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Objective:To evaluate the efficacy and safety of vedolizumab (VDZ) in the treatment of active ulcerative colitis (UC).Methods:From November 1, 2020 to October 30, 2022, at the Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, 81 UC patients who received VDZ treatment and completed a 14-week follow-up were retrospectively selected. The clinical data of patients, including age, disease duration, disease activity of UC were collected. The VDZ efficacy evaluation included primary and secondary efficacy indicators. The primary efficacy indicator was the clinical remission rate after 14 weeks of VDZ treatment, and the secondary efficacy indicators included the clinical response rate, steroids-free remission rate, endoscopic remission rate after 14 weeks of treatment as well as the clinical response rate, clinical remission rate, steroids-free remission rate, secondary loss of response rate after 52 weeks of treatment. The adverse reactions during the treatment were recored. Taking clinical remission after 14 weeks of treatment as the dependent variable, univariate analysis was performed to identify the risk factors affecting clinical remission of VDZ. Binary logistic regression analysis was used for multivariate analysis to determine the independent risk factors of VDZ-included clinical remission. Chi-square test and Wilcoxon signed-rank test were used for statistical analysis.Results:Among the 81 UC patients, the age was 40.0 years old (29.0 years old, 53.5 years old) and the disease duration was 42.5 months (22.5 months, 94.7 months). The proportion of patients with mild active UC was 21.0% (17/81), the proportion of patients with moderate active UC was 64.2% (52/81), and the proportion of patients with severe active UC was 14.8% (12/81). After 14 weeks of treatment, the total Mayo score decreased from baseline level of 7.0 (6.0, 9.0) to 1.0 (0.0, 3.0), and the difference was statistically significant ( Z=-6.87, P<0.001). The clinical response rate was 84.0% (68/81) and the clinical remission rate was 69.1% (56/81) after 14 weeks of treatment. Of the 17 patients treated with combination of corticosteroid therapy, 10 achieved steroid-free remission, and the endoscopic remission rate was 34.8% (23/66). Of the 43 patients followed up to 52 weeks, the total Mayo score of UC patients decreased from baseline level of 7.0 (6.0, 9.0) to 0.0 (0.0, 1.0) after 52 weeks of treatment, and the difference was statistically significant ( Z=-3.25, P<0.001). The clinical response rate was 69.8% (30/43), and the clinical remission rate was 65.1% (28/43). Of the 13 patients treated with combination of corticosteroid therapy, 10 patients achieved steroid-free remission. The secondary loss of response rate was 15.2%(5/33) .The result of the univariate analysis showed that previous use of glucocorticoids was a risk factor of clinical remission after 14 weeks of VDZ treatment ( χ2=5.88, P=0.015). The result of multivariate logistic regression analysis showed that previous use of glucocorticoids was an independent risk factor of clinical remission after 14 weeks of VDZ treatment ( OR=3.429, 95% confidence interval 1.235 to 9.517, P=0.014). During the follow-up period, 12.3% (10/81) of patients developed Clostridium difficile infections, except for 1 case stopped VDZ treatment because the clinical response was not reached, remaining 9 cases continued VDZ treatment after received anti- Clostridium difficile treatment. Conclusion:VDZ has good clinical efficacy and safety in the treatment of Chinese UC patients, and patients with no history of glucocorticoid use may be more likely to achieve clinical remission after 14 weeks of treatment.
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Objective:To investigate the combination of internal fixation for periprosthetic fractures of the proximal femur (PFFF) after hip arthroplasty.Methods:The data of 58 patients with periprosthetic fractures after hip arthroplasty from May 2008 to March 2022 were retrospectively analyzed, including 31 males and 27 females. The average age was 75.5±18.2 years (range, 35-95 years). There were 39 total hip arthroplasty and 19 hemiarthroplasty; 37 biological prosthesis and 21 cemented prosthesis. Intraoperative periprosthetic fractures occurred in 6 cases and 52 cases postoperatively. Unified classification system (UCS): UCS IV.3A1 type 2 cases, 3A2 type 1 case, 3B1.1 type 19 cases, 3B2.1 type 25 cases, 3B3 type 2 cases, 3C type 9 cases. Fracture site: 3 cases in zone A (greater trochanter), 46 cases in zone B (around the femoral stem), and 9 cases in zone C (distal to the tip of the femoral stem. Internal fixation is composed of primary and secondary fixation, the main fixation method was the cerclage of steel wire or titanium cable, locking compression plate, and locking attachment plate fixation. The secondary fixation method was the cerclage of titanium cable, which was required to cover three zones A, B and C to form an overall balanced fixation. The modified Harris hip scores (mHHS), plate length, working length and screw number of different internal fixation combinations were compared.Results:The follow-up time was 54.2±21.6 months (range, 11-86 months). All patients showed signs of fracture healing at 10.2±1.5 weeks (range, 7-13 weeks) after operation, and bony union was observed at 19.6±1.3 weeks (range, 17-22 weeks) after operation. No delayed union or nonunion was observed. After operation, one case had a stress fracture and was revised with double-plate internal fixation; one case had a failed internal fixation and was revised with double-plate internal fixation and a large allograft bone graft. The mHHS score of UCSIV.3B2.1 group (80.3±4.6) was the lowest at 6 months after operation, and the difference between the groups of different types was statistically significant ( F=256.72, P<0.001). The score of simple internal fixation group (91.6±4.2) was higher than that of revision combined with internal fixation group (81.9±4.1), and the difference was statistically significant ( t=8.32, P<0.001). The plate length and working length were 24.9±2.5 cm and 12.6±1.7 cm for UCS IV.3B1.1, 25.4±2.6 cm and 13.6±1.8 cm for 3B2.1 and 28.1±2.5 cm and 4.9±1.9 cm for 3C, respectively ( F=5.33, P=0.005; F=6.78, P<0.001). The number of screws in zone A was significant difference among different UCS types ( F=52.67, P<0.001); UCS IV.3B1.1 (6.5±2.3) and 3B2.1 (6.7±2.2) were more than 3B3 (3.5±1.5) and 3C (3.7±1.6). The number of screws in zone B was significant difference among different UCS types ( F=42.15, P<0.001); The number of UCS IV.3B1.1 (2.3±1.6) and 3B2.1 (2.8±1.9) were significantly more than that of 3B3 (1.0±0.5) and 3C (1.2±0.6). The number of screws in zone C was significant differences among different UCS types ( F=39.62, P<0.001); The number of UCS IV.3B1.1 (3.8±1.9) and 3B2.1 (3.9±1.7) were more than that of 3B3 (2.0±0.5), the difference was statistically significant ( P<0.05). Conclusion:The function of hip after simple internal fixation of proximal femoral periprosthetic fractures was better than that of those who underwent revision at the same time; the number of screws of UCSIV.B1 and B2 is more than that of B3.
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Background@#Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. @*Methods@#We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. @*Results@#In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing.Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. @*Conclusion@#This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.
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@#Objective To investigate short-term outcomes of robot-assisted Heller-Dor myotomy (RAHM-Dor) for achalasia of cardia and our learning curve experience. Methods The clinical data and recent follow-up results of 42 patients who received RAHM-Dor from November 2015 to January 2020 in the Department of Thoracic Surgery of the First Affiliated Hospital of Nanchang University were retrospectively analyzed, including 20 males and 22 females with a mean age of 40.8±18.4 years. Results Dysphagia was the most common symptom, followed by heartburn and regurgitation. The mean operation time was 122.8±23.9 min. The mean blood loss was 47.5±32.7 mL. Two patients suffered mucosal injury, and successfully repaired by suturing during surgery. There was no esophageal fistula, conversion to an open operation or perioperative death in this series. The median length of hospital stay was 8 (6, 9) d. In all patients, the Stooler and Eckardt scores of postoperative 1, 6 and 12 months decreased compared to those of pre-operation (P<0.001). Conclusion RAHM-Dor is a safe and feasible avenue for the treatment of achalasia of cardia, and can achieve a satisfying short-term results. The learning curve shows a transition to the standard stage from the learning stage after 16-18 operations.
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Objective:To evaluate the effectiveness of pigtail catheter applying in single port video assistant thoracic surgery(VATS) for pulmonary tumor.Methods:A total of 441 patients undergoing single port VATS were obtained in this study. The patients were divided into chest-tube group and pigtail-catheter group. We used propensity score matching to match the patients 1∶1 and the clinical factors of the two groups were compared.Results:There were 143 patients in each group successfully matched by propensity score matching. The total drainage of 3 days after operation of pigtail-catheter group was significantly more than chest-tube group(375.49 ml vs. 285.03 ml, P<0.001). The pleural effusion on CT scan two weeks after surgery of pigtail-catheter group was significantly less than chest-tube group(131.77 ml vs. 178.84 ml, P=0.032). There was no significant difference between the two groups for the pain score, drainage days and inpatient days. Conclusion:Pigtail catheter can effectively improve the drainage of single port VATS, and there was no influence for the advantage of the surgery.
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Objective:To investigate the impact of the interaction between triglyceride-glucose(TyG)and obesity-related anthropometric indices on hypertension risk.Methods:A total of 3 356 permanent residents over 40 years were recruited from Songnan community, Baoshan district, Shanghai. All participants underwent questionnaire surveys, physical examinations, and biochemical parameter tests. TyG-WHR, TyG-WHtR, and TyG-BMI were obtained by multiplying TyG index with waist-to-hip ratio(WHR), waist-to-height ratio(WHtR), and body mass index(BMI), respectively. Logistic regression models were used to investigate the associations of the three indices and hypertension. The interactions of TyG index and obesity-related anthropometric indices on the risk of hypertension were analyzed in different genders.Results:After multivariable adjustment, the fourth quartile of TyG, TyG-WHR, TyG-WHtR, and TyG-BMI demostrated higher risk of hypertension compared with the first quantile, with OR(95% CI)2.93(2.37-3.62), 3.22(2.59-4.01), 4.33(3.46-5.42), and 4.07(3.27-5.06). Two abdominal obesity-related indicators WHR(RERI=1.52, 95% CI 0.12-2.92; AP=0.32, 95% CI 0.06-0.59)and WHtR(RERI=2.41, 95% CI 0.64-4.19; AP=0.39, 95% CI 0.15-0.63; SI=1.88, 95% CI 1.10-3.21)had a biological interaction with TyG index on the risk of hypertension in female, but not in male. Conclusion:The combination of TyG and obesity-related indicators is significantly correlated with the increased risk of hypertension, which may be influenced by gender and fat distribution type.
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Objective:To evaluate the effect of rat cardiac fibroblasts (RCF) on the expression of connexin43 (Cx43) in H9c2 cells during hypothermic hypoxia/reoxygenation.Methods:H9c2 cells cultured in vitro were divided into 4 groups ( n=12 each) using the random number table method: control group (group C), hypothermic hypoxia/reoxygenation group (group HHR), RCF co-culture group (group Co) and RCF co-culture plus hypothermic hypoxia/reoxygenation group (group Co+ HHR). Group C was incubated at 37℃ in 5% CO 2 + 95% air for 5 h. Group HHR was incubated at 4 ℃ in 5% CO 2 + 95% N 2 for 1 h and then at 37 ℃ in 5% CO 2 + 95% air for 4 h. In group Co and group Co+ HHR, H9c2 cells 0.3×10 5 cells/well were inoculated in the lower chamber and RCF 0.6×10 5 cells/well in the the upper chamber of a transwell ? culture dish.Group Co was incubated at 37 ℃ in 5% CO 2 + 95% air for 5 h. Group Co+ HHR was incubated at 4℃ in 95% N 2 + 5% CO 2 for 1 h, and then incubated at 37 ℃ in 5% CO 2 + 95% air for 4 h. The mortality rate of H9c2 cells was measured by trypan blue staining, the expression of Cx43 and extracellular signal-regulated protein kinases 1/2 (ERK1/2) by immunofluorescence, and the expression of Cx43, phosphorylated Cx43, ERK1/2 and phosphorylated ERK1/2 by Western blot. Results:Compared with group C, the mortality rate of H9c2 cells was significantly increased, the expression and phosphorylation of Cx43 were decreased, and the expression and phosphorylation of ERK1/2 were increased in group HHR ( P<0.05), and no significant change was found in the mortality rate of H9c2 cells or expression and phosphorylation of Cx43 and ERK1/2 in group Co ( P>0.05). Compared with group Co, the mortality rate of H9c2 cells was significantly increased, and the expression and phosphorylation of Cx43 and ERK1/2 were decreased in group Co+ HHR ( P<0.05). Compared with group HHR, the mortality rate of H9c2 cells was significantly increased, and the expression and phosphorylation of Cx43 and ERK1/2 were decreased in group Co+ HHR ( P<0.05). Conclusions:RCFs can decrease the expression and activity of Cx43 in H9c2 cells during hypothermic hypoxia/reoxygenation, and the mechanism may be related to the down-regulation of ERK1/2 expression and inhibition of ERK1/2 activity.
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OBJECTIVE@#To identify new biomarkers and molecular pathogenesis of Down syndrome (DS) by analyzing differentially expressed miRNAs in the placentas and their biological pathways.@*METHODS@#Whole transcriptome sequencing was used to identify the differentially expressed miRNAs in DS (n=3) and normal placental samples (n=3) diagnosed by prenatal diagnosis. The target genes were predicted using miRWalk, Targetscan and miRDB, and GO and KEGG pathway analyses were performed for gene enrichment studies.@*RESULTS@#We identified a total of 82 differentially expressed miRNAs in the placental tissues of DS, including 29 up-regulated miRNAs (fold change ≥2, P < 0.05) and 15 down-regulated miRNAs (fold change ≥2, P < 0.05), among which 10 miRNAs with relatively high expression abundance were selected for further analysis, including 4 up-regulated and 6 down-regulated miRNAs. These selected miRNAs shared the common target genes BTBD3 and AUTS2, both of which were associated with neurodevelopment. GO analysis showed that the target genes of the selected miRNAs were mainly enriched in protein binding, hydrolytic enzymes, metal ion binding protein combining, transferase activity, nucleotide, cytoplasmic constituents, nucleus composition, transcriptional regulation, RNA metabolism regulation, DNA-dependent RNA polymerase Ⅱ promoter transcriptional regulation, eye development, and sensory organ development. KEGG enrichment analysis showed that the target genes of these differentially expressed miRNAs were involved in the signaling pathways including tumor-related signaling pathway, PI3K-Akt signaling pathway, Ras signaling pathway, Rap1 signaling pathway, cytoskeletal regulatory signaling pathway, purine metabolization-related signaling pathway and P53 signaling pathway.@*CONCLUSION@#The differentially expressed miRNAs may play important roles in placental damage and pregnancy pathology in DS and provide clues for the prevention and treatment of mental retardation-related diseases.
Subject(s)
Female , Humans , Pregnancy , Cytoskeletal Proteins/metabolism , Down Syndrome/metabolism , Gene Expression Profiling , MicroRNAs/metabolism , Nerve Tissue Proteins , Phosphatidylinositol 3-Kinases/metabolism , Placenta/metabolism , Transcription Factors/metabolism , Transcriptome , Exome SequencingABSTRACT
Objective:To explore the ability of the Hammersmith Infant Neurological Examination (HINE) to predict the gross motor development of high-risk infants.Methods:A total of 207 high-risk infants were assessed with the HINE and the Gesell Developmental Schedule (GDS) at the ages of 3, 6, 9 and 12 months. They were then divided into a normal development group and a delayed group according to their gross motor development at 12 months old. The validity of the HINE′s discrimination was quantified retrospectively as the difference in the total HINE score at each follow-up month between the two groups. Spearman coefficients relating the total HINE score with the gross motor development quotient from the GDS were calculated at each follow-up month. The HINE′s total score threshold for predicting gross motor retardation at 12 months was determined from a receiver operating characteristics curve, and the predictive validity, sensitivity and specificity were evaluated by calculating the area under the curve.Results:At each time point the average total HINE score of the delayed group was significantly lower than the normal group′s average. The correlation between the HINE total scores and the GDS gross motor development quotients was strongest at 6 months old, and weakest at 3 months. The threshold total HINE score for predicting gross motor retardation at 12 months old was 60 at 3 months, 67 at 6 months, and then 71. The instrument′s sensitivity and specificity were very good at all four time points.Conclusion:The HINE can usefully predict gross motor retardation in the first year of life for high-risk infants. The critical value of the total score can be used as an auxiliary diagnostic reference for neuromotor development in such infants.
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OBJECTIVE@#To compare therapeutic effects of internal fixation with volar locking plate in treating extension and flexion type of distal radius fracture (DRF).@*METHODS@#From January 2015 to June 2018, 103 patients with DRF were retrospectively analyzed. According to original fracture displacement direction, patients were divided into extension fracture(Colles) group and flexion fracture (Smith) group. In Colles fracture group, there were 24 males and 44 females aged from 20 to 79 years old with an average of (59.0±13.4) years old;according to AO classification, 9 patients of type A2, 13 patients of type A3, 16 patientsof type C1, 17 patients of type C2 and 13 patients of type C3;the time from injury to operation ranged from 2 to 9 days with an average of (3.9±0.8) days. In Smith fracture group, there were 15 males and 20 females, aged from 27 to 87 years old with an average of (60.1±15.3) years old;according to AO classification, 4 patienst of A2, 7 patients of A3, 14 patients of C1, 5 patients of C2 and 5 patients of C3;the time from injury to operation ranged from 2 to 6 days with an average of (4.1±0.9) days. Operation time, fracture healing time and postoperative complications were recorded between two groups. Disabilities of arm, shoulder and hand (DASH) score at 6 and 8 weeks, 6 and 8 months were used to evaluate functional recovery of affected limbs during each follow up. Volar tilt, radial inclination and radius height were measured at 8 months after operation. Mayo score was measured at 8 months after operation to evaluate recovery of limb function.@*RESULTS@#All patients were followed up for 8 to 30 months with an average of (14.8±4.3) months, and no difference in follow up between two groups (@*CONCLUSION@#Patients with Colles fracture and Smith fracture could receive good reduction and fixation through volar locking plate. The radiographic parameters of both groups recovered satisfactorily after operation. Recovery of volar tilt of Smith fracture group is better than that of Colles fracture group, and early recovery function of Colles fracture group is better than that of Smith group, but there is no significant difference in long-term wrist joint function and incidence of postoperative complications between two groups.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Bone Plates , Fracture Fixation, Internal , Radius Fractures/surgery , Range of Motion, Articular , Retrospective Studies , Treatment Outcome , Wrist JointABSTRACT
Objective:To investigate the safety and effectiveness of extracorporeal membrane oxygenation (ECMO) in emergency treatment of critically ill pregnant women.Methods:Clinical data of 8 pregnant women with severe cardiopulmonary dysfunction during the perinatal period treated by ECMO in the department of intensive care unit (ICU) of Nanjing Drum Tower Hospital, the Affiliated Hospital to Nanjing University Medical School from September 2017 to November 2020 were retrospectively analyzed. Results:For the 8 pregnant women, the mean age was (32.5±6.3) years old. Body weight was (73.5±8.1) kg. Gestational age was (31.0±4.4) weeks. Acute physiology and chronic health evaluationⅡ (APACHEⅡ) score was 13.0±6.6, and sequential organ failure assessment (SOFA) score was 8.3±3.8. Among them, 5 pregnant women suffered from severe pneumonia and were treated with veno-venous ECMO (VV-ECMO). Another 3 pregnant women with heart failure underwent veno-arterial ECMO (VA-ECMO). The initial ECMO flow rate was set to 2.0-3.0 L/min. Then the highest flow rate was (3.1±0.6) L/min, and the average ECMO running time was (174±36) hours. The length of ICU stay was (16.0±5.4) days. Six pregnant women (5 with severe pneumonia and 1 with peripartum cardiomyopathy) successfully evacuated from ECMO and survived. Two pregnant women with pulmonary hypertension showed poor prognosis. In total, seven babies survived. Two of them were delivered after ECMO evacution, and one underwent emergency cesarean section with ECMO support. In another case, the fetus could not be delivered due to under-gestational weeks. During this period, there were no serious bleeding complications. One pregnant woman developed heparin-induced thrombocytopenia and thrombosis (HITT), then she received another anticoagulant treatment. One pregnant woman got sequential anticoagulation therapy for 3 months on account of thrombosis in the puncture vessel.Conclusions:ECMO has played an active role in the rescue of critically ill pregnant women. For those with reversible severe cardiopulmonary dysfunction, it is necessary to evaluate the application of ECMO as early as possible to improve the survival rate of mothers and infants.
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Clinical data of a child diagnosed as Gillespie syndrome in the Department of Rehabilitation, Children′s Hospital of Nanjing Medical University in November 2019 were retrospectively analyzed.The 6-month-old boy presented psychomotor retardation, muscular hypotonia, photophobia, nystagmus and inability to focus and follow objects.Slit lamp examination of eyes revealed fixed dilation pupils, bilateral partial aniridia and characteristic iris strands.Genome sequencing and bioinformatics analysis showed a heterozygous splicing mutation in intron 26 of ITPR1 gene, c.3256-1G>A, which was a newly identified pathogenic mutation that was not been reported yet.Moreover, pa-rents of this case did not carry this mutation.It is suggested that Gillespie syndrome should be considered in children with bilateral partial aniridia, psychomotor retardation and muscular hypotonia.Genetic sequencing is helpful for early diagnosis.
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Objective:To identify 24 <italic>Rana</italic> species such as <italic>Rana dybowskii</italic> by mitochondrial cytochrome C oxidase subunit I （<italic>CO</italic>Ⅰ） gene-based DNA barcoding and build the neighbour-joining （NJ） tree for hierarchical cluster analysis， so as to provide a basis for the identification and classification of <italic>Rana</italic> species as well as the discovery of new species. Method:<italic>R. dybowskii</italic>， <italic>R. chensinensis</italic>， <italic>R. amurensis</italic>， <italic>R. culaiensi</italic>s， and <italic>R. huanrenesis</italic>， ten for each species， were collected for DNA extraction and polymerase chain reaction （PCR） amplification<italic> </italic>and sequencing. A total of 50 <italic>CO</italic>Ⅰ gene sequences were obtained. Then 163 <italic>CO</italic>Ⅰ gene sequences for 24 species of <italic>Rana</italic> and one <italic>CO</italic>Ⅰ gene sequence for <italic>Pelophylax</italic>，<italic> Odorrana</italic>， <italic>Nidirana</italic>， <italic>Hylarana</italic>， and <italic>Amolops</italic> were harvested from GenBank. After sequence alignment by MEGA X， the parsimony-informative sites of <italic>CO</italic>Ⅰ gene sequences were analyzed and the intraspecific and interspecific genetic distances were calculated， followed by the built of NJ tree and hierarchical cluster analysis. Result:The <italic>CO</italic>Ⅰ gene sequences of 24<italic> Rana</italic> species including <italic>R. dybowskii</italic> were 554 bp in length and there were 210 parsimony-informative sites in total. The intraspecific genetic distance of each species was smaller than 2%. Except that the interspecific genetic distance between <italic>R. sangzhiensis</italic> and <italic>R. zhengi</italic> was 0.004， the genetic distances between the other species ranged from 0.024 to 0.228. <italic>R. sangzhiensis</italic> and <italic>R. zhengi</italic> were clustered into one branch and some <italic>R. dybowskii</italic> and <italic>R. uenoi</italic> into one branch. There were two separate branches for <italic>R. chensinensis</italic> and the other species were all clustered independently. Conclusion:<italic>CO</italic>Ⅰ-based DNA barcoding enabled the identification of 24 species of <italic>Rana</italic> including <italic>R.dybowskii</italic>. The findings supported that <italic>R. sangzhiensis</italic>， <italic>R. zhengi</italic>， <italic>R. coreana</italic>， and <italic>R. kunyuensis</italic> were the same species. One branch of <italic>R. chensinensis </italic>might be one of the four undownloaded species in Ranidae or a new species. The results have demonstrated that <italic>CO</italic>Ⅰ-based DNA barcoding allows not only the identification of 24 species of Rana including <italic>R. dybowskii </italic>but also the classification of ranidae species and the discovery of new species or subspecies.
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OBJECTIVE：To prelimi narily investigate the possible mechanism of orazamide to prevent anti-tuberculosis drug-induced liver injury （ATB-DILI）. METHODS ：A total of 60 Kunming mice were randomly divided into blank group ，model group，positive control group [diammonium glycyrrhizinate 60 mg/（kg·d）]，orazamide low-dose ，medium-dose and high-dose groups [ 80，160，320 mg/（kg·d）]，with 10 mice in each group. Except for blank group ，other groups were given isoniazid [ 75 mg/（kg·d）]+rifampicin [ 75 mg/（kg·d）] for 14 days intragastrically to induce ATB-DILI model. At the same time ，administration groups were given relevant medicine intragastrically ，blank group and model group were given normal saline intragastrically. The administration volume was 20 mL/（kg·d），once a day ，for consecutive 14 days. The general conditions of the mice were observed and recorded every day ，such as growth and development ，mental and diet state. After last medication ，liver index was calculated ， and HE staining was adopted to observe pathological changes of liver tissue of mice. The positive expression of high mobility group protein B 1 （HMGB1） and NF-κ B in liver tissue were detected by streptavidin biotin-peroxidase complex （SABC） immuno- histochemistry. The serum levels of liver function indexes in serum ，the protein expression of advanced glycation end product receptor（RAGE）and TNF-α in liver tissue were detected by ELISA. RESULTS：Compared with blank group ，the growth and development of mice in the model group were slow ，and their appetite and spirit were poor. The liver index ，serum levels of TBIL ， DBIL，ALT，AST，ALP，TBA and γ-GT were increased significantly （P＜0.05）. Structural disorder of liver lobules ，degeneration and necrosis of liver cells and inflammatory cell infiltration were observed. The expression of HMGB 1，NF-κB，RAGE and TNF-α in liver tissue were elevated significantly （P＜0.05）. Compared with model group ，the general condition of mice were all improved to different extents in orazamide low-dose ，medium-dose and high-dose groups ，positive control group ，while liver index and above serum indexes were all decreased significantly （P＜0.05）. The pathological changes of liver tissue were all improved to different extents ，while the protein expression of HMGB 1，NF-κB，RAGE and TNF-α were all decreased significantly（P＜0.05）. The improvement of above indexes in orazamide high-dose group were all significantly better than orazamide low-dose and medium-dose groups （P＜0.05）；the levels of ALP and TBA in orazamide high-dose group were significantly lower than positive control group （P＜0.05）. CONCLUSIONS ：Orazamide can prevent ATB-DILI induced by isoniazid combined with rifampicin in mice，the mechanism of which may be associated with down-regulating the protein expression of HMGB 1 and RAGE in liver tissue and inhibiting the secretion of inflammatory factors.
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OBJECTIVE@#To explore the clinical features and genetic characteristics of a child with 5q14.3 microdeletion syndrome.@*METHODS@#Whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs). Candidate CNVs were verified by real-time fluorescence quantitative PCR.@*RESULTS@#The patient presented with psychomotor retardation, epilepsy, peculiar face and hypotonia. The results of WES suggested that he has carried a heterozygous deletion for chr5:86 564 268-88 119 605. CNV-seq indicated that the patient carried a heterozygous deletion of 4.76 Mb heterozygous deletion on chromosome 5q14.3. The MEF2C gene and RASA1 gene in the deletion area were verified by real-time fluorescence quantitative PCR. The results showed that the MEF2C geneand RASA1 gene were heterozygous deletion, which was consistent with the sequencing results.@*CONCLUSION@#The child was diagnosed with 5q14.3 microdeletion syndrome. Haploinsufficiency of the MEF2C gene may underlie the manifestations of 5q14.3 microdeletion syndrome.
Subject(s)
Humans , Male , Chromosome Deletion , Chromosome Disorders , DNA Copy Number Variations , Genetic Testing , Phenotype , Exome Sequencing , p120 GTPase Activating ProteinABSTRACT
OBJECTIVE@#To investigate the effects of ALKBH5 on migration, invasion and epithelial-mesenchymal transition (EMT) of human trophoblast cells.@*METHODS@#The expression plasmid of ALKBH5 or a negative control plasmid (ALKBH5-NC) was transfected in human trophoblast HTR-8 /SVneo cells, and the expressions of ALKBH5 mRNA and protein were detected by qRT-PCR and Western blotting. Transwell assay was used to assess the changes in migration and invasion abilities of the trophoblast cells after the transfection. Western blotting was performed to detect the expressions of EMT-related proteins in the cells including vimentin, fibronectin, E-cadherin, N-cadherin, MMP9 and MMP2.@*RESULTS@#ALKBH5 mRNA and protein expressions were significantly higher in ALKBH5 group than in the control group (@*CONCLUSIONS@#ALKBH5 is involved in the pathogenesis of preeclampsia by inhibiting EMT of trophoblast cells and hence reducing their migration and invasion abilities.
Subject(s)
Female , Humans , Pregnancy , AlkB Homolog 5, RNA Demethylase , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition , Pre-Eclampsia , Trophoblasts , Vimentin/geneticsABSTRACT
BACKGROUND@#Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people.@*METHODS@#A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations.@*RESULTS@#There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = -0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age.@*CONCLUSIONS@#Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.
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Objective:To explore the application effect of standardized patient (SP) combined with structured feedback framework method in the training of diagnostic inquiry.Methods:A total of 338 students in Grade 2016 of Tianjin Medical University majored clinical medicine was divided into experimental group and control group. Both groups were applied with routine teaching method. The experimental group were trained by SP combined with structured feedback framework method in diagnostic inquiry. Students in the two groups were evaluated systematically by examination of inquiry skills, and the satisfaction with SP was investigated. SPSS 21.0 was used for t test, and Wilcoxon symbolic rank test and chi-square test were performed in the study. Results:After trained by SP combined with structured feedback framework method, the experiment group got better performance in inquiry skill examinations, including total points [85.750 (80.875, 89.000), P<0.001], history of present illness [38.000 (33.000, 42.000), P=0.022], history of past illness history [4.000 (4.000, 5.000), P=0.008] and personal history [2.000 (1.000, 4.000), P<0.001], as well as the ability of collecting the history [9.000 (9.000, 10.000), P=0.002]. Moreover, students in the experimental group were more satisfied with SP than those in the control group ( P=0.000). Conclusion:The SP combined with structured feedback framework method is applicable in the training of diagnostic inquiry, and it’s worth promoting in practice.
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Objective:To determine the changes in the expression of myocardial miRNA and the target genes in the rats with hypothermic ischemia-reperfusion (I/R) arrhythmia.Methods:Clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 300-400 g, were anesthetized, the chest was opened, and the heart was taken to establish an isolated heart perfusion model.Six successfully perfused isolated hearts were divided into 2 groups ( n=3 each) using a random number table method: control group (group C) and heart I/R group (IR group). The model of hypothermic global I/R injury was established by interrupting perfusion for 60-min followed by 30-min reperfusion in chloral hydrate-anesthetized rats.The arrhythmia score was recorded during reperfusion.High-throughput sequencing was used to identify the differentially expressed miRNAs in two groups.The RNAhybrid and miRanda databases were used to predict the target genes of mRNA regulated by the differentially expressed miRNAs, and the enrichment for target genes was performed by Gene Ontology and KEGG databases, and the miRNAs closely related to arrhythmia and with higher expression were selected to carry out the real-time polymerase chain reaction detection. Results:The results of high-throughput sequencing showed that there were 7 differentially expressed miRNAs (novel-miR-17, novel-miR-19, novel-miR-30, novel-miR-43, rno-miR-122-5p, novel-miR-16 and rno-miR-429) in group IR as compared with group C. There were 4 miRNAs that were closely related to arrhythmia and had higher expression: the expression of novel-miR-17, novel-miR-30 and rno-miR-122-5p was significantly up-regulated, and the expression of rno-miR-429 was down-regulated in group IR when compared with group C ( P<0.05). The miRNA-mRNA correlation analysis revealed that GJA1 gene was the target of novel-miR-17. Conclusion:Myocardial novel-miR-17 is involved in the occurrence of hypothermic I/R arrhythmia probably by acting on GJA1 gene in rats.
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Objective:To evaluate the effect of electroacupuncture (EA) on electrophysiological characteristics of ventricular myocardium during myocardial ischemia-reperfusion (I/R) in rats.Methods:Twenty-four clean-grade healthy adult male Sprague-Dawley rats, weighing 280-320 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (group SH), I/R group and group EA.The model of myocardial I/R injury was established by ligating the left anterior descending branch of coronary artery for 30 min followed by 30-min reperfusion in anesthetized rats.Bilateral Neiguan acupoints in forelimbs were stimulated for 30 min during the period of reperfusion in group EA.Heart rate (HR), monophasic action potential amplitude (MAPA), maximum depolarization rate (V max), and monophasic action potential duration at 90% repolarization (MAPD 90) were recorded.The development of arrhythmias and arrhythmias score were recorded during reperfusion. Results:Compared with group SH, HR was significantly decreased, MAPA and V max were decreased, MAPD 90 was prolonged, and the incidence of ventricular premature beat, ventricular tachycardia and ventricular fibrillation and arrhythmias score were increased at T 1, 2 in I/R and EA groups ( P<0.05). Compared with group I/R, HR was significantly increased, MAPA and V max were increased, MAPD 90 was shortened, and the incidence of ventricular tachycardia and ventricular fibrillation and arrhythmias score were decreased at T 2 in EA group ( P<0.05). Conclusion:EA can accelerate myocardial depolarization and shorten repolarization, thus decreasing the occurrence of reperfusion arrhythmia in rats.