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In 2023, the U.S. Food and Drug Administration has approved 55 novel medications, consisting of 17 biologics license applications and 38 new molecular entities. Although the biologics license applications including antibody and enzyme replacement therapy set a historical record, the new molecular entities comprising small molecule drugs, diagnostic agent, RNA interference therapy and biomacromolecular peptide still account for over 50 % of the newly approved medications. The novel and privileged scaffolds derived from drugs, active molecules and natural products are consistently associated with the discovery of new mechanisms, the expansion of clinical indications and the reduction of side effects. Moreover, the structural modifications based on the promising scaffolds can provide the clinical candidates with the improved biological activities, bypass the patent protection and greatly shorten the period of new drug discovery. Therefore, conducting an appraisal of drug approval experience and related information will expedite the identification of more potent drug molecules. In this review, we comprehensively summarized the pertinent information encompassing the clinical application, mechanism, elegant design and development processes of 28 small molecule drugs, and expected to provide the promising structural basis and design inspiration for pharmaceutical chemists.
Subject(s)
Drug Approval , United States Food and Drug Administration , Humans , United States , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Molecular StructureABSTRACT
Objective: To investigate the effects of photobiomodulation therapy (PBMT) on hard tissue healing in rat maxillary first molar extraction sockets. Methods: A total of 20 male Wistar rats were used in the study. The right extraction sockets were irradiated with a Ga-Al-As laser (500 mW, 980 nm) for 51.7 J/cm2 every 24 h for 7 days, while the left sockets served as controls. Rats were sacrificed on days 3, 7, 14, and 28 after tooth extraction, and microcomputed tomography (CT) analysis, histopathological evaluation, and enzyme-linked immunosorbent assay (ELISA) were conducted at different time points. Results: Micro-CT analysis showed that the percentage of bone volume/tissue volume (TV) and bone mineral density were significantly higher in the experimental group compared to the control group on day 28 (p < 0.05). Histopathological evaluation revealed that PBMT promoted new bone formation and accelerated bone remodeling. ELISA demonstrated a significant increase in alkaline phosphatase expression in the laser sides on days 7 and 14 (p < 0.05). Conclusions: One application postextraction followed by seven consecutive daily applications of PBMT can effectively promote hard tissue healing in rat maxillary first molar extraction sockets.
Subject(s)
Low-Level Light Therapy , Rats , Male , Animals , Rats, Wistar , X-Ray Microtomography , Low-Level Light Therapy/methods , Tooth Socket , Tooth ExtractionABSTRACT
Achieving carbon neutrality in the chemical industry necessitates a green and efficient transformation. Working together, industry and academia hold the key to developing clean chemical processes, which is crucial.
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PURPOSE: The purpose of this study was to determine whether metformin (MF) could alleviate the expresssion of reactive oxygen species (ROS) and improve the osteogenic ability of bone marrow mesenchymal stem cells derived from diabetic rats (drBMSCs) in vitro, and to evaluate the effect of MF on the ectopic osteogenesis of drBMSCs in a nude mouse model in vivo. METHODS: BMSCs were extracted from normal and diabetic rats. In vitro, a cell viability assay (Cell Counting Kit-8), tests of alkaline phosphatase (ALP) activity, and western blot analysis were first used to determine the cell proliferation and osteogenic differentiation of drBMSCs that were subjected to treatment with different concentrations of MF (0, 50, 100, 200, 500 µM). The cells were then divided into 5 groups: (1) normal rat BMSCs (the BMSCs derived from normal rats group), (2) the drBMSCs group, (3) the drBMSCs + Mito-TEMPO (10 µM, ROS scavenger) group, (4) the drBMSCs + MF (200 µM) group, and (5) the drBMSCs + MF (200 µM) + H2O2 (50 µM, ROS activator) group. Intracellular ROS detection, a senescence-associated ß-galactosidase assay, ALP staining, alizarin red staining, western blotting, and immunofluorescence assays were performed to determine the effects of MF on oxidative stress and osteogenic differentiation in drBMSCs. In vivo, the effect of MF on the ectopic osteogenesis of drBMSCs was evaluated in a nude mouse model. RESULTS: MF effectively reduced ROS levels in drBMSCs. The cell proliferation, ALP activity, mineral deposition, and osteogenic-related protein expression of drBMSCs were demonstrably higher in the MF-treated group than in the non-MF-treated group. H2O2 inhibited the effects of MF. In addition, ectopic osteogenesis was significantly increased in drBMSCs treated with MF. CONCLUSIONS: MF promoted the proliferation and osteogenic differentiation of drBMSCs by inhibiting the oxidative stress induced by diabetes and enhenced the ectopic bone formation of drBMSCs in nude mice.
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DCN1, a co-E3 ligase, interacts with UBC12 and activates cullin-RING ligases (CRLs) by catalyzing cullin neddylation. Although DCN1 has been recognized as an important therapeutic target for human diseases, its role in the cardiovascular area remains unknown. Here, we first found that DCN1 was upregulated in isolated cardiac fibroblasts (CFs) treated by angiotensin (Ang) II and in mouse hearts after pressure overload. Then, structure-based optimizations for DCN1-UBC12 inhibitors were performed based on our previous work, yielding compound DN-2. DN-2 specifically targeted DCN1 at molecular and cellular levels as shown by molecular modeling studies, HTRF, cellular thermal shift and co-immunoprecipitation assays. Importantly, DN-2 effectively reversed Ang II-induced cardiac fibroblast activation, which was associated with the inhibition of cullin 3 neddylation. Our findings indicate a potentially unrecognized role of DCN1 inhibition for anticardiac fibrotic effects. DN-2 may be used as a lead compound for further development.
Subject(s)
Antifibrotic Agents , Drug Discovery , Enzyme Inhibitors , Fibrosis , Heart Diseases , Intracellular Signaling Peptides and Proteins , Pyrimidines , Ubiquitin-Conjugating Enzymes , Animals , Male , Mice , Rats , Antifibrotic Agents/chemistry , Antifibrotic Agents/pharmacology , Cullin Proteins/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Fibroblasts/drug effects , Fibroblasts/pathology , Fibrosis/drug therapy , Fibrosis/metabolism , Fibrosis/pathology , Heart Diseases/drug therapy , Heart Diseases/metabolism , Heart Diseases/pathology , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Mice, Inbred C57BL , NEDD8 Protein/metabolism , Pyrimidines/chemistry , Rats, Sprague-Dawley , Ubiquitin-Conjugating Enzymes/antagonists & inhibitors , UbiquitinsABSTRACT
BACKGROUND: Concentrated growth factor (CGF) is a third-generation platelet concentrate product; the major source of growth factors in CGF is its extract; however, there are few studies on the overall effects of the extract of CGF (CGF-e). The aim of this study was to investigate the effect and mechanism of CGF-e on MC3T3-E1 cells in vitro and to explore the effect of combination of CGF-e and bone collagen (Bio-Oss Collagen, Geistlich, Switzerland) for bone formation in cranial defect model of rats in vivo. METHODS: The cell proliferation, ALP activity, mineral deposition, osteogenic-related gene, and protein expression were evaluated in vitro; the newly formed bone was evaluated by histological and immunohistochemical analysis through critical-sized cranial defect rat model in vivo. RESULTS: The cell proliferation, ALP activity, mineral deposition, osteogenic-related gene, and protein expression of CGF-e group were significantly increased compared with the control group. In addition, there was significantly more newly formed bone in the CGF-e + bone collagen group, compared to the blank control group and bone collagen only group. CONCLUSIONS: CGF-e activated the PI3K/AKT signaling pathway to enhance osteogenic differentiation and mineralization of MC3T3-E1 cells and promoted the bone formation of rat cranial defect model.
Subject(s)
Osteogenesis , Proto-Oncogene Proteins c-akt , Animals , Bone Regeneration , Intercellular Signaling Peptides and Proteins/genetics , Osteoblasts , Phosphatidylinositol 3-Kinases/genetics , Plant Extracts , Proto-Oncogene Proteins c-akt/genetics , RatsABSTRACT
OBJECTIVE: To analyze the genotypes and the hematological phenotypic characteristics of α-thalassemia in different areas of Fujian and to evaluate the values of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hemoglobin (Hb), RBC distribution width/red blood cell (RDW/RBC) for screening α-thalassemia in this area. METHODS: The Gap-PCR assay was applied for detecting 3 common deletional mutations of patients with α-thalassemia, and the reverse dot-blot (RDB) assay was adopted to detect the foci of 3 common non-deletional gene mutations.Then,the hematological parameters of individuals with α-thalassemia were analyzed. Finally, the optimal cut-off value in hematological indexes for screening α-thalassemia were determined by the ROC curve. RESULTS: Altogether 16 types of gene mutations were found in 772 patients with α-thalassemia. Among them, the -SEA/αα deletion mutation was the most common which was observed in 521 cases(67.49%). Compared with the control group, the differences in MCV, MCH, and Hb were statistically significant between the patients of the same sex but no same type. In male groups, the RDW/RBC ratio was statistically significant in individuals of light type and HbH disease as compared with the healthy control group. But in female groups, the statistical different of RDW/RBC ratio was found between only HbH disease group and control group. MCV<81.25 fl, MCH<27.30 pg, Hb(male)<128.5 g/L, and Hb(female) <123.5 g/L, with the highest specificity and the highest sensitivity, were the best cut-off points for screening α-thalassemia in the laboratory. CONCLUSION: Due to the difference of regional heterogeneity and hospital equipment environment, the different laboratories need to establish cut-off value for screening α-thalassemia suitable for its local region. In future, our laboratory can use MCV<81.25 fl, MCH<27.30 pg, Hb(male)<128.5 g/L, and Hb(female) <123.5 g/L for value for clinical screening, of α-thalassemia.
Subject(s)
alpha-Thalassemia , China , Erythrocyte Indices , Female , Genotype , Humans , Male , Mass ScreeningABSTRACT
OBJECTIVE: To observe the clinical efficacy of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period. METHODS: Ninety patients with periarthritis who met the inclusion criteria were randomly divided into a control group 1, a control group 2 and an observation group, 30 cases in each group. Warm acupuncture was applied in the control group 1 (Jianzhen (SI 9), Jianyu (LI 15), Jianliao (TE 14), etc were selected), yoga posture method was applied in the control group 2, warm acupuncture combined with yoga posture method were given in the observation group, the treatment was given once a day, 10 times as a course with 2 days between courses and continuous for 2 courses. After 2 courses of treatment, the shoulder joint pain score and shoulder function grading were used to evaluate the clinical efficacy, and the clinical efficacy was observed. RESULTS: â The pain scores of the three groups were significantly lower after treatment (all P<0.01), and scores in the observation group was better than that in the control group 1 and the control group 2 (P<0.05, P<0.01). There was no significant difference between the control group 1 and the control group 2 (P>0.05). â¡After treatment, the functional classification of shoulder joints were significantly improved in the three groups (all P<0.01), and the functional classification of shoulder joint in the observation group and the control group 2 were better than that in the control group 1 (P<0.01, P<0.05). There was no significant difference between the observation group and the control group 2 (P>0.05). â¢After 2 courses of treatment, the effective rate of the observation group was 86.7% (26/30), which was better than 70.0% (21/30) in the control group 1 and 76.7% (23/30) in the control group 2 (both P<0.05). CONCLUSION: Warm acupuncture combined with yoga posture method can effectively relieve shoulder pain and improve dysfunction. The clinical comprehensive effect is better than simple acupuncture and yoga posture method.
Subject(s)
Acupuncture Therapy , Periarthritis , Yoga , Acupuncture Points , Humans , Periarthritis/therapy , Posture , Treatment OutcomeABSTRACT
Plants have evolved sophisticated genetic networks to regulate iron (Fe) homeostasis for their survival. Several classes of plant hormones including jasmonic acid (JA) have been shown to be involved in regulating the expression of iron uptake and/or deficiency-responsive genes in plants. However, the molecular mechanisms by which JA regulates iron uptake remain unclear. In this study, we found that JA negatively modulates iron uptake by downregulating the expression of FIT (bHLH29), bHLH38, bHLH39, bHLH100, and bHLH101 and promoting the degradation of FIT protein, a key regulator of iron uptake in Arabidopsis. We further demonstrated that the subgroup IVa bHLH proteins, bHLH18, bHLH19, bHLH20, and bHLH25, are novel interactors of FIT, which promote JA-induced FIT protein degradation. These four IVa bHLHs function redundantly to antagonize the activity of the Ib bHLHs (such as bHLH38) in regulating FIT protein stability under iron deficiency. The four IVa bHLH genes are primarily expressed in roots, and are inducible by JA treatment. Moreover, we found that MYC2 and JAR1, two critical components of the JA signaling pathway, play critical roles in mediating JA suppression of the expression of FIT and Ib bHLH genes, whereas they differentially modulate the expression of bHLH18, bHLH19, bHLH20, and bHLH25 to regulate FIT accumulation under iron deficiency. Taken together, these results indicate that by transcriptionally regulating the expression of different sets of bHLH genes JA signaling promotes FIT degradation, resulting in reduced expression of iron-uptake genes, IRT1 and FRO2, and increased sensitivity to iron deficiency. Our data suggest that there is a multilayered inhibition of iron-deficiency response in the presence JA in Arabidopsis.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/physiology , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cyclopentanes/metabolism , Iron/metabolism , Oxylipins/metabolism , Plant Growth Regulators/metabolism , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Biological Transport/genetics , Carrier Proteins/genetics , Cell Nucleus/metabolism , Cyclopentanes/pharmacology , FMN Reductase/genetics , Gene Expression Regulation, Plant/drug effects , Homeostasis , Intracellular Signaling Peptides and Proteins , Iron Deficiencies , Oxylipins/pharmacology , Plant Growth Regulators/pharmacology , Plant Roots/genetics , Plant Roots/growth & development , Plant Roots/metabolism , Plant Roots/physiology , Protein Binding , Protein Stability , Signal TransductionABSTRACT
BACKGROUND AND PURPOSE: Antioxidants provide a promising therapeutic effect for the cardiovascular disease. Luteolin, a polyphenolic bioflavonoid, is known to confer cardioprotection, although the underlying mechanisms, especially the role of luteolin on the antioxidant enzymes, such as the peroxiredoxin family, remain unknown. EXPERIMENTAL APPROACH: We measured the effects of luteolin on myocardial ischaemia/reperfusion (MI/R) injury in vivo (Sprague-Dawley rats) and in vitro, together with the underlying mechanisms, with a focus on signalling by peroxiredoxins. H9c2 cells were used to assess the changes in peroxiredoxins and the other antioxidant enzymes. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also assayed. KEY RESULTS: Luteolin exerted significant cardioprotective effects in vivo and in vitro via improving cardiac function, increasing the expression of anti-apoptotic protein Bcl-2 and decreasing the pro-apoptotic protein Bax and active caspases 3 and 9, associated with MI/R. Mechanistically, luteolin markedly enhanced expression of peroxiredoxin II, without significant effects on other forms of peroxiredoxin, catalase or SOD1. Molecular docking showed that luteolin could indeed bind to the enzymic active pocket of peroxiredoxin II. Furthermore, down-regulation of peroxiredoxin II by peroxiredoxin II-antisense, administered by adenovirus infection of H9c2 cardiomyocytes, and inhibition of peroxiredoxin II in vivo significantly reversed the cardioprotective effects of luteolin. CONCLUSIONS AND IMPLICATIONS: Our findings, for the first time, demonstrate that luteolin protects against MI/R injury through promoting signalling through the endogenous antioxidant enzyme, peroxiredoxin II, indicating the important beneficial role of this antioxidant system in the heart.
Subject(s)
Cardiotonic Agents , Luteolin , Myocardial Reperfusion Injury/drug therapy , Peroxiredoxins/metabolism , Animals , Apoptosis/drug effects , Cardiotonic Agents/pharmacology , Cardiotonic Agents/therapeutic use , Cell Line , Luteolin/pharmacology , Luteolin/therapeutic use , Myocardial Reperfusion Injury/metabolism , Rats, Sprague-DawleyABSTRACT
Fe and Zn are essential micronutrients for plant growth, and the interrelationship regarding their homeostasis is very complicated. In this study, we identified a FIT-binding protein (FBP) using the yeast two-hybrid system. The C-terminus of FBP binds to the bHLH domain of FIT, abolishing the DNA-binding capacity of FIT. Knockout of FBP results in an enhanced expression of NAS genes and a higher nicotianamine content, and the fbp mutant exhibits tolerance to excessive Zn. Physiological analyses reveal that the mutant fbp retains a larger amount of Zn in roots and transfers a greater proportion of Fe to shoots than that in wild type under Zn-excessive stress. As FBP is expressed in the root stele, the negative regulation caused by sequestration of FIT is restricted to this tissue, whereas other FIT-regulated genes, such as IRT1 and FRO2, which mainly expressed in root epidermis, do not show transcriptional upregulation in the fbp mutant. As an antagonistic partner, FBP offers a new approach to spatially fine-tune the expression of genes controlled by FIT. In conclusion, our findings provide a new insight to understand the interrelationship of Fe and Zn homeostasis in plants.
Subject(s)
Arabidopsis Proteins/physiology , Arabidopsis/metabolism , DNA-Binding Proteins/physiology , Homeostasis , Iron/metabolism , Zinc/metabolism , Arabidopsis Proteins/metabolism , Chlorophyll/metabolism , Chromatin Immunoprecipitation , DNA-Binding Proteins/metabolism , Gene Knockdown Techniques , Plant Roots/metabolism , Plant Shoots/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Two-Hybrid System TechniquesABSTRACT
The metabolism of glucose is a nearly exclusive source of energy for maintaining neuronal survival, synaptic transmission and information processing in the brain. Two glucose metabolism pathways have been reported, direct neuronal glucose uptake and the astrocyte-neuron lactate shuttle (ANLS), which can be involved in these functions simultaneously or separately. Although ANLS in the dorsal hippocampus (DH) has been proved to be required for memory consolidation, the specific metabolic pathway involved during memory acquisition remains unclear. The DH and amygdala are two key brain regions for acquisition of contextual fear conditioning (CFC). In 2-NBDG experiments, we observed that 2-NBDG-positive neurons were significantly increased during the acquisition of CFC in the DH. However, in the amygdala and cerebellum, 2-NBDG-positive neurons were not changed during CFC training. Strikingly, microinjection of a glucose transporter (GLUT) inhibitor into the DH decreased freezing values during CFC training and 1 h later, while injection of a monocarboxylate transporter (MCT) inhibitor into the amygdala also reduced freezing values. Therefore, we demonstrated that direct neuronal glucose uptake was the primary means of energy supply in the DH, while ANLS might supply energy in the amygdala during acquisition. Furthermore, knockdown of GLUT3 by a lentivirus in the DH impaired the acquisition of CFC. Taken together, the results indicated that there were two different glucose metabolism pathways in the DH and amygdala during acquisition of contextual fear memory and that direct neuronal glucose uptake in the DH may be regulated by GLUT3.
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PURPOSE: Previous studies have supported an association between serum insulin-like growth factor-1 (IGF1) and IGF-binding protein 3 (IGFBP3) levels and hepatocellular carcinoma (HCC), but the results were inaccurate. It has recently been proposed that IGF1 and IGFBP3 play roles in the time-to-progression (TTP) and overall survival (OS) of HCC patients. Our results revealed that serum IGF1 level is predictive of the progression and survival of HCC patients. RESULTS: HCC was associated with a significant reduction in serum IGF-1 and IGFBP-3 levels compared to cirrhosis (p = 0.037). Low serum IGF1 levels were predictive of a shorter TTP (OR, 2.74; 95% confidence interval [CI], 1.92-3.90) and poorer OS (odds ratio [OR], 2.20; 95% CI, 1.81-2.68) in HCC patients. The IGF1/IGFBP3 molar ratio was not significantly associated with the risk of HCC (OR, 1.311; 95% CI, 0.761-2.260). MATERIALS AND METHODS: We conducted a comprehensive literature search in PubMed, EMBASE, and the Cochrane Library. Twenty studies met the inclusion criteria and were subjected to statistical analysis. The geometric mean and standard deviation (SD) of serum IGF1 and IGFBP3 levels in the healthy, cirrhosis, and HCC groups were calculated. Pooled odds ratios (ORs) were calculated using a fixed-effects model to analyse the association of serum IGF1 level with the progression and survival of HCC patients. CONCLUSIONS: Serum IGF1 and IGFBP3 levels were positively associated with the incidence of HCC. Serum IGF1 level is an independent prognostic factor for the progression and survival of HCC patients.
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Diagnostic ions filter method was used to rapidly detect and identify the phenolic compounds in Rheum palmatum based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). The representative authentic standards of phenolic compounds, including gallic acid, (+)-catechin, (ï¼)-epicatechin, (ï¼)-epicatechin-3-O-gallate and procyanidin B2, were subjected to analysis by UPLC-Q-TOF/MSE system with negative ion mode. Fragmentation patterns of each standard were summarized based on assigned fragment ions. The prominent product ions were selected as diagnostic ions. Subsequently, diagnostic ions filter was employed to rapidly recognize analogous skeletons. Combined with retention time, accurate mass, characteristic fragments and previous literature data, the structures of the filtered compounds were identified or tentatively characterized. A total 63 phenolic compounds (36 phenolic acid derivatives, 8 flavonoid derivatives and 19 tennis derivatives) in R. palmatum were identified, including 6 potential new compounds. The method of diagnostic ions filter could rapidly detect and identify phenolic compounds in R. palmatum This study provides a method for rapid detection of phenolic compounds in R. palmatum and is expected to complete the material basis of rhubarb.
Subject(s)
Phenols/analysis , Phytochemicals/analysis , Rheum/chemistry , Catechin/analysis , Chromatography, High Pressure Liquid , Flavonoids/analysis , Gallic Acid/analysis , IonsABSTRACT
We report the complete genome sequence of Lactobacillus plantarum CGMCC 8198, a novel probiotic strain isolated from fermented herbage. We have determined the complete genome sequence of strain L. plantarum CGMCC 8198, which consists of genes that are likely to be involved in dairy fermentation and that have probiotic qualities.
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Restorations of 98 implant-supported single crowns in anterior maxillary area were divided into 5 groups: zirconia abutment, titanium abutment, and gold/gold hue abutment with zirconia coping, respectively, and titanium abutment with metal coping as well as gold/gold hue abutment with metal coping. A reflectance spectrophotometer was used to evaluate the color difference between the implant crowns and contralateral/neighboring teeth, as well as the color difference between the peri-implant soft tissue and the natural marginal mucosa. The mucosal discoloration score was used for subjective evaluation of the esthetic outcome of soft tissue around implant-supported single crowns in the anterior zone, and the crown color match score was used for subjective evaluation of the esthetic outcome of implant-supported restoration. ANOVA analysis was used to compare the differences among groups and Spearman correlation was used to test the relationships. A gold/gold hue abutment with zirconia coping was the best choice for an esthetic crown and the all-ceramic combination was the best for peri-implant soft tissue. Significant correlation was found between the spectrophotometric color difference of peri-implant soft tissue and mucosal discoloration score, while no significant correlation was found between the total spectrophotometric color difference of implant crown and crown color match score.
Subject(s)
Crowns , Dental Implants, Single-Tooth , Dental Materials/chemistry , Esthetics, Dental , Spectrophotometry/methods , Adult , Color , Female , Gingiva , Humans , Male , Young AdultABSTRACT
The improvement of antibiotic rational use in China was studied by usage analysis of combination antibiotic therapy for type I incisions in 244 hospitals. Five kinds of hospitals, including general hospital, maternity hospital, children's hospital, stomatological hospital and cancer hospital, from 30 provinces were surveyed. A systematic random sampling strategy was employed to select outpatient prescriptions and inpatient cases in 2011 and 2012. A total of 29 280 outpatient prescriptions and 73 200 inpatient cases from 244 hospitals in each year were analyzed. Data were collected with regards to the implementation of the national antibiotic stewardship program (NASP), the overall usage and the prophylactic use of antibiotic for type I incisions. Univariate analysis was used for microbiological diagnosis rate before antimicrobial therapy, prophylactic use of antibiotics for type I incision operation, and so on. For multivariate analysis, the use of antibiotics was dichotomized according to the guidelines, and entered as binary values into logistic regression analysis. The results were compared with the corresponding criteria given by the guidelines of this campaign. The antibiotic stewardship in China was effective in that more than 80% of each kind of hospitals achieved the criteria of recommended antibiotics varieties. Hospital type appeared to be a factor statistically associated with stewardship outcome. The prophylactic use of antibiotics on type I incision operations decreased by 16.22% (P<0.05). The usage of combination antibiotic therapy for type I incisions was also decreased. Region and bed size were the main determinants on surgical prophylaxis for type I incision. This national analysis of hospitals on antibiotic use and stewardship allows relevant comparisons for bench marking. More efforts addressing the root cause of antibiotics abuse would continue to improve the rational use of antibiotics in China.
Subject(s)
Anti-Bacterial Agents/adverse effects , Drug Utilization , Hospitals , Surgical Wound/epidemiology , Anti-Bacterial Agents/therapeutic use , China/epidemiology , Drug Prescriptions , Female , Humans , Inpatients , Male , Outpatients , Surgical Wound/microbiology , Surgical Wound/therapyABSTRACT
OBJECTIVE: To observe the effect of Electroacupuncture (EA) stimulation of "Tianquan"(PC 2), "Quze" (PC 3), "Neiguan" (PC 6), "Daling" (PC 7) of the Pericardium Meridian on cerebral angiogenesis in cerebral ischemia (CI) rats, so as to reveal its mechanisms underlying improvement of stroke. METHODS: A total of 50 SD rats were equally randomized into normal control, sham, model, EA-Pericardium-Meridian acupoints (EA-PCM) and EA-Lung-Meridian acupoint (EA-LUM) groups. The CI model was established by occlusion of the middle cerebral artery. EA (2-4 V, 20 Hz) was applied to PC 2, PC 3, PC 6, PC 7 and "Tianfu"(LU 3), "Chize" (LU 5), "Lieque" (LU 7), "Taiyuan" (LU 9) of the Lung Meridian for 30 min, once at time-points of 0 h, 6 h, 24 h, 48 h and 72 h, respectively after modeling. Serum nerve growth factor (NGF) and Nogo protein-A (Nogo-A) contents were assayed by enzyme linked immunosorbent assay (ELISA), and cerebral NGF and Nogo-A immunoactivity levels in the ischemic cerebral tissue were detected by immunohistochemistry. RESULTS: (1) Compared to the normal control group, serum NGF and Nogo-A contents, and cerebral NGF immunoactivity level in the model group were significantly increased (P < 0.01). Following EA interventions, serum and cerebral NGF levels were further significantly up-regulated in the EA-PCM and EA-LUM groups (P < 0.01), while serum Nogo-A contents were down-regulated in the two EA groups (P < 0.01). The effect of EA-PCM was markedly superior to that of EA-LUM in up-regulating serum and cerebral NGF levels and down-regulating serum No- go-A level (P < 0.01). No significant differences were found between the normal control and sham groups in serum and cerebral NGF and Nogo-A levels (P > 0.05) , and among the 5 groups in cerebral Nogo-A levels (P > 0.05). CONCLUSION: EA stimulation of acupoints of both Pericardium Meridian and Lung Meridian can up-regulate serum NGF, cerebral NGF expression and down-regulate serum Nogo-A in CI rats, and the effect of Pericardium Meridian is markedly superior to that of Lung Meridian, suggesting a possible better nerve repair effect of EA-PCM acupoints on ischemic brain.
Subject(s)
Acupuncture Points , Brain Ischemia/therapy , Electroacupuncture , Myelin Proteins/blood , Nerve Growth Factor/blood , Animals , Brain Ischemia/blood , Brain Ischemia/genetics , Humans , Male , Meridians , Myelin Proteins/genetics , Nerve Growth Factor/genetics , Nogo Proteins , Rats , Rats, Sprague-DawleyABSTRACT
The Wnt signaling pathway plays critical roles in development. However, to date, the role of Wnts in learning and memory in adults is still not well understood. Here, we aimed to investigate the roles and mechanisms of Wnts in hippocampal-dependent contextual fear conditioning (CFC) memory formation in adult mice. CFC training induced the secretion and expression of Wnt3a and the activation of its downstream Wnt/Ca(2+) and Wnt/ß-catenin signaling pathways in the dorsal hippocampus (DH). Intrahippocampal infusion of Wnt3a antibody impaired CFC acquisition and consolidation, but not expression. Using the Wnt antagonist sFRP1 or the canonical Wnt inhibitor Dkk1, we found that Wnt/Ca(2+) and Wnt/ß-catenin signaling pathways were involved in acquisition and consolidation, respectively. Moreover, we found Wnt3a signaling is not only necessary but also sufficient for CFC memory. Intrahippocampal infusion of exogenous Wnt3a could enhance acquisition and consolidation of CFC. Overexpression of constitutively active ß-catenin in the DH could rescue the deficit in CFC memory consolidation, but not acquisition induced by Wnt3a antibody injection, which suggests ß-catenin signaling pathway acts downstream of Wnt3a to mediate CFC memory consolidation. Our study may help further the understanding of the precise regulation of Wnt3a in differential memory phases depending on divergent signaling pathways.
Subject(s)
Conditioning, Psychological/physiology , Fear/psychology , Hippocampus/metabolism , Memory/physiology , Wnt Signaling Pathway/physiology , Wnt3 Protein/metabolism , Analysis of Variance , Animals , Antibodies/pharmacology , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Conditioning, Psychological/drug effects , Fear/drug effects , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Hippocampus/drug effects , Intercellular Signaling Peptides and Proteins/pharmacology , Male , Memory/drug effects , Mice , Mice, Inbred C57BL , RNA, Messenger/metabolism , Transduction, Genetic , Wnt Signaling Pathway/drug effects , Wnt3 Protein/genetics , Wnt3 Protein/immunology , beta CateninABSTRACT
Stabilization of oil/oil Pickering emulsions using robust and recyclable catalytic amphiphilic silica nanoparticles bearing alkyl and propylsulfonic acid groups allows fast and efficient solvent-free acetalization of immiscible long-chain fatty aldehydes with ethylene glycol.