Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways.

Declining estrogen production in postmenopausal females causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. Although clinical drugs are currently available for the treatment of osteoporosis, sustained medication use is accompanied by serious side effects. Corydalis bungeana Herba, a famous traditional Chinese herb listed in the Chinese Pharmacopoeia Commission, constitutes various traditional Chinese Medicine prescriptions, which date back to thousands of years. One of the primary active components of C. bungeana Turcz. is Corynoline (Cor), a plant isoquinoline alkaloid derived from the Corydalis species, which possesses bone metabolism disease therapeutic potential. The study aimed at exploring the effects as well as mechanisms of Cor on osteoclast formation and bone resorption. TRAcP staining, F-actin belt formation, and pit formation were employed for assessing the osteoclast function. Western blot, qPCR, network pharmacology, and docking analyses were used for analyzing the expression of osteoclast-associated genes and related signaling pathways. The study focused on investigating how Cor affected OVX-induced trabecular bone loss by using a mouse model. Cor could weaken osteoclast formation and function by affecting the biological receptor activators of NF-κB and its ligand at various concentrations. Mechanistically, Cor inhibited the NF-κB activation, and the MAPKs pathway stimulated by RANKL. Besides, Cor enhanced the protein stability of the Nrf2, which effectively abolished the RANKL-stimulated ROS generation. According to an OVX mouse model, Cor functions in restoring bone mass, improving microarchitecture, and reducing the ROS levels in the distal femurs, which corroborated with its in vitro antiosteoclastogenic effect. The present study indicates that Cor may restrain osteoclast formation and bone loss by modulating NF-κB/MAPKs and Nrf2 signaling pathways. Cor was shown to be a potential drug candidate that can be utilized for the treatment of osteoporosis.

EMDR versus waiting list in individuals at clinical high risk for psychosis with post-traumatic stress symptoms: A randomized controlled trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) is highly prevalent in the individuals at clinical-high risk for psychosis (CHR). The aim of this study was to examine the efficacy and safety of Eye Movement Desensitization and Reprocessing (EMDR) in individuals at CHR with comorbid PTSD or subthreshold PTSD in a randomized controlled trial. METHODS: Fifty-seven individuals at CHR with PTSD or subthreshold PTSD formed the study sample. The eligible participants were randomly assigned to a 12 weeks EMDR treatment (N = 28) or a waiting list condition (WL, N = 29). The structured interview for psychosis risk syndrome (SIPS), the clinician administered post-traumatic stress disorder scale (CAPS) and a battery of self-rating inventories covering depressive, anxiety and suicidal symptoms were administered. RESULTS: Twenty-six participants in the EMDR group and all the participants in the WL group completed the study. The analyses of covariance revealed greater reduction of the mean scores on CAPS (F = 23.2, Partial η2 = 0.3, P < 0.001), SIPS positive scales (F = 17.8, Partial η2 = 0.25, P < 0.001) and all the self-rating inventories in the EMDR group than in the WL group. Participants in the EMDR group were more likely to achieve remission of CHR compared to those in the WL group at endpoint (60.7 % vs. 31 %, P = 0.025). CONCLUSIONS: EMDR treatment not only effectively improved traumatic symptoms, but also significantly reduced the attenuated psychotic symptoms and resulted in a higher remission rate of CHR. This study highlighted the necessity of adding a trauma-focused component to the present approach of early intervention in psychosis.

Cloning and expression analysis of HY5 transcription factor gene of safflower in response to light signal.

The flower of the safflower (Carthamus tinctorius L.) is a traditional Chinese medicine that can improve cerebral blood flow due to its enrichment in flavonoids. Light is one of the main environmental factors that affects safflower growth and flavonoid synthesis. Elongated hypocotyl 5 (HY5) plays an important role in plants' light signal transduction. However, no study of HY5 in safflower has been conducted. In this study, a 462-bp sequence of CtHY5 was successfully cloned. The expression pattern of CtHY5 in different safflower tissues and the expression patterns of CtHY5 and CtCHS1 in full-blooming flowers that were treated under different light intensities were studied. The subcellular localization and the overexpression of CtHY5 were carried out as well. CtHY5 has a DNA-binding region belonging to the basic leucine zipper transcription factor family. CtHY5 was specifically expressed in flowers. The expression level of CtHY5 first increased and then decreased with increasing light intensity, which was similar to the expression pattern of CtCHS1. The subcellular localization study was implemented in safflower protoplasts and the YFP fluorescence was observed in nucleus. The overexpression analysis initially verified the promotion effect of CtHY5 to the expression of CtCHS1 and the content of flavonoids.

Mechanism of platelet activation and potential therapeutic effects of natural drugs.

BACKGROUND: Cardiovascular disease is one of the most concerning chronic diseases in the world. Many studies have shown that platelet overactivation is a very important factor in the occurrence and development of cardiovascular diseases. At present, the widely used antiplatelet drugs have some defects, such as drug resistance and adverse reactions. PURPOSE: The purpose of this article is to summarize the main mechanisms and pathways of platelet activation, the main targets of antiplatelet aggregation, and the antiplatelet aggregation components of natural drugs and their mechanisms of action to provide new research ideas for the development and application of antiplatelet drugs. STUDY DESIGN AND METHODS: In this review, we systematically searched the PubMed, Google Scholar, Web of Science, and CNKI databases and selected studies based on predefined eligibility criteria. We then assessed their quality and extracted data. RESULTS: ADP, AA, THR, AF, collagen, SDF-1α, and Ca2+ can induce platelet aggregation and trigger thrombosis. Natural drugs have a good inhibitory effect on platelet activation. More than 50 kinds of natural drugs and over 120 kinds of chemical compounds, including flavonoids, alkaloids, saponins, terpenoids, coumarins, and organic acids, have significantly inhibited platelet activation activity. The MAPK pathway, cGMP-PKG pathway, cAMP-PKA pathway, PI3K-AKT pathway, PTK pathway, PLC pathway, and AA pathway are the main mechanisms and pathways of platelet activation. CONCLUSION: Natural drugs and their active ingredients have shown good activity and application prospects in anti-platelet aggregation. We hope that this review provides new research ideas for the development and application of antiplatelet drugs.

Study on the potential mechanism, therapeutic drugs and prescriptions of insomnia based on bioinformatics and molecular docking.

Insomnia is a very common disease worldwide. It seriously affects the quality of human life and even endangers health. Traditional Chinese medicine (TCM) has unique advantages in the intervention and treatment of insomnia. However, its underlying mechanism has yet to be elucidated. This study was performed to explore the potential biomarkers and mechanisms of insomnia, and treatment TCM and classical prescriptions. The gene microarray data of insomnia is downloaded and preprocessed. Differentially expressed genes (DEGs) and GO and KEGG enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed. Small molecule drugs for curing insomnia were identified using cMap and CTD databases. We searched the TCM corresponding to small molecule drugs and the classic prescriptions corresponding to TCM by the TCMSP database. We constructed a network of "ingredient-TCM-classic prescriptions". The molecular docking was performed to validate the screening results. We obtained a total of 124 DEGs, including 78 up-regulated genes, 46 down-regulated genes, 10 Hub genes and 3 key modules. A total of 125 significant GO entries and 15 significant KEGG were enriched (P < 0.05). The main biological processes involve neuronal apoptosis, autophagy, cell growth and apoptosis, etc. These signaling pathways may be involved in molecular regulatory mechanisms of insomnia, such as autophagy regulation, Alzheimer's disease, pathways to neurodegenerative diseases and neurotrophic factor signaling pathways. We identified 10 traditional Chinese medicines and 2 classical prescriptions of potential value. In addition, the molecular docking results indicated that small molecule ligands were nicely bound to the Hub gene, and the binding affinity ranged from -7.6 to -9.7 kcal/mol. This study provides a foundation for the clinical treatment of insomnia, explains the molecular mechanisms, and efficiently develops TCM and classical prescriptions.

Integrated metabolomics and transcriptome analysis on flavonoid biosynthesis in flowers of safflower (Carthamus tinctorius L.) during colour-transition.

Background: Safflower (Carthamus tinctorius L.), well known for its flower, is widely used as a dye and traditional Chinese medicine. Flavonoids, especially flavonoid glycosides, are the main pigments and active components. However, their biosynthesis is largely unknown. Interestingly, the colour of flowers in safflower changed from yellow to red during flower development, while much of the gene and chemical bases during colour transition are unclear. Methods: In this research, widely targeted metabolomics and transcriptomics were used to elucidate the changes in flavonoid biosynthesis from the gene and chemical points of view in flowers of safflower during colour transition. The screening of differential metabolites depended on fold change and variable importance in project (VIP) value. Differential expressed genes (DEGs) were screened by DESeq2 method. RT-PCR was used to analyse relative expressions of DEGs. Results: A total of 212 flavonoid metabolites, including hydroxysafflor yellow A, carthamin and anthocyanins, were detected and showed a large difference. The candidate genes of glycosyltransferases and flavonoid hydroxylase that might participate in flavonoid glycoside biosynthesis were screened. Ten candidate genes were screened. Through integrated metabolomics and transcriptome analysis, a uridine diphosphate glucose glycosyltransferase gene, CtUGT9 showed a significant correlation with flavonoid glycosides in safflower. In addition, expression analysis showed that CtUGT9 was mainly expressed in the middle development of flowers and was significantly upregulated under MeJA treatment. Our results indicated that CtUGT9 might play an important role in flavonoid glycoside biosynthesis during colour-transition in safflower.

Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor, and almost half of the patients carrying EGFR-driven tumor with PTEN deficiency are resistant to EGFR-targeted therapy. EGFR amplification and/or mutation is reported in various epithelial tumors. This series of studies aimed to identify a potent compound against EGFR-driven tumor. We screened a chemical library containing over 600 individual compounds purified from Traditional Chinese Medicine against GBM cells with EGFR amplification and found that cinobufagin, the major active ingredient of Chansu, inhibited the proliferation of EGFR amplified GBM cells and PTEN deficiency enhanced its anti-proliferation effects. Cinobufagin also strongly inhibited the proliferation of carcinoma cell lines with wild-type or mutant EGFR expression. In contrast, the compound only weakly inhibited the proliferation of cancer cells with low or without EGFR expression. Cinobufagin blocked EGFR phosphorylation and its downstream signaling, which additionally induced apoptosis and cytotoxicity in EGFR amplified cancer cells. In vivo, cinobufagin blocked EGFR signaling, inhibited cell proliferation, and elicited apoptosis, thereby suppressing tumor growth in both subcutaneous and intracranial U87MG-EGFR xenograft mouse models and increasing the median survival of nude mice bearing intracranial U87MG-EGFR tumors. Cinobufagin is a potential therapeutic agent for treating malignant glioma and other human cancers expressing EGFR.

Integrated Metabolomics and Transcriptome Analysis of Flavonoid Biosynthesis in Safflower (Carthamus tinctorius L.) With Different Colors.

Safflower is widely used in dying and in traditional medicine, and C-glucosylquinochalcones are the main metabolic species in the red color of safflower. Various safflower cultivars have flowers with different colors. However, the metabolic and transcriptional differences among safflower cultivars with different-colored flowers and the genes participating in C-glucosylquinochalcone biosynthesis are largely unknown. To provide insights on this issue, we performed integrated metabolomics and transcriptome analyses on the flavonoid biosynthesis of flowers of different colors in safflower (white-W, yellow-Y, light red-LR, and deep red-DR). The metabolic analysis showed that flavonoid metabolites showed great differences among the different colors of safflower. More flavonoid metabolic species were detected in Y and W, while C-glucosylquinochalcones were not detected in W. The content of C-glucosylquinochalcones increased with increasing color. Transcriptional analysis showed that most of the annotated flavonoid biosynthesis genes were significantly increased in W. The expression of genes related to flavonoid biosynthesis decreased with increasing color. We analyzed the candidate genes associated with C-glucosylquinochalcones, and an integration of the metabolic and transcriptional analyses indicated that the differential expression of the chalcone synthase (CHS) gene is one of the main reasons for the difference in flavonoid species and content among the different colors of safflower. Combined with the expression pattern analysis, these results indicated that HH_035319, HH_032689, and HH_018025 are likely involved in C-glucosylquinochalcones biosynthesis. In addition, we found that their expression showed greatly increased after the methyl jasmonate (MeJA) treatment. Therefore, HH_035319, HH_032689, and HH_018025 might participate in C-glucosylquinochalcone biosynthesis, which ultimately leads to the red color in safflower.

Integrated metabolomics and transcriptome analysis on flavonoid biosynthesis in safflower (Carthamus tinctorius L.) under MeJA treatment.

BACKGROUND: Safflower (Carthamus tinctorius L.) is an important cash crop, of which the dried tube flower is not only an important raw material for dyes and cosmetics but also an important herb widely used in traditional Chinese medicine. The pigment and bioactive compounds are composed of flavonoids (mainly quinone chalcones), and studies have reported that MeJA can promote the biosynthesis of quinone chalcones, but the mechanism underlying the effect of MeJA in safflower remains unclear. Here, we attempt to use metabolomics and transcriptome technologies to analyse the molecular mechanism of flavonoid biosynthesis under MeJA treatment in safflower. RESULTS: Based on a UHPLC-ESI-MS/MS detection platform and a self-built database (including hydroxysafflor yellow A, HSYA), a total of 209 flavonoid metabolites were detected, and 35 metabolites were significantly different after treatment with MeJA. Among them, 24 metabolites were upregulated upon MeJA treatment, especially HSYA. Eleven metabolites were downregulated after MeJA treatment. Integrated metabolomics and transcriptome analysis showed that MeJA might upregulate the expression of upstream genes in the flavonoid biosynthesis pathway (such as CHSs, CHIs and HCTs) and downregulate the expression of downstream genes (such as F3Ms, ANRs and ANSs), thus promoting the biosynthesis of quinone chalcones, such as HSYA. The transcription expressions of these genes were validated by real-time PCR. In addition, the promoters of two genes (CtCHI and CtHCT) that were significantly upregulated under MeJA treatment were cloned and analysed. 7 and 3 MeJA response elements were found in the promoters, respectively. CONCLUSIONS: MeJA might upregulate the expression of the upstream genes in the flavonoid biosynthesis pathway and downregulate the expression of the downstream genes, thus promoting the biosynthesis of quinone chalcones. Our results provide insights and basic data for the molecular mechanism analysis of flavonoid synthesis in safflower under MeJA treatment.

Transcriptome analysis of flavonoid biosynthesis in safflower flowers grown under different light intensities.

BACKGROUND: Safflower (Carthamus tinctorius L.) is a domesticated species with a long history of cultivation and widespread distribution across the globe, and light plays an important role in controlling its distribution boundary. Flowers from safflower have been widely used in traditional Chinese medicine because of their ability to improve cerebral blood flow. Flavonoids are the main active compounds in safflower and have many pharmacological effects. In this study, we aimed to explore the relationship between different light intensities and flavonoid biosynthesis in safflower flowers cultivated in greenhouse. METHODS: The transcriptome of safflower flowers grown under different light intensities were sequenced through BGISEQ-500 platform. After assembled and filtered, Unigenes were annotated by aligning with seven functional databases. Differential expression analysis of two samples was performed with the DEseq2 package. Differentially expressed genes (DEGs) related with flavonoids biosynthesis were analyzed by Real-time PCR (RT-PCR). Flavonoids accumulation in flowers were determined by high performance liquid chromatography and spectrophotometer. RESULTS: Transcriptome analysis of safflower flowers cultivated under different light intensities was performed. A total of 99.16 Gb data were obtained, and 78,179 Unigenes were annotated. Among the DEGs, 13 genes were related to flavonoid biosynthesis. The differential expressions of seven key genes were confirmed by RT-PCR. In addition, the levels of some flavonoids were measured in safflower flowers grown under different light intensities. CtHCT3 gene expression showed a significantly negative correlation with kaempferol content in safflower grown under different light intensities. CONCLUSION: Our results strongly suggested that the reduction in light intensity in a suitable range promoted flavonoid biosynthesis in safflower flowers. We suggest that the expressions of HCT genes played an important role in flavonoid accumulation in safflower flowers. Our study lays a foundation for further research on the effects of light on flavonoid biosynthesis in safflower.

Effect of intervention on osteoporosis related knowledge and behavior in city residents / 上海预防医学

Objective To evaluate the impact of comprehensive intervention mode on osteoporosis related knowledge and behavior among city residents aged over 40-year-old and to provide reference for osteoporosis prevention and treatment. Methods Health education including self-management of osteoporosis was conducted among Chongqing city residents aged over 40-year-old for 4 consecutive months.All the subjects were asked to fill out the questionnaire during face-to-face interview before and after the intervention.The changes in knowledge and daily life style were tested by Chi-square test. Results The residents surveyed were 2 028 before the intervention and 1 986 after the intervention.After the intervention, the proportion of awareness was significantly higher (P < 0.01) than that before the intervention in the following: features of osteoporosis(33.23% vs 18.49%), sensitive population of osteoporosis(10.52% vs 3.75%), balanced diet to prevent osteoporosis (23.82% vs 11.09%), bone health supplements (51.06% vs 32.84%), recommended daily calcium intake for postmenopausal women and older people (34.89% vs 13.91%).After the intervention, the proportions of residents who never drink milk and its products, and never eat beans and their products were decreased significantly (13.49% vs 23.09%, and 4.94% vs 7.00%, P < 0.01).The proportion of residents who take average more than 30 minutes daily outdoor activity under sunlight was increased significantly after the intervention (64.25% vs 59.27%, P < 0.01).The proportion of residents preferring salty food was decreased significantly after the intervention (8.26% vs 14.89%, P < 0.01). Conclusion The comprehensive intervention mode of health education in combination with traditional and new media as well as health self-management is a cost-effective prevention measure for osteoporosis, which can improve the osteoporosis cognitive level of middle-aged and senile people and the development of good behavior.

Impact of childhood trauma on sensory gating in patients with first-episode schizophrenia.

BACKGROUND: Childhood trauma (CT) has been found to contribute to the onset of schizophrenia and auditory sensory gating deficit is a leading endophenotype for schizophrenia. However, the association between the CT and sensory gating in first-episode schizophrenia remains elusive. METHODS: Fifty-six patients and 49 age and sex-matched healthy controls were assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) for CT and Positive and Negative Syndrome Scale (PANSS) for symptoms severity. Sensory gating was tested using the modified paradigm, perceived spatial separation-induced prepulse inhibition (PSS-PPI), and the perceived spatial co-location PPI (PSC-PPI or classical PPI). RESULTS: Comparing with healthy controls, the patients had significantly higher score on sexual abuse (t = 2.729, p < 0.05), lower PSS- PPI, % (ISI = 120 ms and ISI = 60 ms) (t = - 3.089, - 4.196, p < 0.05). Univariate analysis revealed the absence of a significant correlation among CT, PPI paradigms and symptoms. However, multiple linear regression analyses demonstrated the CTQ-SF total was negatively associated with PSS PPI (ISI = 120 ms) (p = 0.018). CONCLUSION: The current study illustrates that the impact of CT on sensory gating in patients with first-episode schizophrenia, and thus we conclude that CT may be a risk factor to the occurrence of schizophrenia through its impact on sensory gating.

An in Vitro Study on the Effect of Combined Treatment with Photodynamic and Chemical Therapies on Candida albicans.

Candida albicans is the most commonly encountered human fungal pathogen, and it is traditionally treated with antimicrobial chemical agents. The antimicrobial effect of these agents is largely weakened by drug resistance and biofilm-associated virulence. Enhancement of the antimicrobial activity of existing agents is needed for effective candidiasis treatment. Our aim was to develop a therapy that combined biofilm disruption with existing antimicrobial agents. Photodynamic therapy (PDT) utilizing curcumin and blue light was tested as an independent therapy and in combination with fluconazole treatment. Viability assays and morphology analysis were used to assess the effectiveness of C. albicans treatment. Results showed that fluconazole treatment decreased the viability of planktonic C. albicans, but the decrease was not as pronounced in adherent C. albicans because its biofilm form was markedly more resistant to the antimicrobiotic. PDT effectively eradicated C. albicans biofilms, and when combined with fluconazole, PDT significantly inhibited C. albicans to a greater extent. This study suggests that the addition of PDT to fluconazole to treat C. albicans infection enhances its effectiveness and can potentially be used clinically.

[Correlation Study on Risk Factors and CM Symptoms in Postmenopausal Osteoporosis].

Objective To observe the correlation between risk factors and symptoms of Chinese medicine (CM) in postmenopausal osteoporosis (OP) of females aged between 40 and 65. Methods Registry method was used in this study. Risk factors and information on symptoms of CM collected from 1 823 OP high risk females (40 -65 years old) in Dongcheng District of Beijing and Xuhui District of Shanghai (collected in our previous research). Meanwhile, Cox proportional hazard model was also a- dopted to conduct single-factor and multiple-factor analyses. Risk factors and symptoms of CM were screened and analyzed. Results A total of 1 498 subjects attended follow-up surveys, with the response rate of 82.17%. Of them, 52 had brittle fracture. In Cox single-factor analysis, when taking the time for occurrence of postmenopausal OP as the outcome variable, average age (RR = 1. 083, P = 0. 003 ) , whether menopause (RR = 5. 462, P = 0. 004), average menopausal year (RR = 1. 060, P = 0. 010) , menopausal year ≤10 years (RR =4. 890,P =0. 008), menopausal year >10 year (RR =7. 720,P = 0. 001) , delivery times ≤3 times (RR =5. 870, P =0. 003), dizziness (RR =3. 037, P =0. 001) , spasm of lower limbs (RR =2. 315, P =0. 003) , reduced bone mass in bone mass density (BMD) diagnosis (RR = 2. 376, P =0. 008) , ß >0 and RR >1 in BMD diagnosis (RR =2. 801 ,P =0. 013) indicated they were risk factors for postmenopausal OP fracture. When taking BMD diagnosis, age, menopausal year, delivery times, dizziness, and spasm of lower limbs in multiple-factor analysis, menopausal year <10 years (RR =3. 257,P =0. 032) and dizziness (RR =2. 655,P =0. 005) were associated variables. Conclusion Dizziness and menopausal years were most important factors of OP fracture, and dizziness could be taken as symptoms of CM in early predicting occurrence of OP fracture.

Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial.

OBJECTIVES: An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL. METHODS: Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points. RESULTS: Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ = 4.010, P = 0.045) and menstrual resumption (χ = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups. CONCLUSIONS: Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).

Clinical effect of Kudiezi injection on renal function based on propensity score.

To explore the effect of Kudiezi injection on renal function in the real world, in order to provide the basis for the clinical medication safety. Patient aged between 18-80 were selected from 18 large hospitals information system (HIS) databases established by clinical research institute for basic traditional Chinese medicine of China academy of Chinese medical sciences. The patients who were treated with Kudiezi injection (24 225 cases) were defined as the exposed group, whereas those who were not treated with Kudiezi injection (14,191 cases) were defined as the non-exposed group. The propensity score method was used to balance the confounding factors. Classic logistic regression, GBM weighted propensity score logistic regression, GBM propensity score weighted logistic regression with covariate and sensitivity analysis were adopted to study the effect of Kudiezi injection on renal function. The results showed no significant difference in the possibility in abnormality in serum creatinine (Scr) (P = 0.940, 0.679, 0.834) and urea nitrogen (BUN) (P = 0, 0.045, 0.164) between both groups. Therefore, the existing data indicated no damage of Kudiezi injection on renal function. Because this study is a retrospective study based on the real world, there may be unknown confounding factors and potential bias. Therefore, further studies shall be conducted to monitor whether Kudiezi injection causes damage on renal function, in order to ensure the clinical medication safety.

[Effects of tobacco garlic crop rotation and intercropping on tobacco yield and rhizosphere soil phosphorus fractions].

A field plot experiment was conducted to investigate the tobacco yield and different forms of soil phosphorus under tobacco garlic crop rotation and intercropping patterns. The results showed that compared with tobacco monoculture, the tobacco yield and proportion of middle/high class of tobacco leaves to total leaves were significantly increased in tobacco garlic crop rotation and intercropping, and the rhizosphere soil available phosphorus contents were 1.3 and 1.7 times as high as that of tobacco monoculture at mature stage of lower leaf. For the inorganic phosphorus in rhizosphere and non-rhizosphere soil in different treatments, the contents of O-P and Fe-P were the highest, followed by Ca2-P and Al-P, and Ca8-P and Ca10-P were the lowest. Compared with tobacco monoculture and tobacco garlic crop intercropping, the Ca2-P concentration in rhizosphere soil under tobacco garlic crop rotation at mature stage of upper leaf, the Ca8-P concentration at mature stage of lower leaf, and the Ca10-P concentration at mature stage of middle leaf were lowest. The Al-P concentrations under tobacco garlic crop rotation and intercropping were 1.6 and 1.9 times, and 1.2 and 1.9 times as much as that under tobacco monoculture in rhizosphere soil at mature stages of lower leaf and middle leaf, respectively. The O-P concentrations in rhizosphere soil under tobacco garlic crop rotation and intercropping were significantly lower than that under tobacco monoculture. Compared with tobacco garlic crop intercropping, the tobacco garlic crop rotation could better improve tobacco yield and the proportion of high and middle class leaf by activating O-P, Ca10-P and resistant organic phosphorus in soil.

Inhibition of autophagy augments apoptosis in human oral squamous cell carcinoma under nutrient depletion.

There has been little research conducted regarding autophagy in oral squamous cell carcinoma (OSCC). Given the prevalence of oral cancers which are OSCC and the severe side effects of current treatments, there is a pressing need to develop effective alternative therapies. In this study, we have endeavored to explore the biological characteristics of oral squamous cell carcinoma cell line KB cells, in particular with regard to the role played by autophagy in their survival. Autophagy was activated by nutrient depletion via culturing cells in Earle's balanced salts (EBSS) and was measured via indices relating to Beclin 1, microtubule-associated protein light chain 3 (MAPLC3, LC3), p62, and Green fluorescent protein-light chain 3 plasmid transfection (GFP-LC3). Cell death and apoptosis induced by nutrient depletion was measured using both MTT assay and flow cytometry (FCM). Compared to initial levels at 0 h, Beclin 1 density in EBSS-treated cells was found to have increased at 6, 12, and 18 h in a time-dependent manner and was found to have subsequently declined at 24 and 48 h. p62 levels, LC3-II/LC3-I ratio, and GFP-LC3 levels increased at 6, 12, 18, 24, and 48 h in a time-dependent manner. 3-methyladenine (3-MA) was found to inhibit autophagy and the expression of Beclin 1 and significantly enhanced nutrient depletion-induced apoptosis and death. We concluded that nutrient depletion enhances OSCC cell autophagy in time-course patterns and that the inhibition of autophagy augments apoptosis in OSCC cells. We also deduced that Beclin 1 takes part in the development and progression of autophagy, potentially playing an important role in the crosstalk between apoptosis and autophagy in OSCC cells. These findings suggest that nutrient depletion may be an effective way to explore autophagy and that autophagy inhibitors should be investigated as a potential novel agent for the adjuvant treatment of human OSCC.

Clinical effect of Kudiezi injection on renal function based on propensity score / 中国中药杂志

To explore the effect of Kudiezi injection on renal function in the real world, in order to provide the basis for the clinical medication safety. Patient aged between 18-80 were selected from 18 large hospitals information system (HIS) databases established by clinical research institute for basic traditional Chinese medicine of China academy of Chinese medical sciences. The patients who were treated with Kudiezi injection (24 225 cases) were defined as the exposed group, whereas those who were not treated with Kudiezi injection (14,191 cases) were defined as the non-exposed group. The propensity score method was used to balance the confounding factors. Classic logistic regression, GBM weighted propensity score logistic regression, GBM propensity score weighted logistic regression with covariate and sensitivity analysis were adopted to study the effect of Kudiezi injection on renal function. The results showed no significant difference in the possibility in abnormality in serum creatinine (Scr) (P = 0.940, 0.679, 0.834) and urea nitrogen (BUN) (P = 0, 0.045, 0.164) between both groups. Therefore, the existing data indicated no damage of Kudiezi injection on renal function. Because this study is a retrospective study based on the real world, there may be unknown confounding factors and potential bias. Therefore, further studies shall be conducted to monitor whether Kudiezi injection causes damage on renal function, in order to ensure the clinical medication safety.

[Analysis of questionable allergic factors to kudiezi injection--nested case control study using hospital information system data].

This study aims to assess if adverse drug reactions (ADRs) to Kudiezi injection are allergic in origin. Hospital information system (HIS) data from 18 hospitals in China were used to carry out a nested case control design study. Included were patients who received dexamethasone for suspected allergic reactions after receiving Kudiezi injection. These were compared with non-allergic reaction people. Single factor logistic regression and multiple factor logistic regression were used to analyze data. Condition on admission, allergic history, dosage, disease status and drug combinations were taken into account in cases of suspected allergic reactions. After analysis in two subgroups we found that the condition on solvents had a significant effect, P values were 0.005 5 and < 0.000 1 on suspected cases of allergic reactions. For the first subgroup analysis, we found using other eight injections at the same time as Kudiezi injection could be risk factors in suspected cases of allergic reactions. For the second subgroup analysis combining using mannitol or fructose could increase risks. Based on this current research, condition on admission as well as the concomitant use of some other drugs may be the risk factors in suspected cases of allergic reactions. However, further research for verification is required. This study can provide guidance for safe clinical practice in using Kudiezi injection.