ABSTRACT
With the development of green buildings, people pay more attention to the quality of the indoor sound environment. The air sound insulation performance of floors and exterior walls plays a key role in today's green buildings. The thermal performance of the enclosure structure's floor and exterior wall heat transfer resistance is an important factor in reducing building carbon emissions in green buildings. The aim of this paper is to study the efficiency of the acoustic and thermal insulation of a foaming system with porous carbon balls and the combination of different structural ways of construction boards and external walls. The acoustic and thermal parameters of different sound insulation and thermal insulation systems designed with porous carbon sphere foam and inserted into the floors and exterior walls are compared to highlight the optimal structure. The theoretical and experimental tests showed that to improve the sound insulation performance of the floor, a sound insulation system needs to be placed on the surface of the floor in contact with the impact object and inlaid in the vertical gap in contact with the floor and the wall. Furthermore, it has been determined that the surface of the foam particle acoustic ball with micropores has good sound absorption performance. Finally, the high-quality building thermal insulation material with low thermal conductivity in any combination with the floor slabs and the external wall structure improves the thermal insulation performance.
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Anterior uveitis (AU) is an immune-mediated inflammatory disease that results in iritis, cyclitis, glaucoma, cataracts, and even a loss of vision. The frequent and long-term administration of corticosteroid drugs is limited in the clinic owing to the side effects and patient noncompliance with the drugs. Therefore, specifically delivering drugs to inflammatory anterior segment tissues and reducing the topical application dosage of the drug are still a challenge. Here, we developed dual dexamethasone (Dex) and curcumin (Cur)-loaded reactive oxygen species (ROS)-responsive nanoparticles (CPDC NPs) to treat anterior uveitis. The CPDC NPs demonstrated both anti-inflammatory and antioxidative effects, owing to their therapeutic characteristics of dexamethasone and curcumin, respectively. The CPDC NPs could effectively release dexamethasone and curcumin in the oxidizing physiological environment of the inflammation tissue. The CPDC NPs can effectively internalize by activated macrophage cells, subsequently suppressing the proinflammatory factor expression. Moreover, the CPDC NPs can inhibit ROS and inflammation via nuclear transcription factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway activation. In an endotoxin-induced uveitis rabbit model, the CPDC NPs show a therapeutic effect that is better than that of either free drugs or commercial eye drops. Importantly, the CPDC NPs with a lower dexamethasone dosage could reduce the side effects significantly. Taken together, we believe that the dual-drug-loaded ROS-responsive NPs could effectively target and inhibit inflammation and have the potential for anterior uveitis treatment in clinical practice.
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AIM To explore the effect of Compound Fo'ercao Mixture on TLR4/MyD88/NF-κB signaling pathway in a rat model of chronic obstructive pulmonary disease(COPD).METHODS Rats were randomly divided into the blank group(n=10),and the model group(n=50)for the establishment of a rat model of COPD by 12-week cigarette smoke exposure combined with intratracheal injection of LPS.The successful rat models were randomly divided into the model group,the dexamethasone group(0.5 mg/kg)and the low,medium and high dose Compound Fo'ercao Mixture groups(6.8,13.6 and 27.2 g/kg),with 10 rats in each group.After 24 weeks of drug intervention,the rats had their lung function detected by animal lung function meter;their pathological changes of lung tissue observed by HE staining;their serum TNF-α,IL-1β,IL-6,and MDA levels and SOD activity detected by ELISA;their pulmonary mRNA expressions of TLR4,MyD88,NF-κB and caspase-3 detected by RT-qPCR;and their pulmonary protein expressions of TLR4,MyD88,NF-κB and TNF-α detected by Western blot.RESULTS Compared with the blank group,the model group displayed obviously pulmonary ventilation dysfunction,damaged lung tissue and bronchus,decreased SOD activity(P<0.01);increased serum TNF-α,IL-1β,IL-6 and MDA levels(P<0.01);and increased pulmonary expressions of TLR4,MyD88,NF-κB and caspase-3 mRNA and TLR4,MyD88,NF-κB and TNF-α proteins(P<0.01).Compared with the model group,all Compound Fo'ercao Mixture groups shared improvement in lung function indices levels and lung tissue damage;decrease in the levels of serum TNF-α,IL-1β,IL-6 and MDA(P<0.05,P<0.01);and decrease in the pulmonary expressions of TLR4,MyD88,NF-κB and caspase-3 mRNA and TLR4,MyD88,NF-κB and TNF-α protein(P<0.05,P<0.01)in a dose-dependent manner.CONCLUSION Compound Fo'ercao Mixture can improve the lung dysfunction and pathological injury in a rat model of COPD,and its mechanism may be associated with the regulated TLR4/MyD88/NF-κB signaling pathway.
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Acute methicillin resistant Staphylococcus aureus (MRSA) pneumonia is one of the most frequently seen lung infection diseases with high morbidity and mortality. It is urgent to explore an efficient antibacterial strategy owing to the increase of drug resistance, virulence, and pathogenicity of MRSA. It was found that Fe3O4 can induce ferroptosis in MRSA, but its effect was inhibited by glutathione (GSH) to a certain extent, while cinnamaldehyde (CA) can enhance ferroptosis by consuming GSH. As a bacterial quorum sensing (QS) inhibitor, CA can suppress the QS system and further exert its antibacterial and antibiofilm effects. Here, we developed an Fe3O4-based ferroptosis inducer to promote ferroptosis in MRSA, interrupt the QS, destroy biofilm, and thus effectively treat acute MRSA pneumonia. We used sodium alginate (SA) to wrap Fe3O4 and CA to form particles, and then coated the surface with a hybrid biomimetic membrane composed of an erythrocyte membrane and platelet membrane to obtain lung targeted antibacterial particles (mFe-CA). Under ultrasonic (US) stimulation, mFe-CA can efficiently release Fe3O4 and CA, thereby synergically inducing MRSA death with the characteristics of ferroptosis, including mass ROS production, lipid peroxidation, GSH depletion, and respiratory chain suppression. Furthermore, mFe-CA + US can inhibit the QS system, remove biofilms, and reduce strain virulence. In the mouse model of MRSA pneumonia, mFe-CA + US treatment markedly advanced the survival rate of the mice, reduced the bacterial load in the lungs, and alleviated the inflammatory damage, but there was no obvious toxicity. This study proposes an antibacterial substitute to induce ferroptosis of MRSA, which may provide a foreground for overcoming microbial drug resistance and fighting biofilm-associated infections and also provides a target and theoretical basis for clinical treatment of acute MRSA pneumonia.
Subject(s)
Ferroptosis , Methicillin-Resistant Staphylococcus aureus , Pneumonia , Animals , Mice , Biomimetics , Anti-Bacterial Agents/pharmacology , Biofilms , Microbial Sensitivity TestsABSTRACT
Freehand 3-D ultrasound systems have been advanced in scoliosis assessment to avoid radiation hazards, especially for teenagers. This novel 3-D imaging method also makes it possible to evaluate the spine curvature automatically from the corresponding 3-D projection images. However, most approaches neglect the three-dimensional spine deformity by only using the rendering images, thus limiting their usage in clinical applications. In this study, we proposed a structure-aware localization model to directly identify the spinous processes for automatic 3-D spine curve measurement using the images acquired with freehand 3-D ultrasound imaging. The pivot is to leverage a novel reinforcement learning (RL) framework to localize the landmarks, which adopts a multi-scale agent to boost structure representation with positional information. We also introduced a structure similarity prediction mechanism to perceive the targets with apparent spinous process structures. Finally, a two-fold filtering strategy was proposed to screen the detected spinous processes landmarks iteratively, followed by a three-dimensional spine curve fitting for the spine curvature assessments. We evaluated the proposed model on 3-D ultrasound images among subjects with different scoliotic angles. The results showed that the mean localization accuracy of the proposed landmark localization algorithm was 5.95 pixels. Also, the curvature angles on the coronal plane obtained by the new method had a high linear correlation with those by manual measurement (R = 0.86, p < 0.001). These results demonstrated the potential of our proposed method for facilitating the 3-D assessment of scoliosis, especially for 3-D spine deformity assessment.
Subject(s)
Scoliosis , Adolescent , Humans , Scoliosis/diagnostic imaging , Vertebral Body , Spine/diagnostic imaging , Imaging, Three-Dimensional/methods , Ultrasonography/methodsABSTRACT
Tracking the myotendinous junction (MTJ) motion in consecutive ultrasound images is essential to assess muscle and tendon interaction and understand the mechanics' muscle-tendon unit and its pathological conditions during motion. However, the inherent speckle noises and ambiguous boundaries deter the reliable identification of MTJ, thus restricting their usage in human motion analysis. This study advances a fully automatic displacement measurement method for MTJ using prior shape knowledge on the Y-shape MTJ, precluding the influence of irregular and complicated hyperechoic structures in muscular ultrasound images. Our proposed method first adopts the junction candidate points using a combined measure of Hessian matrix and phase congruency, followed by a hierarchical clustering technique to refine the candidates approximating the position of the MTJ. Then, based on the prior knowledge of Y-shape MTJ, we finally identify the best matching junction points according to intensity distributions and directions of their branches using multiscale Gaussian templates and a Kalman filter. We evaluated our proposed method using the ultrasound scans of the gastrocnemius from 8 young, healthy volunteers. Our results present more consistent with the manual method in the MTJ tracking method than existing optical flow tracking methods, suggesting its potential in facilitating muscle and tendon function examinations with in vivo ultrasound imaging.
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AIM To optimize the TLC identification method for Cirsii Herba and to study the changes in quality properties"carbonizing retains characteristics"of Cirsii Herba Carbonisata.METHODS After the improvement of thin layer plate and solvent in the TLC identification based on the Chinese Pharmacopoeia 2020 Edition for Cirsii Herba,Cirsii Herba Carbonisata had its TLC identification method and UPLC fingerprint established for the determination of its content of buddleoside and acacetin as well.RESULTS We used silica gel G plate,and the solvent of toluene-acetone-formic acid-methanol(6 ∶ 3 ∶ 0.5 ∶ 2.5)for TLC identification of Cirsii Herba.The content variations of buddleoside and acacetin in Cirsii Herba and its differently charred products were consistent with the result of the TLC identification.CONCLUSION The improved TLC identification method for Cirsii Herba is of lower cost and less solvent toxicity compared to the method in the Chinese Pharmacopoeia 2020 Edition,and can identify the changes in quality properties"carbonizing retains characteristics"of differently charred Cirsii Herba,therefore it can be used to control the quality of Cirsii Herba Carbonisata in the market.
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Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.
Subject(s)
Gene Expression Profiling , Phylogeny , Artemisia/genetics , Basic-Leucine Zipper Transcription Factors/metabolism , Terpenes , Gene Expression Regulation, PlantABSTRACT
Aim To study the effect of sodium pyruvate on apoptosis and autophagy of HT22 in mouse hippocampal neuronal cells under hypoxia conditions. Methods HT22 cells were incubated with different concentrations of sodium pyruvate to detect their cellular activity by MTS; iron staining was used to further observe the effect of sodium pyruvate on HT22 cells in mitochondrial metabolism; lysosomal staining was applied to detect the lysosomal changes of sodium pyruvate on HT22 cells; Western blot was used to detect the expression of Bcl-2, Bax and LC3-II/LC3- I proteins. Results To verify whether sodium pyruvate exerted neuroprotective effects on mouse hippocampal HT22 cells through affecting mitochondrial apoptosis and autophagy pathways, which were improved by administration of sodium pyruvate. Conclusions Sodium pyruvate administration under hypoxic conditions can reduce the neuroprotective effect of hypoxic injury by reducing apoptosis and activating autophagy in HT22 cells.
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OBJECTIVES@#To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*METHODS@#The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.@*RESULTS@#The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively.@*CONCLUSIONS@#This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.
Subject(s)
Chromatography, Liquid/methods , Tandem Mass Spectrometry , Methanol , Carbamazepine/analysis , Benzodiazepines/analysis , Solvents , Chromatography, High Pressure Liquid , Solid Phase ExtractionABSTRACT
Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.
Subject(s)
Humans , Male , Consanguinity , Pakistan , Infertility, Male/metabolism , Semen/metabolism , Sperm Tail/metabolism , Spermatozoa/metabolism , Flagella/pathology , MutationABSTRACT
OBJECTIVES@#To study the effect of procalcitonin (PCT) on lipopolysaccharide (LPS)-induced expression of the pyroptosis-related proteins nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and caspase-1 in human umbilical vein endothelial cells (HUVECs).@*METHODS@#HUVECs were induced by LPS to establish a model of sepsis-induced inflammatory endothelial cell injury. The experiment was divided into two parts. In the first part, HUVECs were randomly divided into four groups: normal control, LPS (1 μg/mL), PCT (10 ng/mL), and LPS+PCT (n=3 each). In the second part, HUVECs were randomly grouped: normal control, LPS, and LPS+PCT of different concentrations (0.1, 1, 10, and 100 ng/mL) (n=3 each). Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of NLRP3 and caspase-1 in each group.@*RESULTS@#In the first experiment: compared with the normal control group, the PCT, LPS, and LPS+PCT groups had significantly upregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05); compared with the LPS group, the LPS+PCT group had significantly downregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05). In the second experiment: compared with those in the LPS group, the mRNA and protein expression levels of NLRP3 and caspase-1 in the LPS+PCT of different concentrations groups were significantly downregulated in a concentration-dependent manner (P<0.05).@*CONCLUSIONS@#LPS can promote the expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs, while PCT can inhibit the LPS-induced expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs in a concentration-dependent manner.
Subject(s)
Humans , Caspase 1/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Lipopolysaccharides/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Procalcitonin , Nucleotides/pharmacologyABSTRACT
Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.
Subject(s)
Humans , Non-alcoholic Fatty Liver Disease/metabolism , Liver , Medicine, Chinese Traditional/adverse effects , Receptors, Cytoplasmic and Nuclear/metabolismABSTRACT
OBJECTIVE@#To explore clinical effect of arthroscopy-assisted rotator cuff tendon transfer in treating irreparable rotator cuff tears (IRCT).@*METHODS@#From May 2015 to May 2018, 23 patients with unrepairable rotator cuff tears were treated with arthroscopy-assisted rotator cuff tendon transfer, and 21 patients were followed up finally, including 8 males and 13 females, aged from 48 to 82 years old with an average of(64.3±9.1) years old;the courses of disease ranged from 6 to 36 months with an average of (14.0±6.4) months. American Rotator and Elbow Surgeons Score(ASES) and Constant-Murley score were used to evaluate clinical efficacy before surgery and at the latest follow-up.@*RESULTS@#All 21 patients were followed up for 36 to 54 months with an average of (39.4±4.4) months. Axillary incision of 1 patient was redness, swelling and exudation after surgery, which healed after 3 weeks of dressing change, and exudate culture was negative. At the latest follow-up, MRI showed partial tearing of the metastatic tendon in 2 patients, but pain and movement of the affected shoulder were still better than before surgery. ASES increased from preoperative (41.0±9.6) scores to the latest follow-up (75.6±14.0) scores, and had statistical difference (t=10.50, P<0.01). Constant-Murley score increased from (49.8±7.1) scores before operation to (67.5±11.6) scores at the latest follow-up (t=11.27, P<0.01).@*CONCLUSION@#Arthroscopic assisted latissimus dorsalis tendon transposition restores physiological and anatomical structure of glenohumeral joint by reconstructing balance of horizontal and vertical couples of shoulder joint, thus achieving the stability of the shoulder joint, relieving shoulder pain and improving shoulder joint function.
Subject(s)
Male , Female , Humans , Middle Aged , Aged , Aged, 80 and over , Rotator Cuff Injuries/surgery , Superficial Back Muscles , Rotator Cuff , Treatment Outcome , Shoulder Joint/surgery , Tendon Transfer , Arthroscopy , Range of Motion, Articular/physiologyABSTRACT
BACKGROUND: This study aimed to evaluate the clinical efficacy of Chinese medicine for the treatment of centrally mediated abdominal pain syndrome (CAPS) using a meta-analysis system. METHODS: Six databases, including China National Knowledge Infrastructure, Vendor Information Pages, Chinese Biomedical Database, Wanfang, PubMed, and Embase were searched for randomized controlled trials related to the treatment of CAPS with traditional Chinese medicine. The bias risk assessment tool and RevMan5.3 software (Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration) were used to conduct quality assessment and meta-analysis, and the GRADE grading system was used to evaluate the quality of evidence for outcome indicators. RESULTS: Fifteen articles were included in this study. Meta-analysis results showed that the treatment group was more effective in terms of the total effective rate (relative riskâ =â 1.27; 95% confidence interval [CI], 1.19-1.34; Pâ <â .00001), Behavioral Rating Scale-6 pain score (mean difference [MD] = -0.79; 95% CI, -0.99 to -0.59; Pâ <â .00001), and traditional Chinese medicine (TCM) symptom score (MD = -1.74; 95% CI, -2.23 to -1.26; Pâ <â .00001) than the control group (Pâ <â .05). However, in terms of numerical rating scale pain score (MDâ =â 0.79; 95% CI, -1.70 to 0.12; Pâ =â .09), the efficacy was comparable between the 2 groups, and the difference was not statistically significant (Pâ >â .05). In terms of verbal rating scale pain, depression, and anxiety scores, the data could not be combined due to inconsistent scoring criteria, and only descriptive analysis was performed. The results showed that the treatment group was slightly better than the control group in terms of relieving verbal rating scale pain and improving anxiety and depression (Pâ <â .05). CONCLUSION: Chinese medicine can effectively improve the pain and TCM clinical symptoms of patients with CAPS and relieve patients' anxiety and depression with fewer adverse effects, which has certain therapeutic advantages. However, because of the low methodological quality assessment of the included literature, the quality of GRADE evidence for outcome indicators is of mostly low and very low quality, the strength of recommendation is weak, and the credibility of the conclusion is average. More rigorous, larger sample, and higher-quality clinical trials are required to provide a higher level of evidence-based medicine for the development of TCM treatment standards for CAPS.
Subject(s)
Medicine, Chinese Traditional , Publications , Abdominal Pain/drug therapy , Humans , Syndrome , Treatment OutcomeABSTRACT
Based on the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology, the components of Daqinglong Decoction absorbed in serum were analyzed and identified, and the therapeutic material basis of the prescription was revealed via network pharmacology. UPLC conditions are as follows: Waters Acquity UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm), mobile phase of 0.1% formic acid aqueous solution(A)-0.1% formic acid in acetonitrile(B), gradient elution. Peakview 2.0 and MetabolitePilot 1.5 were employed for the comparison of Daqinglong Decoction, blank serum, and serum after the administration of the decoction, and the components of Daqinglong Decoction absorbed in serum were analyzed based on MS/MS profiles in related database and literature. The targets of the components absorbed in serum were retrieved from SwissTargetPrediction, DrugBank, and Batman-TCM. With the search terms of common cold, influenza, flu, bronchitis, bronchiolitis, asthma, allergic rhinitis, rhinallergosis, allergic coryza, rheumatic arthritis, and nephritis, the related disease targets were screened out. Then the absorbed component-potential target gene network and absorbed component target-disease target network were constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the core targets. iGEMDOCK was employed for molecular docking of the absorbed components and core targets. In the serum after the administration of the decoction, 28 components were preliminarily identified, with 21 prototypes and 7 metabolites. Among them, 5 core components of ephedrine, demethylephedrine, glycyrrhetinic acid, p-hydroxybenzoic acid, and 2-methoxybenzoic acid were screened out, and 9 core targets, such as JUN, tumor protein 53(TP53), and protein kinase B(AKT1), were identified. Molecular docking showed high binding affinity of core components and core targets. Therefore, Daqinglong Decoction may exert therapeutic effect by regulating mitogen-activated protein kinase(MAPK), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG) signaling pathways and further improving and regulating inflammatory response and other physiological and pathological processes. This study clarifies the components of Daqinglong Decoction absorbed in serum and explores the therapeutic material basis of the prescription, which provides a reference for further elucidating the mechanism of Daqinglong Decoction and its clinical application.
Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacology , Molecular Docking Simulation , Network PharmacologyABSTRACT
Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
Subject(s)
Humans , Male , Asthenozoospermia/pathology , Dyneins/genetics , Homozygote , Microtubule-Associated Proteins , Mutation , Mutation, Missense , Sperm Tail/metabolismABSTRACT
Objective: To evaluate the safety and feasibility of laparoscopic surgery after neoadjuvant chemotherapy for pancreatic cancer. Methods: Clinical data of 8 patients underwent laparoscopic surgery after neoadjuvant chemotherapy for pancreatic cancer at Fudan University Shanghai Cancer Center from September 2019 to June 2020 were reviewed retrospectively. There were 5 males and 3 females,aged from 47 to 72 years old. All patients underwent abdominal enhanced CT and PET-CT before operation to accurately evaluate the tumor stage and exclude distant metastasis. Results: Neoadjuvant chemotherapy with AG regimen(gemcitabine 1 000 mg/m2 and albumin bound paclitaxel 125 mg/m2) was received for 2 to 6 cycles before surgery. All 8 patients successfully completed the operation,including 5 cases of pancreaticoduodenectomy,2 cases of radical antegrade modular pancreatosplenectomy(RAMPS),and 1 case of total pancreatectomy. No conversion to laparotomy or laparoscopic assisted surgery. The operation time was 240 to 450 minutes,the blood loss was 100 to 500 ml,the postoperative length of stay was 10 to 16 days. During the follow-up period up to December 31, 2020, there was 1 case suffered grade B pancreatic leakage and abdominal infection. The numbers of resected lymph nodes were 9 to 31. All patients received R0 resection. The follow-up times were 4.5 to 9.5 months. One patient underwent RAMPS was diagnosed as liver metastasis after 2 months of the operation,and the other 7 patients still survived without tumor recurrence. Conclusion: Minimally invasive surgery of pancreatic cancer after neoadjuvant chemotherapy is safe and feasible in experienced pancreatic minimally invasive centers.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , China , Laparoscopy , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Pancreatectomy , Pancreatic Neoplasms/surgery , Positron Emission Tomography Computed Tomography , Retrospective StudiesABSTRACT
Objectives: To study the design of nonmetallic crowns for deciduous molars by means of computer aided design and to analyze the key parameters of the nonmetallic crowns of deciduous molars using finite element method. Methods: The three-dimensional model of a mandibular second primary molar was constructed by using a micro-CT system. The thickness of the crown was limited to 0.5 mm and four different crown shapes (chamfer+anatomic, chamfer+non-anatomic, knife edge+anatomic and knife edge+non-anatomic) were designed. Then, the crown shape was limited as chamfer+non-anatomic and five different thicknesses of the crown (0.50, 0.75, 1.00, 1.25, 1.50 mm) were designed, and three different materials, including polyetherketoneketone (PEKK), polymethylmethacrylate (PMMA) resin and resin-infiltrated ceramic, were applied to make the crown. Stress distribution and fatigue of each component of the model under vertical and oblique loadings were analyzed by using finite element method. Non-axial retention analysis was performed on chamfer+non-anatomic crowns, made of PMMA resin, with thicknesses of 0.50, 0.75, 1.00, 1.25 and 1.50 mm. Results: Among the four crown shape designs, the chamfer+non-anatomic type crown showed the lowest von Mises stress and the highest safety factor. By comparing three different materials, the resin-infiltrated ceramic group showed obvious stress concentration on the buccal edge of the crown and the PEKK group showed stress concentration in the adhesive layer. Results of non-axial retention analysis showed that the torques required by the crowns with five thicknesses at the same rotation angle were as follows: 4 856.1, 4 038.1, 3 497.3, 3 256.3 and 3 074.3 N⋅m, respectively. The comparison of areas of the adhesives fracture among groups were as follows: 0.5 mm group < 0.75 mm group < 1.00 mm group < 1.25 mm group < 1.50 mm group. Conclusions: In the design of nonmetallic crowns for primary molars, the edge of the crown should be designed as chamfer, the shape of the inner crown should be non-anatomical and the minimum preparation amount of the occlusal surface should be 1.00 mm. Among the three materials, PMMA resin, of which elastic modulus is similar to the dentin and the dental adhesive, might be the most suitable material for the crowns of primary molars.