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Objective: To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022. Methods: Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed. Results: A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024. Conclusion: The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.
Subject(s)
Animals , Hemorrhagic Fever with Renal Syndrome/epidemiology , Phylogeny , Orthohantavirus/genetics , Murinae , Amino Acids/genetics , VaccinesABSTRACT
Objective: To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022. Methods: Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed. Results: A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024. Conclusion: The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.
Subject(s)
Animals , Hemorrhagic Fever with Renal Syndrome/epidemiology , Phylogeny , Orthohantavirus/genetics , Murinae , Amino Acids/genetics , VaccinesABSTRACT
Objective:To explore the biomechanical stability of a novel anchor-loop internal fixation system in the treatment of acromioclavicular joint dislocation using cadaveric specimens.Methods:The acromioclavicular ligaments were severed in 12 complete shoulder joint specimens, in which the quasi-static non-destructive cycle experiment was performed until the coracoclavicular ligaments failed. The failure intensities of the coracoclavicular ligaments were recorded. Next, the 12 specimens were randomly divided into groups A, B, C and D ( n=3), in which 4 different internal fixation materials were used respectively to reduce and fix the acromioclavicular joint. Group A was subjected to 3.5 mm clavicular hook locking compression plate, group B to 5 mm soft tissue with wire anchor, group C to 10 mm Endobutton steel plate, and group D to the novel anchor-loop internal fixation system (5 mm soft tissue with wire anchor + 10 mm Endobutton steel plate). An X-ray machine was used to evaluate the reduction and internal fixation of the acromioclavicular joint. After the shoulder specimens were securely fastened by a homemade fixation jig to a 100 KN electronic universal mechanical testing machine, each experimental specimen was subjected to a destructive static tensile mechanic determination in the vertical direction at a loading speed of 100 mm/min. The load-displacement curves were recorded and drawn by a computer connected with the biomechanical testing machine. The failure strength and failure causes were recorded for each internal fixation. Results:The fracture strength of the coracoclavicular ligament in 12 cadaver specimens was (374.6±0.8) N. The mechanical load of internal fixation failure was (409.5±2.6) N in group A, (297.8±3.4) N in group B, (375.2±3.1) N in group C and (376.2±3.1) N in group D. The internal fixation failure was due to clavicular fracture in 2 specimens and to acromial fracture in 1 specimen in group A, to anchor protrusion in all the 3 specimens in group B, to coracoid base fracture in all the 3 specimens in group C, and to anchor protrusion in all the 3 specimens in group D. The mechanical loads of internal fixation failure were significantly different among the 4 experimental groups ( P<0.05). The mechanical load of internal fixation failure in group D was significantly different from that in groups A and B ( P<0.05). Conclusions:Our self-developed novel anchor-loop internal fixation system can effectively reposit the acromioclavicular joint to treat acromioclavicular joint dislocation, because it conforms to the biomechanical characteristics of the acromioclavicular joint, and is easy to handle. Therefore, its feasibility is high.
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Objective:To study the in vitro construction of functional and self-renewing cartilage organoids based on cartilage acellular extracellular matrix (ECM) microcarriers.Methods:Fresh porcine articular cartilage was taken. The merely crushed cartilage particles were set as natural cartilage group and ECM microcarriers of appropriate particle size, which were prepared by the acellular method of combining physical centrifugation and chemical extraction, were set as microcarrier group. Cartilage organoids were constructed by loading human umbilical cord mesenchymal stem cells (hUCMSCs) and human chondrocytes (hCho) with a ratio of 3∶1 with microcarriers through a rotating bioreactor. The organoids with different induction times were divided into 0-, 7-, 14-, and 21-day induction groups. The cell residues of the microcarrier group and natural cartilage group were evaluated by 4′, 6-diaminidine 2-phenylindole (DAPI) fluorescence staining and DNA quantitative analysis. The retention of microcarrier components was observed by Safranin O and toluidine blue stainnings, and the collagen and glycosaminoglycan (GAGs) levels in the microcarrier group and the natural cartilage group were determined by colorimetric method and dimethyl-methylene blue (DMMB) method. The microcarriers were further characterized by scanning electron microscopy and energy dispersive spectroscopy. The hUCMSCs cultured with Dulbecco′s Modified Eagle′s Medium (DMEM) supplemented with fetal bovine serum (FBS) in a volume fraction of 10% was used as the control group and the hUCMSCs cultured with the microcarrier extract was used as the experimental group. Subgroups of hUCMSCs cultured at 3 time points: 1, 3 and 5 days were set up in the two groups separately. Cell Counting Kit 8 (CCK-8) was used to detect the biocompatibility of the two groups. The cellular activity of the organoids of the 0-, 7-, 14-, and 21-day induction groups was detected by live/dead staining and the self-renewal ability of the cartilage organoids of the 14-day induced group was identified by Ki67 fluorescence staining. The organoids of the 7-, 14-, and 21-day induction groups were detected by RT-PCR in terms of the expression levels of chondrogenesis-related marker aggrecan (ACAN), type II collagen (COL2A1), SRY-related high mobility group-box gene-9 (SOX9), cartilage hypertrophy-and mineralization-related marker type I collagen (COL1A1), Runt-related transcription factor-2 (RUNX2), and osteocalcin (OCN). Colorimetric and DMMB assays were performed to determine the ability of organoids in the 0-, 7-, 14-, and 21-day induction groups to secrete collagen and GAGs.Results:The results of DAPI fluorescent staining showed that the natural cartilage group had a large number of nuclei while the microcarrier group hardly had any nuclei. The DNA content of the microcarrier group was (7.8±1.8)ng/mg, which was significantly lower than that of the natural cartilage group [(526.7±14.7)ng/mg] ( P<0.01). Saffranin O and toluidine blue staining showed that the microcarrier was dark- and uniform-colored and it kept a lot of cartilage ECM components. The collagen and GAGs contents of the microcarrier group were (252.9±1.4)μg/mg and (173.4±0.8)μg/mg, which were significantly lower than those of the natural cartilage group [(311.9±2.2)μg/mg and (241.3±0.7)μg/mg] ( P<0.01). Scanning electron microscopy showed that the surface of the microcarriers had uneven and interleaved collagen fiber network. The results of energy spectrum analysis showed that elements C, O and N were evenly distributed in the microcarriers, indicating that the composition of the microcarrier was uniform. The microcarrier had good biocompatibility and there was no statistical significance in the results of CCK-8 test between the control group and the experimental group after 1 and 3 days of culture ( P>0.05). After 5 days of culture, the A value of the experimental group was 0.53±0.02, which was better than that of the control group (0.44±0.03) ( P<0.05). In the 0-, 7-, 14-, and 21-day induction groups, hUCMSCs and hCho were attached to the surface of the microcarriers, with good cellular activity, and the live/death rates were (70.6±1.1)%, (80.5±0.6)%, (94.5±0.9)%, and (90.8±0.5)% respectively ( P<0.01). There were a large number of Ki67 positive cells in cartilage organoids. RT-PCR showed that the expression levels of ACAN, COL2A1, SOX9, COL1A1, RUNX2 and OCN were 1.00±0.09, 1.00±0.24, 1.00±0.18, 1.00±0.03, 1.00±0.06 and 1.00±0.13 respectively in the 7-day induction group; 4.16±0.28, 5.09±1.25, 5.65±1.05, 0.47±0.01, 1.68±0.02 and 0.21±0.06 respectively in the 14-day induction group; 13.42±0.92, 3.07±0.21, 1.84±1.08, 2.72±0.17, 2.91±0.18 and 3.32±1.20 respectively in the 21-day induction group. Compared with the 7-day induction group, the expression levels of ACAN, COL2A1, SOX9 and RUNX2 in the 14-day group were increased ( P<0.05), but COL1A1 expression level was decreased ( P<0.05), with no significant difference in OCN expression level ( P>0.05). Compared with the 7-day induction group, the expression levels of ACAN, COL1A1 and RUNX2 in the 21-day induction group were significantly increased ( P<0.01), with no significant differences in the expression levels of COL2A1, SOX9 and OCN ( P>0.05). Compared with the 14-day induction group, the expression levels of ACAN, COL1A1, RUNX2 and OCN in the 21-day group were increased ( P<0.05 or 0.01), with no significant difference in the expression level of COL2A1 ( P>0.05), but the expression level of SOX9 was decreased ( P<0.05). The contents of collagen in 0-, 7-, 14-and 21-day induction groups were (219.15±0.48)μg/mg, (264.07±1.58)μg/mg, (270.83±0.84)μg/mg and (280.01±0.48)μg/mg respectively. The GAGs contents were (171.18±1.09)μg/mg, (184.06±1.37)μg/mg, (241.08±0.84)μg/mg and (201.14±0.17)μg/mg respectively. Compared with the 0-day induction group, the contents of collagen and GAGs in 7-, 14-, and 21-day induction groups were significantly increased ( P<0.01), among which the content of collagen was the lowest in 7-day induction group ( P<0.01) but the highest in the 21-day induced group ( P<0.01); the content of GAGs was the lowest in the 7-day induced group ( P<0.01) but the highest in the 14-day induction group ( P<0.01). Conclusions:The microcarriers prepared by combining physical and chemical methods are decellularized successfully, with more matrix retention, uniform composition and on cytotoxicity. By loading microcarriers with hUCMSCs and hCho, cartilage organoids are successfully constructed in vitro, which are characterized by good cell activity, self-renewal ability, strong expression of genes related to chondrogenesis and secretion of collagen and GAGs. The cartilage organoids constructed at 14 days of induction have the best chondrogenic activity.
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Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.
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Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ2=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ2=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ2=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Subject(s)
Male , Female , Child , Humans , Child, Preschool , Leukemia, Myelomonocytic, Juvenile/therapy , Retrospective Studies , Survival Analysis , Mutation , Hematopoietic Stem Cell TransplantationABSTRACT
Objective:To explore the value of pre-ablation stimulated thyroglobulin (psTg) before 131I treatment combined with lymph node ratio (LNR) in predicting 131I treatment response in patients with papillary thyroid cancer (PTC). Methods:From January 2016 to December 2018, 178 PTC patients (47 males, 131 females; age (43.2±12.6) years) treated with 131I in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. According to 131I treatment response, patients were divided into excellent response (ER) group and non-ER group. The clinical data of the two groups were compared by χ2 test, independent-sample t test and Mann-Whitney U test. The cut-off values and AUCs of psTg and LNR to predict treatment response were calculated according to the ROC curve. Factors affecting 131I treatment response were analyzed by logistic multivariate regression analysis. Results:There were 118 patients (66.3%, 118/178) in ER group and 60 patients (33.7%, 60/178) in non-ER group, and there were significant differences in N stage ( χ2=11.15, P=0.004), 131I treatment dose ( χ2=12.65, P<0.001), American Thyroid Association (ATA) initial risk stratification ( χ2=15.25, P<0.001), number of metastatic lymph nodes ( χ2=22.63, P<0.001), LNR ( U=1 506.00, P<0.001) and psTg ( U=919.00, P<0.001) between the two groups. The cut-off values of psTg and LNR predicting ER were 3.97 μg/L and 0.29, with the AUC of 0.870 and 0.787 respectively. PsTg (odds ratio ( OR)=10.88, 95% CI: 4.67-25.36, P<0.001) and LNR ( OR=5.30, 95% CI: 1.85-15.23, P=0.002) were independent factors to predict 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR ( OR=9.40, 95% CI: 2.06-42.92, P=0.004) was an independent factor affecting 131I treatment response in PTC patients. Conclusions:PsTg and LNR are independent factors affecting 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR can be used as a supplementary factor to predict 131I treatment response. The combination of psTg and LNR can better predict 131I treatment response in PTC patients.
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Objective To design a surgical micro-instrument based on flexible cable actuation and perform simulation analysis to eliminate the influences of the traditional surgical instruments on the precise operation of minimally invasive surgical procedures.Methods Firstly,the configuration design of the surgical micro-instrument was implemented based on the elastic element and flexible cable actuation,and the layout of the flexible cable was determined to optimize the flexible cable transmission mode.Secondly,the forward and inverse kinematic model of the surgical micro-instrument was constructed based on D-H method and then validated using MATLAB,and the workspace and singular shapes of the surgical micro-instrument were analysed.Finally,multi-case kinetic simulation analysis of the surgical micro-instrument was performed in conjunction with soft-tissue mechanical response,and sensitivity analysis of the effect of instrument-tissue interaction forces on joint driving torque was carried out.Results The surgical micro-instrument developed gained advantages in the accuracy of the forward and inverse kinematic model,the workspace and singular shapes for meeting surgical requirements and the sensitivity of joint driving torque for instrument-tissue interaction forces.Conclusion The surgical micro-instrument designed keeps the flexible cable in a tension state so as to satisfy the requirements for precision manipulation during actual minimally invasive surgery.
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Measurement bias (MB) has been described in causal structures but is still not entirely clear. In practice, the correctness of substitution estimate (SE) of effect is a prerequisite for causal inference, usually based on a bidirectionally non-differential misclassification between the measured exposure and the measured outcome. Based on a directed acyclic graph (DAG), this paper proposes a structure for the single-variable measure, where its MB is derived from the choice of an imperfect, "input/output device-like" measurement system. The MB of the SE is influenced both by the measurement system itself and by factors outside the measurement system: while the independence or dependence mechanism of the measurement system still ensures that the MB of the SE is bidirectionally non-differential; however, the misclassification can be bidirectionally non-differential, unidirectionally differential, or bidirectionally differential resulted from the factors outside the measurement system. In addition, reverse causality should be defined at the level of measurement, where measured exposures can influence measured outcomes and vice versa. Combined with temporal relationships, DAGs help elucidate MB's structures, mechanisms, and directionality.
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Humans , Confounding Factors, Epidemiologic , Data Interpretation, Statistical , Bias , CausalityABSTRACT
AIM: To measure the indexes including postoperative distance, middle, near visual acuity and near stereopsis vision of patients with high myopia cataract and corneal astigmatism by femtosecond laser, which can quantify the diameter of capsulorhexis opening, and to evaluate the availability and necessity of Toric intraocular lenses(IOL)in high myopia.METHODS: Prospective case-control study. Patients with binocular high myopia cataract and corneal astigmatism who undergone femtosecond laser-assisted cataract surgery in our hospital were selected, and they were divided into two groups, with 20 cases(40 eyes)in group A(Toric IOL)and 20 cases(40 eyes)in group B(IQ IOL). Indexes, including preoperative corneal astigmatism and spherical equivalent and best-corrected distance visual acuity, uncorrected middle visual acuity, uncorrected near visual acuity, residual refractive astigmatism, near stereopsis acuity, total high-order aberration and total spherical aberration, were measured postoperatively at 7d, 1 and 3mo.RESULTS: The uncorrected middle and near visual acuity, Titmus near stereopsis acuity and residual astigmatism at 7d, 1 and 3mo after surgery were significantly improved in the Toric IOL group than the non-Toric group(all P&#x003C;0.05). The dependence on glasses was reduced. The postoperative best-corrected distance visual acuity, total high-order aberration and total spherical aberration of the two groups showed no statistically significant differences(all P&#x003E;0.05).CONCLUSIONS: The implantation of Toric IOL in patients with high myopia cataract and corneal astigmatism can effectively correct corneal astigmatism, improve postoperative uncorrected middle and near visual acuity and near stereopsis visual function, reduce postoperative dependence on glasses and enhance binocular stereopsis visual function.
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Objective@#To explore the differences of sensory manifestations between ASD children and typical development children, and to clarify the characteristics of sensory abnormalities in ASD and their relationship with various clinical symptoms, so as to provide scientific basis for early identification and specific intervention.@*Methods@#A total of 265 ASD children who received rehabilitation training in autism rehabilitation institutions in Heilongjiang Province were collected as the case group, and 223 typical development children in ordinary kindergartens and schools in Harbin were taken as the control group. Short Sensory Profile (SSP) was used to evaluate the difference of children s sensory perception level between the two groups, and Social Response Scale (SRS) and Autism Behavior Checklist (ABC) were used to evaluate the severity of symptoms including social disorder of autistic children. The correlation between SSP scores in ASD group and clinical scales was analyzed.@*Results@#The comparison of SSP scores between the two groups found that the median scores of all sensory dimensions in ASD group (tactile=33, taste/smell=18, motion sensitivity=13, Low response/sensation seeking=28, auditory filtering=19, low strength=22, visual/auditory=20) were lower than those of the healthy control group( Z =-2.73,-4.36,-3.17,-5.09,-11.00,-10.45,-3.43, P <0.05). The abnormal rate of multisensory score in children in ASD group was 55.1%, and that in control group was 21.2%, with significant difference( χ 2=57.15, P <0.05). Correlation analysis showed that SSP score in ASD group was negatively correlated with all dimensions of SRS, nonverbal communication, and social function of ADI-R scale, ADOS communication and social interaction, and total scores of ABC and CARS( P < 0.05 ).@*Conclusion@#Children with ASD have atypical sensory experiences, especially in auditory filtering dimension, and the level of atypical sensation is related to the severity of clinical symptoms of autism. In the future clinical diagnosis, treatment and research, it is necessary to strengthen the ability to recognize the sensory symptoms of children with ASD, so as to realize the early diagnosis and intervention.
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Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".
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Objective:To explore the impact of half-dose 18F-FDG on the image quality in infants and toddlers undergoing total-body PET/CT. Methods:From January 2021 to August 2023, 59 infants and toddlers undergoing total-body 18F-FDG PET/CT scans at Sun Yat-Sen University Cancer Center were retrospectively enrolled. Of these, 21 patients (11 males, 10 females; age: 22.0(7.5, 34.5) months) were given a full dose of 18F-FDG (3.70 MBq/kg), and the other 38 patients (24 males, 14 females; age: 20.0(9.3, 33.3) months) received half dosage (1.85 MBq/kg) both with 10-minute scans. The differences of image quality scores and quantitative parameters including SUV, standard deviation (SD) of SUV, signal-to-noise ratio (SNR), and the normalized SNR for administered activity and scan time (SNR norm) were compared between the two groups by Mann-Whitney U test. The correlations between age, body weight and image quality were analyzed by Spearman rank correlation analysis. Results:The injected dosage of 18F-FDG for the full-dose group was 46.99(27.75, 50.42) MBq, while for the half-dose group was 21.83(18.13, 28.86) MBq. Compared to the full-dose group, the half-dose group had higher SD in the mediastinal blood pool (0.04(0.03, 0.05) vs 0.05(0.04, 0.08); z=-2.32, P=0.021). No statistically significant differences were observed between the two groups in terms of other SUV parameters ( z values: from -1.92 to -0.48, all P>0.05). In terms of image quality, the liver SNR of full-dose group was 29.5(25.3, 39.9), while that of half-dose group was 25.8(22.0, 30.4), with no significant difference ( z=1.66, P=0.096). The SNR values of mediastinal blood pool showed the same comparing result (20.0(11.4, 31.0) vs 19.0(11.4, 31.0); z=0.02, P=0.981). The correlation analysis revealed that SNR norm decreased with increasing age and body weight ( rs values: -0.704, -0.647, both P<0.001). Conclusions:In infants and toddlers, half-dose 18F-FDG total-body PET/CT with 10-minute scan can still achieve good performance. There is an observed decline in image quality with increasing age and body weight.
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The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.
Subject(s)
Humans , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Molecular Docking Simulation , Network Pharmacology , Drugs, Chinese Herbal/pharmacology , Capsules , Atherosclerosis , Cerebral Infarction , NeoplasmsABSTRACT
Objective: To analyze the treatment and clinical prognosis of lower extremity arterial injury caused by trauma. Methods: The clinical data of 77 patients with traumatic lower extremity arterial injury admitted to Department of Vascular Surgery,Yichang Central People's Hospital from January 2013 to June 2021 were collected retrospectively. There were 65 males and 12 females, with an average age of 47.4 years (range: 7 to 75 years). Among the 77 patients, 56 cases (72.7%) had open injury and 21 cases (27.3%) had closed injury. Iliac artery was injured in 9 cases (11.7%), common femoral artery in 7 cases (9.1%), superficial femoral artery in 1 case (1.3%), popliteal artery in 11 cases (14.3%) and inferior knee artery in 49 cases (63.6%). The treatment methods and clinical effects were analyzed. Results: One case with pelvic fracture combined the internal iliac artery injury and 1 case with multiple injuries involving the common femoral artery died of circulatory failure before surgery. Seventy-five cases received vascular-related operations, including arterial ligation in 24 cases, arterial reconstruction in 40 cases, stent graft implantation in 1 case, primary amputation in 2 cases, and arterial embolization in 8 cases. The overall mortality rate was 6.5% (5/77), all of which were closed injuries. Except for 2 cases who died before surgery, 3 cases with pelvic fracture combined the internal iliac artery injury died of multiple organ failure after internal iliac artery embolization. There were 8 cases received amputation (10.4%, 8/77), 5 cases with closed injury and 3 cases with open injury. In addition to 2 cases with primary amputation, 6 cases underwent secondary amputation due to ischemia-reperfusion injury after revascularization (4 cases with popliteal artery injury and 2 cases with subpatellar artery injury). The average followed-up time was 17 months (range: 2 months to 8 years). One patient with femoral artery injury underwent autologous great saphenous vein bypass, and lower limb artery CT angiography was re-examined 6 months after the operation, and 30% distal anastomotic stenosis was found. Ankle brachial index<0.8 was found in two patients 1 year after popliteal artery repair, but none of the patients had intermittent claudication symptoms, and no further intervention was performed. Five patients suffered delayed healing due to severe lower limb injury, fracture and skin injury. Among them, 2 cases had poor wound healing at the stump of amputation, which gradually healed 3 to 5 months after several debridements. The other 3 vascular injury combined with tibial fracture patients had delayed tibial healing after surgery, but no symptoms of vascular ischemia occurred. All the other patients recovered well and no other serious complications occurred. Conclusions: The proportion of death and disability in patients with lower limb artery injury caused by trauma is high. Active and orderly surgical repair according to the site and type of injury can reduce the mortality, save the function of the affected limb, and promote the healing of injury.
Subject(s)
Female , Humans , Male , Middle Aged , Amputation, Surgical , Femoral Artery , Lower Extremity , Popliteal Artery/surgery , Retrospective Studies , Treatment Outcome , Vascular System Injuries/surgeryABSTRACT
AIM:To investigate the effect of bromodomain-containing protein 4(BRD4)inhibitors on the via-bility and apoptosis of activated B cell-like diffuse large B-cell lymphoma(ABC-DLBCL)cells and the molecular mecha-nism. METHODS:The ABC-DLBCL cells were treated with BRD4 inhibitors JQ1 and I-BET-762,and Bruton tyrosine kinase(BTK)inhibitor ibrutinib. The viability and death of the cells were determined by CCK-8 assay and PI staining,re-spectively. The mRNA levels of BTK,phospholipase Cγ(PLCγ),LYN,SYK,interleukin-6(IL-6),MYC,protein ki-nase Cβ(PKCβ),mucosa-associated lymphoid tissue lymphoma translocation protein 1(MALT1),MYC and RELA were detected by real-time PCR. The protein levels of BTK,PLCγ,MYC and RELA were determined by Western blot. Super-enhancer around BTK gene was revealed by bioinformatics analysis. RESULTS:The ABC-DLBCL cells were sensitive to BRD4/super-enhancer inhibitors such as JQ1 and I-BET-762. Both JQ1 and I-BET-762 inhibited the chronic active B-cell receptor(BCR)/nuclear factorκB(NFκB)signaling through reducing the transcription of BTK,but they had minimal ef-fect on other components in BCR/NFκB signaling. Interestingly,there was no super-enhancer around BTK gene,and the inhibitory effect of JQ1 was likely due to disruption of BRD4 binding within BTK gene. Inhibition of BRD4 had synergic ef-fect with BTK inhibitor ibrutinib. Moreover,inhibition of BRD4 induced significant cell death in ibrutinib-resistant ABC-DLBCL cells. CONCLUSION:Inhibitors of BRD4 induce ABC-DLBCL cell death via blocking BCR/NFκB signaling and has synergic effect with BTK inhibitor. Inhibition of BRD4 might be a promising strategy for treatment of ABC-DLBCL,es-pecially ibrutinib-resistant ABC-DLBCL.
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OBJECTIVES@#To investigate the genetic information of 57 autosomal InDel loci (A-InDels) included in AGCU InDel 60 fluorescence detection kit in the Beichuan Qiang population of Sichuan Province and evaluate its application value in forensic medicine.@*METHODS@#A total of 200 unrelated healthy individuals from Beichuan Qiang population of Sichuan Province were typing detected by AGCU InDel 60 fluorescence detection kit. Allele frequencies and population genetic parameters of the 57 A-InDels were statistically analyzed and compared with the available data of 26 populations.@*RESULTS@#After Bonferroni correction, there was no linkage disequilibrium between the 57 A-InDels, and all loci were in Hardy-Weinberg equilibrium. Except for rs66595817 and rs72085595, the minor allele frequencies of 55 A-InDels were above 0.3. PIC ranged from 0.298 3 to 0.375 0, CDP was 1-2.974 8×10-24, CPEduo was 0.999 062 660, and CPEtrio was 0.999 999 999. The calculation of the genetic distance showed that Beichuan Qiang population had the closest genetic distances with Beijing Han and South China Han populations, but far away from African populations.@*CONCLUSIONS@#The 57 A-InDels in AGCU InDel 60 fluorescence detection kit have a good genetic polymorphism in Beichuan Qiang population of Sichuan Province, which can be used as effective supplemental for individual identification and paternity identification in forensic medicine.
Subject(s)
Humans , Genetics, Population , Asian People/genetics , Polymorphism, Genetic , Gene Frequency , INDEL Mutation , China , Microsatellite Repeats , Genetic LociABSTRACT
Objective:To evaluate the kinetic metrics changes of FDG in key organs after chemo-immunotherapy in patients with locally advanced non-small cell lung cancer (NSCLC) identified by total-body PET/CT dynamic imaging, and explore its potential biological significance.Methods:From August 2020 to March 2021, 16 patients (13 males, 3 females; age: 43-67 years) with locally advanced NSCLC who underwent total-body 18F-FDG PET/CT dynamic imaging in Sun Yat-sen University Cancer Center were retrospectively analyzed. ROIs of key organs were drawn at baseline and after chemo-immunotherapy to obtain the time-activity curves (TACs). The kinetic metrics, including K1, k2, k3 and metabolic rate of FDG (MR FDG), were fitted by the two-tissue compartment model. Paired t test or Wilcoxon signed rank test was used to compare the differences of FDG kinetic parameters in each organ before and after treatment. Results:Compared with baseline, SUV max of colon (3.23±1.29 vs 4.81±2.73), MR FDG ((2.77±1.96) vs 3.56(1.07, 9.89) μmol·100 g -1·min -1) of lungs, SUV max (2.16±0.27 vs 2.33±0.41), k3 ((0.008±0.002) vs (0.012±0.004) min -1) and MR FDG ((2.65±0.81) vs (3.76±1.59) μmol·100 g -1·min -1) of spleen, and SUV max (2.59±0.45 vs 4.49±2.73), k2 ((0.76±0.37) vs (1.27±0.66) min -1), k3 ((0.032±0.007) vs (0.066±0.029) min -1) and MR FDG ((5.14±1.44) vs (8.39±2.67) μmol·100 g -1·min -1) of bone marrow were increased after chemo-immunotherapy with significant differences ( t values: from -5.40 to 3.47, z=-2.02, all P<0.05). There were no significant differences of SUV max, k values and MR FDG in other organs ( t values: from -2.00 to 2.35, z values: from -1.45 to -0.05, all P>0.05). Conclusions:After chemo-immunotherapy, the activation of immune system may be manifested as the increase of FDG kinetic rate constants in spleen and bone marrow. The lung and colon may be target organs for immune-related adverse effects.
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Objective:To observe the changes in peripapillary vessel perfusion after uncomplicated phacoemulsification surgery in patients with cataract and primary open-angle glaucoma (POAG).Methods:A case-control study. From November 2017 to April 2019, 17 eyes of 17 cases of POAG complicated with cataract (observation group) and 17 eyes of 17 cases of simple senile cataract (control group) were included in the study. All the affected eyes underwent best corrected visual acuity (BCVA), intraocular pressure (IOP), visual field, optical coherence tomography angiography (OCTA) examination, and measurement of axial length (AL) and central corneal thickness (CCT). All eyes underwent conventional phacoemulsification surgery for cataract. After the operation, the same equipment and methods as before the operation were used for related inspections. The VD, the thickness of the retinal nerve fiber layer (RNFL), and the IOP were observed before the operation, at the end of the operation, and 1 d, 1 week, 1 month and 3 months after the operation, mean visual field defect (MD) changes 3 months after surgery. Data comparisons within groups used repeated measures analysis of variance; data comparisons between groups used independent samples t test. Results:The average age of patients in the observation group and control group was 68.18±6.13 and 65.82±6.95 years, respectively, and the difference was not statistically significant ( t=1.912, P=0.072). There was no significant difference in AL ( t=1.436), CCT ( t=-1.557) and phacoemulsification ( t=1.602) between the two groups ( P>0.05). The difference of the mean IOP was statistically significant between the two groups ( t=4.139, P<0.05). Before surgery, the VD ( t=-6.560) and RNFL thickness ( t=-7.320) of the observation group were lower than those of the control group, and the difference was statistically significant ( P<0.05). Compared with before the operation, the VD around the disc of the eye in both groups increased at the end of the operation and at different time points after the operation. Among them, the observation group had a statistically significant difference at 1 month after the operation of the eye ( F=3.108, P=0.042); the control group had no significant difference at different time points after the operation ( F=1.981, P>0.05). The results of each quadrant analysis showed that only the observation group had a statistically significant difference in the temporal side of the eye one month after surgery ( F=5.414, P=0.017). After surgery, the observation group and the control group had thicker RNFL thickness around the disc of the eye, and the difference was statistically significant ( F=22.670, 23.080; P=0.002, 0.001). Before the operation and 3 months after the operation, the average MD of the eyes of the observation group and the control group were 14.90±7.15, 1.12±0.93 dB and 12.10±7.70, 0.88±0.66 dB, respectively. The average MD before and 3 months after the operation was compared, and the difference was statistically significant ( t=14.414, 13.225; P=0.000, 0.000). Compared with before surgery, there was no statistically significant difference in the average MD of the two groups of eyes at 3 months after surgery ( t=0.938, 0.817; P=0.082, 0.103). At the end of the operation, the intraocular pressure of the observation group and the control group were 10.84±3.39 and 11.46±3.79 mm Hg (1 mm Hg=0.133 kPa), respectively; they were both lower than before the operation, and the difference was statistically significant ( t=-2.211, -2.310; P<0.05). Conclusions:The thickness of VD and RNFL in eyes with POAG combined with cataract is lower than that in patients with senile cataract alone. The high perfusion pressure during conventional phacoemulsification surgery can cause a transient increase in VD, but it will not cause further damage to the visual field of POAG patients.
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Objective:To explore the relationship between executive functioning and community integration after a traumatic brain injury and to identify the main factors influencing community integration.Methods:A cross-sectional study of 30 traumatic brain injury survivors was conducted recording their gender, age, years of education, days in coma, living status and mobility. Their executive functioning was assessed using the Disorders of Executive Function Questionnaire (DEX) and the Wisconsin Card Sorting Test (WCST). Their community integration was evaluated using the Community Integration Questionnaire (CIQ). The independent correlations of demographic characteristics, life status, mobility and executive functioning with CIQ score were quantified.Results:The average total CIQ score was negatively correlated with the average WCST-RP, DEX and WCST-RPE scores, but it was positively correlated with mobility. It was also significantly correlated with life status. DEX scores and WCST-RP scores were significant independent predictors of community integration. The average CIQ family integration score was negatively correlated with days spent in a coma and significantly correlated with living status. The average CIQ social integration score was positively correlated with mobility (and negatively correlated with DEX, WCST-RP and WCST-RPE score. WCST-RP score and mobility were significant independent predictors of CIQ social integration scores. The average CIQ productive activity scores correlated negatively with the DEX, WCST-RP and WCST-RPE scores, and with the DEX and WCST-RP executive function scores. They were significant independent predictors of CIQ productive activity scores.Conclusions:Executive functioning can predict community integration, especially its social integration dimension.