflammatory effects of chrysoeriol. This study provides chemical and pharmacological justifications for the use of chrysoeriol-containing herbs in treating inflammatory diseases, and provides pharmacological groundwork for developing chrysoeriol as a novel anti-inflammatory agent.

Dynamic urinary metabolomics analysis based on UHPLC-Q-TOF/MS to investigate the potential biomarkers of blood stasis syndrome and the effects of Danggui Sini decoction.

Blood stasis syndrome (BSS) is one of the common syndromes in traditional Chinese medicine (TCM). It involves abnormal blood circulation, which can progress to produce many severe diseases. Danggui Sini decoction (DSD) is a classical TCM prescription frequently used to treat BSS by decreasing blood stasis and improving blood circulation. However, understanding of the therapeutic mechanism of DSD during the development of BSS is still limited, as the development of BSS is a slow dynamic process. Therefore, a dynamic urinary metabolomics analysis based on ultra-high-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UHPLC-Q-TOF/MS) combined with multivariate statistical analysis was used to explore the distinctive metabolic patterns of BSS development and the efficacy of DSD. The dynamic changes of endogenous metabolites over time revealed the progression of BSS and allowed the overall efficacy of DSD in rats with BSS to be evaluated. The effects of the DSD compatibilities were also explored. A total of 21 metabolites were identified during the development of BSS. They are involved in the metabolic pathways of tryptophan metabolism, phenylalanine metabolism, riboflavin metabolism, nicotinate and nicotinamide metabolism, pentose and glucuronate interconversions, histidine metabolism, steroid hormone biosynthesis, and starch and sucrose metabolism. A receiver operating characteristic (ROC) curve analysis showed that 10 metabolites with an area under the curve (AUC) value >0.9, which can be used as potential biomarkers for the diagnosis of BSS. In conclusion, a dynamic urinary metabolomics approach was applied to identify potential biomarkers of the development of BSS and to clarify the therapeutic mechanism of DSD in BSS. The results could provide a theoretical basis for further research on the therapeutic mechanism of DSD.

Optimized Complex Network Method (OCNM) for Improving Accuracy of Measuring Human Attention in Single-Electrode Neurofeedback System.

A neurofeedback system adjusting an individual's attention is an effective treatment for attention-deficit/hyperactivity disorder (ADHD). In current studies, an accurate measure of the level of human attention is one of the key issues that arouse much interest. This paper proposes a novel optimized complex network method (OCNM) for measuring an individual's attention level using single-electrode electroencephalography (EEG) signals. A time-delay embedding algorithm was used to reconstruct EEG data epochs into nodes of the OCNM network. Euclidean distances were calculated between each two nodes to decide edges of the network. Three key parameters influencing OCNM, i.e., delaying time, embedding dimension, and connection threshold, were optimized for each individual. The average degree and clustering coefficient of the constructed network were extracted as a feature vector and were classified into two patterns of concentration and relaxation using an LDA classifier. In the offline experiments of six subjects, the classification performance was tested and compared with an attention meter method (AMM) and an α + ß + δ + θ + R method. The experimental results showed that the proposed OCNM achieved the highest accuracy rate (80.67% versus 70.58% and 68.88%). This suggests that the proposed method can potentially be used for EEG-based neurofeedback systems with a single electrode.

[Regulatory effect of Shudihuang on expressions of BDNF/TrkB and NRG-3 in prefrontal cortex and striatum of ADHD model rats].

To observe the effect of Shudihuang on behaviors and expression of BDNF/TrkB and NRG-3 in prefrontal cortex and striatum of attention deficit hyperactivity disorder (ADHD) model rats. Thirty 4-week-old spontaneous hypertension rats (SHR) were randomly divided into model group, methylphenidate hydrochloride (MPH, 2 mg·kg⁻¹·d⁻¹) and Shudihuang group (2.4 g·kg⁻¹·d⁻¹). Another 10 Wistar-Kyoto (WKY) rats were selected as normal control group. The 0.5% CMC-Na solution was administered to model group and WKY rats (2 mL·kg⁻¹·d⁻¹). All of the rats were treated for 4 weeks. The open field test was performed at the 14th and 28th days after gavage, in order to evaluate the spontaneous and impulsive behaviors. Subsequently, gene and protein expressions of BDNF/TrkB and NRG-3 were tested by RT-qPCR and Western blot. Compared with model group, MPH and Shudihuang groups showed significant reduction in total distance, mean velocity and central distance in the open field test (P<0.05), and Shudihuang group displayed a shorter central distance than MPH group (P<0.05). RT-qPCR and Western blot analysis indicated that expressions of BDNF/TrkB and NRG-3 were lower in prefrontal cortex and striatum of SHR compared with WKY rats. Four weeks later after administration, both Shudihuang and MPH significantly elevated mRNA and protein expressions of BDNF/TrkB and NRG-3 (P<0.05).In conclusion, neurodevelopmental disorder mediated by BDNF/TrkB and NRG-3 was closely related with SHR rats' behaviors. Shudihuang may ameliorate the spontaneous and impulsive behaviors by up-regulating the expressions of BDNF/TrkB and NRG-3 and improving growth and maturation of neurons in SHR.

Chaihu-Shugan-San exerts an antidepressive effect by downregulating miR-124 and releasing inhibition of the MAPK14 and Gria3 signaling pathways.

Dysregulation of miR-124 has been reported to be involved in the pathophysiology of depression. Chaihu-Shugan-San, a traditional Chinese medicine, has antidepressive activity; however, the underlying mechanisms remain unclear. In this study, to generate a rodent model of depression, rats were subjected to a combination of solitary confinement and chronic unpredictable mild stress for 28 days. Rats were intragastrically administered Chaihu-Shugan-San (2.835 mL/kg/d) for 4 weeks, once a day. Real-time reverse-transcription quantitative polymerase chain reaction, miRNA microarray, western blot assay and transmission electron microscopy demonstrated that Chaihu-Shugan-San downregulated miR-124 expression and upregulated the mRNA and protein levels of mitogen-activated protein kinase 14 (MAPK14) and glutamate receptor subunit 3 (Gria3). Chaihu-Shugan-San also promoted synapse formation in the hippocampus. The open field test, sucrose consumption test and forced swimming test were used to assess depression-like behavior. After intragastric administration of Chaihu-Shugan-San, sucrose consumption increased, while the depressive behaviors were substantially reduced. Together, these findings suggest that Chaihu-Shugan-San exerts an antidepressant-like effect by downregulating miR-124 expression and by releasing the inhibition of the MAPK14 and Gria3 signaling pathways.