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ObjectiveTo discuss the diagnostic methods of global developmental delay caused by 10q24.3 heterozygous loss. MethodsA retrospective analysis was conducted on the clinical data of one child with global developmental delay， and the results of low depth whole-genome copy number variation sequencing （CNVseq） and family whole exome sequencing （WES） of the child and his parents. ResultsThe patient was a 10-month-old male with developmental retardation in four areas， with some special features （ocular hypertelorism， strabismus， flat nose bridge， protruding forehead， cleft palate， high palatal arch， etc.） and hypotonia of limbs. The CNVseq and WES test showed that the patient had new 10q24.3 heterozygosis loss. Because this region contains the gene SUFU associated with basal cell nevus syndrome and the gene CNNM2 associated with hypomagnesemia， seizures， and mental retardation， and the gene TRIM8 associated of Focal segmental glomerulosclerosis with neurodevelopmental syndrome， we speculated that the cause of the disease in the child was highly related to the heterozygosity deletion of SUFU gene and CNNM2 gene and TRIM8 gene. ConclusionGenetic testing should be improved as soon as possible for children with global developmental delay and special facial manifestations， so as to make clear diagnosis and to judge prognosis.
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ObjectiveTo discuss the correlation between young patients’ adverse transfusion reaction and pre-transfusion C reactive protein （CRP） level and EO% （percentage of eosinophils） . MethodsThe observation group was chosen from among sixty-six young patients who experienced transfusion-related adverse events between January 2019 and December 2020. For each patient chosen to be included in the observation group， another patient from the same department， with the same disease and gender， who had been hospitalized in the same month and received the same type of blood product transfusion， but had not experienced any transfusion-related adverse effects， was chosen to be in the control group. We examined and compared their ages， transfusion experiences， allergy backgrounds， EO%， and CRP levels in peripheral blood prior to transfusion. A receiver operating characteristic （ROC） curve was used to examine the diagnostic value of EO% and CRP for transfusion-related adverse events. Simultaneously， a logistic analysis was performed on the risk factors for transfusion-related adverse events. ResultsPre-transfusion CRP was higher in patients with FNHTR in the observation group than it was in patients in the control group； pre-transfusion CRP was also higher in patients with ATR in the observation group than it was in patients in the control group. There were also statistically significant differences between these variables in the percentage of patients with transfusion history and pre-transfusion EO% （ P＜0.05）. For the transfusion of different blood types， there was statistical significance in the occurrence of ATR and FNHTR （ P＜0.05）. For the diagnosis of FNHTR， the CRP area under the ROC curve was 0.889， and the best cut-off value was 18.05 mg/L. For the diagnosis of ATR， the area under the ROC curve was 0.749， and the best cut-off values were 17.60 mg/L. ConclusionPre-transfusion C-reactive protein level is an independent risk factor for FNHTR and ATR in young patients； the predictive value of EO% for adverse blood transfusion reactions is insufficient.
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OBJECTIVE To systematically evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） in the treatment of metastatic colorectal cancer （mCRC）， so as to provide evidence-based reference for clinical practice. METHODS PubMed， the Cochrane Library， Web of Science， Embase， CNKI， Wanfang and VIP databases were searched to collect randomized controlled trials （RCT） of ICIs （trial group） versus traditional chemotherapy or optimal supportive treatment （control group） in the treatment of mCRC from the establishment of the database to June 1， 2022. After literature screening and data extraction， Cochrane Systematic Review Manual 5.1.0 was used to evaluate the quality of the included literature， and RevMan 5.4 software was used for meta-analysis and sensitivity analysis. RESULTS A total of 4 RCTs were included， involving 833 patients. Meta-analysis showed that the overall survival （OS） [HR＝0.77， 95%CI （0.64， 0.94）， P＝0.01] and progression-free survival （PFS） [HR＝0.67， 95%CI （0.57， 0.79）， P＜0.000 01] were significantly higher in trial group than control group； the difference was not statistically significant when comparing the incidence of grade 3 and above adverse events in the two groups [RR＝1.22， 95%CI （0.77， 1.94）， P＝0.39]. Subgroup analysis by mutation pattern showed that patients with mismatch repair proficiency and low levels of microsatellite instability （pMMR-MSS） mCRC patients in trial group had significantly higher PFS than control group （P＜0.05）. The results of sensitivity analysis showed that the results were robust. CONCLUSIONS Compared with traditional chemotherapy or optimal supportive treatment， ICIs can prolong the OS and PFS of mCRC patients， and maybe has more advantages in pMMR-MSS mCRC patients； the safety of ICIs is equivalent to that of traditional chemotherapy or optimal supportive treatment.
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ObjectiveTo summarize the echocardiographic features of sinus of Valsalva aneurysm （SVA）， analyze the causes of missed diagnosis， thus explore the diagnostic skills and improve the diagnostic accuracy for SVA. MethodsThe echocardiographic features and clinical data of 52 SVA patients who underwent surgery in the First Affiliated Hospital of Sun Yat-sen University from January 2014 to March 2022 were retrospectively reviewed. The patients were divided into 5 types according to modified Sakakibara classification system. ResultsThere were 32 male and 20 female patients with their age of 18~66 （36.1±11.6） years. Of the 52 aneurysms， 44 originated from the right coronary sinus （RCS）， 8 from noncoronary sinus （NCS） and none from left coronary sinus （LCS）. Among the 35 SVAs protruding into the right ventricle， including type I， type Ⅱ and type Ⅲv， 32 （91.4%） were associated with ventricular septal defect （VSD）. There were 2 （17.6%） associated with VSD among the 17 SVAs protruding into the right atrium or other sites of the heart， including type Ⅲa， type Ⅳ and type Ⅴ. SVA was frequently associated with aortic valve disease， 27 cases （51.9%） of which needed surgical valve replacement or valvoplasty. SVA was missed in 4 patients and VSD in 8， with the misdiagnosis rates of 7.7% and 23.5%， respectively. The most commonly missed VSD diagnosis was subarterial VSD with type I SVA. Of the 19 SVAs associated with infective endocarditis （IE）， 2 were missed， with the misdiagnosis rate of 10.5%. ConclusionThe ultrasound images of SVA are diverse and complex. SVA protruding into the right atrium is rarely associated with VSD， while SVA protruding into the right ventricle is frequently associated with VSD. SVA is also prone to be associated with aortic valve disease and IE， which makes the diagnosis more challenging. Therefore， during ultrasound examination， we must vigilantly and flexibly make use of the multiple scan slices so as to decrease the rate of missed diagnosis and improve the diagnostic accuracy for SVA.
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Objective:To explore the role of blended learning in the undergraduate teaching of Clinical Biochemistry. Methods:The Batch 2017 medical laboratory technology undergraduates ( n=134) were selected as research objects, and the effect and opinions of blended learning were statistically analyzed by questionnaire survey and online-offline platform data. SPSS 23.0 was used to conduct rank sum test. Results:The application of blended learning in the Clinical Biochemistry teaching affected the learning effect in an all-round way. The average score increased from 70 (64, 76) to 79 (71, 85), with statistical difference ( Z=6.69, P<0.001). Conclusion:The combined application of blended learning, problem-based learning, flipped classroom and formative assessment is conducive to teaching students in accordance with their aptitude and cultivating students' clinical thinking ability.
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Stroke in the elderly has a high incidence rate and great harm. Strengthening the management of high-risk populations is the key to primary stroke prevention. Disease self-management has a better cost-effectiveness ratio. This article reviews the self-management of the elderly at high risk of stroke from the aspects of current situation, content and influencing factors of self-management.
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Tic disorders(TD)are a group of childhood-onset neuropsychiatric conditions.Due to sudden, aimless, rapid muscle contraction, patients with TD often have different forms of tic such as blinking, frown, shoulder shaking and voice clearing, which seriously affect their quality of life.However, the etiology of TD has not yet been clear, hence the aim of patients management is targeted to symptom relief until now.In fact, many studies have found that the pathogenesis of TD could be a combined effect of multiple factors, including genetic, immunological, psychological and environmental variables.Here, we reviews the results of recent studies on the etiology of TD, hoping to provide new ideas and directions for the etiological research on TD.
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Objective: To explore the effect of down-regulation of retinol binding protein 2 (RBP2) expression on the biological characteristics of ovarian cancer cells and its mechanism. Methods: Knockdown of RBP2 and cisplatin (DDP)-resistant ovarian cancer cell line SKOV3/DDP-RBP2i was established, the negative control group and blank control group were also set. Cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, flow cytometry was used to detect cell apoptosis, scratch test and Transwell invasion test were used to detect cell migration and invasion ability, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expressions of molecular markers related to epithelial-mesenchymal transition (EMT). The effect of RBP2 on the growth of ovarian cancer was verified through experiment of transplanted tumors in nude mice, and the relationships between RBP2 expression and tumor metastasis and patient prognosis were analyzed using the clinical data of ovarian cancer in TCGA database. Results: After down-regulating the expression of RBP2, the proliferation ability of SKOV3/DDP cell was significantly reduced. On the fifth day, the proliferation activities of SKOV3/DDP-RBP2i group, negative control group and blank control group were (56.67±4.16)%, (84.67±3.51) and (87.00±4.00)% respectively, with statistically significant difference (P<0.001). The apoptosis rate of SKOV3/DDP-RBP2i group was (14.19±1.50)%, higher than (8.77±0.75)% of the negative control group and (7.48±0.52)% of the blank control group (P<0.001). The number of invasive cells of SKOV3/DDP-RBP2i group was (55.20±2.39), lower than (82.60±5.18) and (80.80±7.26) of the negative control group and the blank control group, respectively (P<0.001). The scratch healing rate of SKOV3/DDP-RBP2i group was (28.47±2.72)%, lower than (50.58±4.06)% and (48.92±4.63)% of the negative control group and the blank control group, respectively (P<0.001). The mRNA and protein expressions of E-cadherin in the SKOV3/DDP-RBP2i group were higher than those in the negative control group (P=0.015, P<0.001) and the blank control group (P=0.006, P<0.001). The mRNA and protein expression of N-cadherin in SKOV3/DDP-RBP2i group were lower than those in the negative control group (P=0.012, P<0.001) and the blank control group (P=0.005, P<0.001). The mRNA and protein expressions of vimentin in SKOV3/DDP-RBP2i group were also lower than those in the negative control group (P=0.016, P=0.001) and the blank control group (P=0.011, P=0.001). Five weeks after the cells inoculated into the nude mice, the tumor volume of SKOV3/DDP-RBP2i group, negative control group and blank control group were statistically significant different. The tumor volume of SKOV3/DDP-RBP2i group was smaller than those of negative control group and blank control group (P=0.001). Bioinformatics analysis showed that the expression of RBP2 in patients with metastatic ovarian cancer was higher than that without metastasis (P=0.043), and the median overall survival of ovarian cancer patients with high RBP2 expression was 41 months, shorter than 69 months of low RBP2 expression patients (P<0.001). Conclusion: Downregulation of the expression of RBP2 in SKOV3/DDP cells can inhibit cell migration and invasion, and the mechanism may be related to the inhibition of EMT.
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Animals , Apoptosis , Carcinoma, Ovarian Epithelial/genetics , Cell Line, Tumor , Cell Proliferation , Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , Female , Gene Silencing , Humans , Mice , Mice, Nude , Ovarian Neoplasms/pathology , Retinol-Binding Proteins, Cellular/metabolismABSTRACT
Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.
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Objective:To assess the prognostic value of the collateral status and clot burden score based on four-dimensional computed tomography angiography(4D CTA)in anteriorcir culation is chemics troke patients with large ischemic core after endovascular treatment.Methods:Clinical and imaging data of 36 anterior circulation ischemic stroke patients with large infarct core (infarct core≥50.0 ml) after endovascular treatment at our institution from March 2016 to September 2020 were retrospectively reviewed. According to the modified Rankin Scale (mRS) score, patients were divided into the good outcome (mRS score 0-2) and poor outcome (mRS score 3-6) groups. Mann-Whitney U and Fisher tests were used to compare the 4D CTA collateral circulation score, clot burden score, and baseline clinical data between the good and poor outcome groups. Multivariate logistic regression was used to analyze the risk factors associated with the poor outcome (mRS score 3-6) and mortality in patients with large infarct core stroke. Finally, based on the 90-day outcome, a ROC curve was used to obtain the cut-off values for poor prognosis (mRS 3-6) and death, respectively. Results:Ten patients (27.8%) had good outcome and 26 (72.2%) had poor outcome. The patients in the poor outcome group had older median age, higher blood glucose, lower 4D CTA collateral circulation score, lower clot burden score, larger infarct core volume, and higher hemorrhagic transformation and brain hernia (all P<0.05). Multivariate logistic regression showed that the poor collateral circulation score on 4D CTA( OR=0.18, 95% CI: 0.03-0.99, P<0.05)and clot burden score( OR=0.64, 95% CI: 0.44-0.93, P<0.05) were independent predictors of the poor prognosis. The ROC curves revealed that the cut-off value of infarct core for distinguishing between good prognosis and poor prognosis was 63.7 ml, while that for distinguishing between survival and death was 130.3 ml. Conclusions:Endovascular treatment may improve the prognosis of patients with large infarct core of anterior circulation is chemic stroke if the patients have good 4D CTA collateral circulation score and high clot burden score.
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ObjectiveTo study the effects of different plant growth-promoting rhizobacteria （PGPR） on the growth of Paris polyphylla var. yunnanensis seedlings and the quality of its medicinal parts， in order to provide reference for the cultivation of high-quality P. polyphylla var. yunnanensis. MethodThe pot culture experiment at room temperature and the single-factor completely random design were employed for exploring the effects of five PGPR on physiological characteristics and inorganic elements of P. polyphylla var. yunnanensis. ResultThe results showed that the exogenous inoculation of different PGPR promoted the growth and development of P. polyphylla var. yunnanensis to varying degrees， delayed the senescence of leaves， and improved the medicinal value of new and old rhizomes. Compared with the non-inoculated control， the exogenous inoculation of compound microbial fertilizer （FH） and microbial agent Sanju Guanjin liquid （SJ） enhanced the root vigor， increased the content of photosynthetic pigments and the activities of anti-oxidant enzymes ［superoxide dismutase （SOD）， catalase （CAT）， and peroxidase （POD）］， and reduced the content of malondialdehyde （MDA） in leaves. Their inhibition rates against MDA were 10.46%-39.62% and 20.99%-53.12%， respectively. With the growth of P. polyphylla var. yunnanensis， the inhibition rate against MDA gradually increased， which effectively delayed the senescence of P. polyphylla var. yunnanensis leaves. In addition， the exogenous inoculation of different PGPR promoted the accumulation of nutrient elements in new and old rhizomes， lowered the heavy metal content to varying degrees， and improved the medicinal value of P. polyphylla var. yunnanensis rhizomes. ConclusionFH and SJ have exhibited the best promoting effect on the growth of P. polyphylla var. yunnanensis seedlings and also the best regulatory effect on the medicinal value of P. polyphylla var. yunnanensis rhizomes， which has provided reference for the application and promotion of PGPR in the growth of P. polyphylla var. yunnanensis.
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ObjectiveTo investigate the effect of Shunao Jieyu decoction on intestinal flora in patients with post-stroke depression. MethodSixty patients with post-stroke depression of Qi stagnation， blood stasis， and phlegm obstruction were selected and divided into a treatment group （30 cases， Shunao Jieyu decoction） and a control group （n=30， paroxetine hydrochloride tablets） according to the random number table. All patients were treated correspondingly for eight weeks. The scores of traditional Chinese medicine（TCM） syndrome， Hamilton rating scale for depression（HAMD）， National Institutes of Health stroke scale（NIHSS）， and activities of daily living（ADL）before and after treatment were compared between the two groups. High-throughput sequencing was used to analyze the diversity of fecal flora and the distribution of taxonomical levels in two groups before and after treatment. ResultThe post-treatment TCM syndrome score， HAMD score， and NIHSS score were lower than those before treatment in the same group （P<0.05）， while the post-treatment ADL score was higher than that before treatment （P<0.05）. Compared with the control group after treatment， the treatment group showed decreased TCM syndrome score （P<0.05）. No significant difference was observed in the HAMD score， NIHSS score and ADL score between the two groups after treatment. The total effective rate of the treatment group was 90% （27/30）， which was superior to 66.3% （19/30） of the control group （χ2=5.863， P<0.05）. After treatment， the average values of Chao1 index， Observed species index， Shannon index， Simpson index， and Pielou's evenness index of intestinal flora diversity in the treatment group increased without significant difference， while the average value of the Good's Coverage index remained unchanged in the same group. At the phylum level， the abundance of Bacteroidetes increased. At the family level， the abundance of Bacteroidaceae increased. At the genus level， the abundance of Bacteroidetes increased. ConclusionShunao Jieyu decoction can effectively improve the clinical TCM symptoms of patients with post-stroke depression， relieve neurological impairment， improve the ability of daily living， and change the diversity and abundance of the intestinal flora of patients at different taxonomic levels.
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ObjectiveTo explore the differences in the protective effects of five formulas for promoting blood circulation and removing blood stasis on the aortic endothelial cells of New Zealand rabbits with heart blood stasis syndrome. MethodEighty New Zealand rabbits were randomly divided into a normal group （n=10） and an experimental group （n=70）. The heart blood stasis syndrome model was induced by starvation combined with a high-fat diet and adrenaline in the rabbits of the experimental group. Subsequently， the model rabbits were randomly divided into a model group， a Xuefu Zhuyutang group （3.55 g·kg-1·d-1）， a Taohong Siwutang group （2.66 g·kg-1·d-1）， a Danshenyin group （1.962 g·kg-1·d-1）， a Huoluo Xiaolingdan group （2.80 g·kg-1·d-1）， a Shixiaosan group （0.56 g·kg-1·d-1）， and a c-Jun N-terminal kinase （JNK） inhibitor （SP600125， 5 μg·kg-1）group. The normal group and the model group received the same amount of distilled water. The rabbits in five Chinese medicine groups were treated correspondingly by gavage， and those in the SP600125 group were injected with 0.5 mL of SP600125-dimethyl sulfoxide diluent. After the treatment， the aorta was collected， and terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to detect the apoptosis of aortic endothelial cells. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was used to detect the protein expression of JNK， phosphorylated JNK （p-JNK）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cysteinyl aspartate-specific protease-9 （Caspase-9）， and cysteinyl aspartate-specific protease-3 （Caspase-3） in aortic tissues. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA levels of JNK， Bcl-2， Bax， Caspase-9， and Caspase-3 in aortic tissues. ResultFive formulas could improve the apoptosis of aortic endothelial cells to varying degrees. To be specific， Xuefu Zhuyutang and Taohong Siwutang were optimal in efficacy， followed by Huoluo Xiaolingdan， Shixiaosan， and Danshenyin， and SP600125 was the worst （P<0.05， P<0.01）. Five formulas could reduce the content of TNF-α and IL-6 （P<0.05， P<0.01）， down-regulate the protein expression levels of JNK， p-JNK， Bax， Caspase-9， and Caspase-3 （P<0.05， P<0.01）， decrease the mRNA expression levels of JNK， Bax， Caspase-9， and Caspase-3 （P<0.05， P<0.01）， and up-regulate the protein and mRNA expression levels of Bcl-2 （P<0.05， P<0.01）. ConclusionFive formulas can all reduce the apoptosis of aortic endothelial cells in New Zealand rabbits with heart blood stasis syndrome with different efficacies. It may be related to the different effects of five formulas on the JNK signaling pathway.
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Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.
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Anticoagulants/pharmacology , Blood Coagulation , Drug Design , Drugs, Chinese Herbal/pharmacology , Molecular Docking SimulationABSTRACT
Background Di(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) are representative environmental endocrine disruptors of phthalate esters (PAEs). Some studies have shown that PAEs exposure may have an impact on lipid metabolism. Objective To investigate the effects of DEHP and/or DBP on lipid metabolism in rats and their possible mechanisms of action. Methods Thirty-six weaned healthy SD male rats, 3 weeks old, weighing 50-70 g, were divided into four groups, i.e., a corn oil control group, a DEHP (750 mg·kg−1) group, a DBP (500 mg·kg−1) group, and a DEHP+DBP (750 mg·kg−1+500 mg·kg−1) group. The rats were exposed to DEHP and/or DBP by oral gavage for 8 weeks, and weighed once a week. The rats were anesthetized 24 h after the last dose, and blood was taken from the apical part of the heart. Serum high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) were detected. Liver tissues and perigenital adipose tissues were collected, weighed, and one portion of the tissues was fixed in 10% neutral formalin for pathomorphological observation, and another portion was used for mRNA detection of lipid metabolism-related genes such as Janus kinase 3 (JAK3), signal transducer and activator of transcription 5b (STAT5b), and peroxisome proliferator-activated receptor γ (PPARγ). Results During the DEHP and/or DBP exposure period, the rats in all groups were free to eat and drink without death or injury observed. Compared with the control group: The body weight gain in the DEHP+DBP group was lower at all time points from the 2nd week onwards (P<0.05); the liver organ coefficients of the DEHP and the DEHP+DBP groups were higher (P<0.05); the serum LDL-C levels in the DEHP and the DBP groups were higher (P<0.05). Compared with the DEHP+DBP group: The body weight gains in the DEHP group at the 2nd, 4th, 5th, and 8th weeks were higher (P<0.05), and the body weight gains in the DBP group were higher at all time points except the 1st week (P<0.05); the liver organ coefficients in the DEHP group and the DBP group were lower (P<0.05); the serum TG level in the DEHP group was higher(P<0.05), and the serum LDL-C levels in the DEHP and the DBP groups were higher (P<0.05). The pathomorphological results of liver tissues showed that the hepatocytes in the DEHP, DBP, and DEHP+DBP groups were disordered with loss of cord-like arrangement, swelling (suggesting change of cell proliferation), and presented bilirubin pigmentation. The pathomorphological results of rat perigenital adipose tissues showed had irregular alignment, sizes, and arrangement of adipocyte in the DEHP, DBP, and DEHP+DBP groups. The results of rat liver lipid metabolism-related gene mRNA levels showed that the liver JAK3, STAT5b, and PPARγ mRNA levels in the DEHP, DBP, and DEHP+DBP groups were lower than those in the control group (P<0.05); the rat liver PPARγ mRNA levels in the DEHP and DBP groups were lower than those in the DEHP+DBP group (P<0.05). Conclusion DEHP and/or DBP can inhibit the increase of body weight to varying degrees, induce inflammatory damage to liver tissues, and cause abnormal lipid metabolism in rats, and the associated mechanism may be related to inhibiting the activation of JAK3/STAT5b/PPARγ signaling pathway in rat liver tissues.
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Objective:To study the efficacy and safety of EndoClot polysaccharide hemostatic system (EndoClot PHS) for heparinized arterial hemorrhage of upper digestive tract (Forrest Ⅰa) in animal model.Methods:Twelve experimental pigs were randomly divided into the test group ( n=6) and the control group ( n=6) by simple random grouping method. Gastric arterial hemorrhage models were established. Endoclot PHS and Hemospray were used to spray on the wound to stop bleeding in the test group and the control group respectively. The time of effective hemostasis, the amount of hemostatic particles used, and the blockage of the powder feeding tube and its replacement were compared between the two groups. The survival and complications of experimental pigs were observed after the operation. In 10 days after the operation, the experimental pigs were euthanized for pathological dissection. Results:Spurting or pulsatile bleeding was achieved in all experimental pigs. There were significant differences in the time of effective hemostasis (8.75±0.84 min VS 9.83±0.62 min, t=-2.53, P=0.030) and the amount of hemostatic particles used to achieve effective hemostasis (6.71±0.39 g VS 14.10±1.62 g, t=-10.86, P<0.001) between the test group and the control group. There was no significant difference in the occurence of clogging or the replacement of powder feeding pipes between the two groups (0.64±0.02 times VS 0.67±0.04 times, t=-1.64, P=0.131). In addition, the gas source of the test group was stable, and the visual field under the endoscope was clear. Neither the test group nor the control group had gastric lesions, perforation, or embolism. The blood glucose, blood routine, and liver and kidney functions were normal, and no thrombosis or embolism of the main organs occurred in either group. Conclusion:EndoClot PHS is safe and effective for heparinized upper gastrointestinal arterial hemorrhage (Forrest Ⅰa) in animal models.
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Objective:Objectives The aim of the study is to evaluate the mechanical performance, safety and efficacy of the novel robotic-assistant flexible ureteroscopy system (Ra-fURS) under in vitro and in vivo environments.Methods:Combing with commercial flexible ureteroscopes, the novel Ra-fURS was used for the in vitro test and animal model operation in October 2020. The study included three sections. ①Basic mechanical performance assessment: including endoscope motion control (dual deflection, axial rotation and forward/backward distance), reaction time and fiber regulation. ②Simulated surgery in ex-vivo 3D-printing renal collecting system model: including completion rate and time of calyxes exploration, directional movement and laser fragmentation [gypsum models (0.5×0.5×0.5 cm) were used to stimulate kidney stones]. ③Intrarenal surgeries in animal models (two 5-month female Yorkshire white pigs). In total, 32 surgeries was performed (8 surgeons × 2 pigs × 2 kidneys/pig). In vivo assessments were carried out including: ①consuming time for Ra-fURS installation and offloading; ②completion rate and time of calyxes exploration; ③comfort score (ranging from 0-10) as compared to the manual f-URS, which was corresponding to each Ra-fURS surgery. In simulated surgery and animal surgery sections, 8 surgeons were enrolled in the study (group A 4 without flexible ureteroscopy experience; group B: 4 highly experienced), and results were compared between two groups.Results:Under the Ra-fURS control, the flexible ureteroscope movement in three degrees of freedom (forward / backward: + 11 to -11 cm, axial rotation + 225°to -225°; active duel-flection: + 270°to -270°, as well as the laser fiber regulation + 2.5 to -2.5 cm). In simulated surgery tests, both groups achieved 100% completion rate of calyxes exploration, and there were no statistical differences in the time of the calyxes exploration between group A and group B (116.0±8.0)s vs.(110.3±15.4)s( P>0.05). Time-consumption for laser fragmentation of group B was shorter than that of group A (525.8±58.5)s vs. (780.5±141.2)s( P<0.01). In animal surgery, the installation time of Ra-fURS gradually shortened within the first 7 cases was(234.0±43.0)s, and became comparable in the later 8-32 cases was(149.3±8.0)s. The average uninstall time was (43.9 ±5.9)s and was relatively stable. There were 51 renal calyxes in two pigs. It was higher for the completion rate of calyxes exploration in group B than in group A [(95.5±9.1)% vs. (59.1±9.1)%, P<0.05], and the exploration time was also statistically variant between the two groups group A and group B[(274.8±34.6)s vs.(127.3±18.2)s, P<0.05]. For all the operators, the comfort scores were favorable to the Ra-fURS as compared to the manual f-URS (8.9±0.3 vs. 5.9±1.1, P<0.05). Conclusions:This preliminary study demonstrated that the novel Ra-fURS was capable of controlling flexible ureteroscope to perform retrograde intrarenal surgery and fragmenting stones with laser. Besides, other features, including easy installation, stable performance and comfortable manipulating environment, made it easy to use in clinical application.
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Objective:To explore the potential application of combining 18F-FDG PET imaging and radiomics in the diagnosis of Parkinson′s disease (PD) and atypical parkinsonian syndromes (APS). Methods:A total of 154 subjects of two cohorts (training set and validation set) were enrolled from Huashan Hospital, Fudan University from March 2015 to August 2020 in this cross-sectional study, including 40 normal controls (NC; 23 males and 17 females, age: (60.2±10.5) years), 40 PD patients (20 males and 20 females, age: (64.7±6.3) years), 40 progressive supranuclear palsy (PSP) patients (20 males and 20 females, age: (64.1±5.9) years), and 34 multiple system atrophy (MSA) patients (19 males and 15 females, age: (65.0±9.2) years). 18F-FDG PET images and clinical scale were selected, and one-way analysis of variance was used to compare differences of clinical scale among groups. Radiomic features extraction and feature selection were carried out. Two and three classification models were constructed based on logistic regression, and the ROC curves of clinical model, radiomics model and combined model were calculated. Independent classification tests were conducted 100 times with 5-fold cross validation in two cohorts. Results:There were significant differences in the scores of unified PD Rating Scale (UPDRS) and Hoehn-Yahr rating scale (H&Y) among different groups in cohort 1 and cohort 2 respectively ( F values: 4.83-17.95, all P<0.05). A total of 2 444 imaging features were extracted from each subject, and after features selection, 15 features for classification were obtained. In the two classification experiment, the AUCs of the three models in binary classification of PD/MSA/PSP/NC group were 0.56-0.68, 0.74-0.93 and 0.72-0.93, respectively. The classification effects of the radiomics model were significantly better than those of the clinical model ( z values: 1.71-2.85, all P<0.05). In the three classification experiment, the sensitivity of the radiomics model reached 80%, 80% and 77% for PD, MSA and PSP, respectively. Conclusion:18F-FDG imaging combined with radiomics has potential in the diagnosis of PD and APS.
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Objective:To investigate the risk factors of infarct growth rate of elderly acute ischemic stroke(AIS)patients with endovascular treatment(EVT)and its influence on prognosis.Methods:Elderly AIS patients who underwent EVT at Beijing hospital from June 2016 to October 2020 were retrospectively included.Infarct growth rate(ml/h)=infarct core volume(ml)/time from stroke onset to CTP examination(h).Based on the rate of infarct growth and the patient's clinical severity, ROC curve was established, and the cut-off value of the ROC curve was obtained.By the cut-off value of the rate of infarct growth, the patients were divided into cerebral infarct slow-growth group and rapid-growth group.Predictors of rapid growth in infarct were analyzed by univariate and multivariate analysis.The patients were divided into good prognosis group(mRS score 0-2)and poor prognosis group(mRS score 3-6)according to the mRS score at the day 90 and the predictors of poor prognosis were analyzed separately.Results:A total of 67 elderly AIS patients were included with age ranging from 65-96 years and an average of(78.8±7.6)years.(1)The cut-off value of the optimal infarct growth rate for patients with good and poor prognosis was 8.89 ml/h.The patients were divided into fast-growth group(26 patients)and slow-growth group(41 patients)according the cut-off value.(2)Multivariate logistic regression showed that only poor collateral circulation was an independent predictor for fast infarct growth( OR=0.162, 95% CI: 0.053-0.489).(3)Faster infarct growth rate( OR=1.173, 95% CI: 1.044-1.318)and high NIHSS score( OR=1.146, 95% CI: 1.018-1.291)were predictors of poor prognosis. Conclusions:Collateral circulation status is a major influencing factor for the infarct growth rate, and a faster infarct growth rate is a predictor of poor prognosis for elderly AIS patients after endovascular treatment.
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Objective:To compare the efficacy and adverse events of induction chemotherapy combined with radiotherapy alone (IC+ RT) and induction chemotherapy combined with concurrent chemoradiotherapy (IC+ CCRT) for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy in this Meta-analysis.Methods:Retrospective or randomized controlled clinical studies published between 2010 and 2020 were searched from the Cochrane Library, PubMed, and Web of Science databases. The selected studies included nasopharyngeal carcinoma patients treated with IC+ CCRT or IC+ RT. STATA 12 software was used to combine the hazard ratio (HR), risk ratio (RR) and 95% confidence interval (CI), and random or fixed effect models were used for statistical analysis.Results:A total of 2483 patients from eight retrospective studies were included. The overall survival in the IC+ CCRT group was similar to that in the IC+ RT group ( HR=0.78, 95% CI: 0.58-1.04, P=0.091). However, the distant metastasis-free survival ( HR=0.56, 95% CI: 0.42-0.74, P<0.001) and progression-free survival ( HR=0.65, 95% CI: 0.54-0.77, P<0.001) were improved in the IC+ CCRT group compared with those in the IC+ RT group. In terms of adverse reactions, the acute adverse reactions in the IC+ CCRT group were increased significantly compared with those in the IC+ RT group. Conclusions:In the treatment of nasopharyngeal carcinoma, the overall survival of two treatment modes is similar, but the distant metastasis-free survival and progression-free survival in the IC+ CCRT group are better than those in the IC+ RT group, whereas the incidence of adverse reactions is also increased. IC+ CCRT may be a recommended treatment for nasopharyngeal carcinoma patients, but more research is needed.