Objective To explore the relevant factors of new-onset conduction disturbance(NOCD)after transcatheter aortic valve replacement(TAVR),such as anatomical structure,device type,surgical strategies,etc.,discover relevant predictive factors,and establish a predictive model to assess the risk of conduction blockages.Methods From January 2016 to March 2022,clinical data of symptomatic patients with severe aortic valve stenosis or severe regurgitation who underwent TAVR at Xiangya Second Hospital of Central South University were collected through the hospital information system and imaging database.ECG,echocardiography,CTA,surgical materials,etc.,were extracted and analyzed by specialists.SPSS software was used for statistical analysis,and a multi-factor regression prediction model for NOCDwas built.Results A total of 184 patients were included,the occurrence rate of NOCD after TAVR was 31.0%,pure regurgitation patients'NOCD occurrence rate was 63.6%(7/11).The NOCD group had a larger aortic angles[(57.7±10.3)°vs.(52.0±9.0)°,P＜0.001],larger Oversizing[(129±28)%vs.(120±21)%,P=0.018],deeper implantation depth[(7.2±5.1)mm vs.(4.8±4.2)mm,P=0.001],and higher pure regurgitation patients'proportion[12.3%vs.3.1%,P=0.037]than the non-NOCD group.Multifactorial Logistic regression analysis indicated that an aorta angle＞54.5°(OR 3.78,95%CI 1.86-7.63,P＜0.001)or implantation depth＞5.7 mm(OR 3.39,95%CI 1.68-6.85,P＜0.001)are independent risk factors for new onset conduction disturbances after TAVR,and a predictive model was established with aortic angle,implantation depth,and Oversizing ratio as variables.The receiver operating characteristics curve showed area under ROC curve 0.709,95%CI 0.623-0.795,predicting NOCD after TAVR.Conclusions A retrospective analysis carried out at a single center discovered that the aortic angle in the NOCD group was larger than that in the non-NOCD group,the Oversizing ratio was higher,the implantation location was deeper,and there was a higher proportion of patients with pure regurgitation lesions.An aortic angle greater than 54.5°or an implantation depth more than 5.7 mm were identified as independent risk factors for NOCD after TAVR.

Humans ; Cyclin D1 ; Melanoma ; Skin Neoplasms ; Cyclin-Dependent Kinase 4

Objective: To compare the differences in clinical symptoms and the time required for diagnosis of benign paroxysmal positional vertigo (BPPV) between older patients and young and middle-aged patients in the structured inquiry of dizziness history. Methods: The medical records of 6 807 patients diagnosed with BPPV from the Vertigo Database of Vertigo Clinical Diagnosis, Treatment, and Research Center of Beijing Tiantan Hospital, Capital Medical University, between January 2019 and October 2021 were retrospectively analyzed. The data included basic demographic information, clinical symptoms in a structured medical history questionnaire, and the time interval from the appearance of BPPV symptoms to diagnosis consultation. The patients were divided into the young and middle-aged group (<65 years old) and the older group (≥65 years old). The differences in clinical symptoms and consultation time were compared between these two groups. Categorical variables were represented by numbers (%), and compared using Chi-squared tests or Fisher's exact probability test for analysis; whereas, continuous variables conforming to normal distribution were represented by mean±standard deviation. Both data groups were compared and analyzed by Student's t-test. Results: The mean age of the older group was 65-92 (71±5) years, while the mean age of the middle-aged group was 18-64 (49±12) years. The incidence of vertigo (42.5% vs. 49.1%, χ²=23.69, P<0.001); vertigo triggered by changes in position of the head or body (52.4% vs. 58.7%, χ²=22.31, P<0.001); and autonomic symptoms (10.1% vs. 12.4%, χ²=7.09, P=0.008) were lower, but hearing loss (11.8% vs. 7.8%, χ²=27.36, P<0.001) and sleep disorders (18.5% vs. 15.2%, χ²=11.13, P=0.001) were higher in the older group than in the young and middle-aged group. The time from the appearance of dizziness to diagnosis was commonly longer in the older patient group than the other group (55.0% vs. 38.5%, χ²=55.95, P<0.001). Conclusions: Older patients with BPPV have more atypical symptoms and complex concomitant symptoms than young and middle-aged patients. For older patients with dizziness, positional testing is needed to confirm the possibility of BPPV even if the clinical symptoms are atypical.
Middle Aged ; Humans ; Aged ; Aged, 80 and over ; Adolescent ; Young Adult ; Adult ; Benign Paroxysmal Positional Vertigo/therapy* ; Dizziness/diagnosis* ; Retrospective Studies ; Patients ; Surveys and Questionnaires

Objective: To investigate the causes and management of long-term persistent pelvic presacral space infection. Methods: Clinical data of 10 patients with persistent presacral infection admitted to the Cancer Hospital of Zhengzhou University from October 2015 to October 2020 were collected. Different surgical approaches were used to treat the presacral infection according to the patients' initial surgical procedures. Results: Among the 10 patients, there were 2 cases of presacral recurrent infection due to rectal leak after radiotherapy for cervical cancer, 3 cases of presacral recurrent infection due to rectal leak after radiotherapy for rectal cancer Dixons, and 5 cases of presacral recurrent infection of sinus tract after adjuvant radiotherapy for rectal cancer Miles. Of the 5 patients with leaky bowel, 4 had complete resection of the ruptured nonfunctional bowel and complete debridement of the presacral infection using an anterior transverse sacral incision with a large tipped omentum filling the presacral space; 1 had continuous drainage of the anal canal and complete debridement of the presacral infection using an anterior transverse sacral incision. 5 post-Miles patients all had debridement of the presacral infection using an anterior transverse sacral incision combined with an abdominal incision. The nine patients with healed presacral infection recovered from surgery in 26 to 210 days, with a median time of 55 days. Conclusions: Anterior sacral infections in patients with leaky gut are caused by residual bowel secretion of intestinal fluid into the anterior sacral space, and in post-Miles patients by residual anterior sacral foreign bodies. An anterior sacral caudal transverse arc incision combined with an abdominal incision is an effective surgical approach for complete debridement of anterior sacral recalcitrant infections.
Humans ; Reinfection ; Rectum/surgery* ; Rectal Neoplasms/surgery* ; Drainage ; Anal Canal/surgery* ; Pelvic Infection

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.
Animals ; Bile Acids and Salts ; Cholestasis/drug therapy* ; Chromatography, Liquid ; Medicine, Tibetan Traditional ; Metabolomics ; Mice

Objective:To establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for plasma caffeine concentration detection, and to explore the clinical value of caffeine therapeutic drug monitoring (TDM) in the treatment of premature infants with respiratory distress syndrome (RDS).Method:Take the plasma sample in a centrifuge tube, add the caffeine deuterated isotope internal standard, then add the protein precipitant, vortex the mixture thoroughly, and centrifuge the supernatant to enter the mass spectrometry analysis. The mobile phase were methanol and water, gradient elution; the column temperature was 45 ℃, the method was established using Shimadzu LC-30AD-CL liquid system and AB SCIEX 4500 QTRAP mass spectrometer, and the sensitivity, specificity, linearity, accuracy imprecision, matrix effect, and carry-over of the method were evaluated. Sample from 30 patients diagnosed with neonatal RSD were collected in the Department of Neonatology of Renmin Hospital of Wuhan University from February to April 2021, then detected the trough concentration of caffeine in premature infants with RDS after taking the same dose of caffeine to assess the impact of individual variation on caffeine drug concentration.Results:The detection limit of caffeine was 0.02 μg/ml, and the lowest limit of quantification was 0.05 μg/ml. It showed good linearity ( R2=0.9986, R>0.99) in the concentration range from 1.0 to 100.0 μg/ml, specificity (recovery rate of 85.52%-114.12%), accuracy (recovery rate 85.97%-114.53%), intra-day and inter-day imprecision ( CV 6.01%-11.28%), matrix effects and carryover pollution were negligible. The trough concentration of 30 preterm infants with RSD after taking the same dose of caffeine (10 mg/kg) was (25.45±11.61) μg/ml, and the coefficient of variation was 44.88%. Conclusion:This study established an accurate and reliable UPLC-MS/MS method with low sample consumption to monitor the blood concentration of caffeine; caffeine TDM has certain clinical application value, which can be used to assist RDS diagnosis and treatment and improve the efficacy of caffeine.

OBJECTIVE: To evaluate the necessity and suitability of the anti-HCV ELISA teot gray zone setted up by 7 blood station laboratories. METHODS: 7 blood station laboratories were coded as 1, 2, 3, 4, 5, 6 and 7 respectively; 8 kinds of ELISA reagents were coded as A, B, C, D, E, F, G and H respectively. 1 or 2 of 8 ELISA reagents produced by different manufactories were used to detect the anti-HCV in specimens of same group by 7 blood station laboratories; the Westen blot was used to detect the specimens with difference of detected results so as to difine the serological status of specimens. The true positive rate of specimens detected by laboratories and gray zone-comfirined positive rate of specimens were accounted so as to analyze the necessity of setting up the gray zone for anti-HCV ELISA test of 7 blood station laboratories; the optimal cut-off value for anti-HCV ELISA test was determined in 7 blood station laborafories by ROC curve and the changes of sensitivity and specificity of 3 different cut-off value(laboratory work cut-off value, manifactory-recommended cun-off value and optimal cut-off value) were compared so as to analyze the suitability of gray zone for anti-HCV ELISA test in 7 blood station laboratories. RESULTS: The true positive rate detected by 7 blood station laboratories, out of which coded 1 laboratory used 2 kinds of coded A, B reagents was 95.40%(1A), 99.23% (1B), 94.25% (2C), 96.17% (3D), 98.08% (4E), 96.93% (5F), 97.32%(6G) and 93.10%(7H). Except for 2C(94.25%) and 7H(93.10%), the true positive rate detected by laboratoies which not sutted up gray zone, the gray zone-con-firmed positive rate in 6 blood station laboratories setted up gray zone: was 0.00%, 0.00%, 21.43%, 0.00%, 0.00%, 0.00% and 38.89%. The comparison of 3 different cut-off valuces by ROC curve showed that the anti-HCV cut-off values in 5 laboratories(1B, 2C, 4E, 5F and 6G) were as follows: optimal cut-off value＞manufactory recommeded cut-off value＞laboratory work cut-off value, thus use of manufactory-recommeded cut-off value abreadly has reached the high sensitivity requinements for laboratory screening; however, the optimal cut-off value in laboratories 1A, 3B and 7H, thas the appropriate gray zone should be used. In 6 laboratories setting up gray zone, the gensitivity in 3D, 7H laboratories only a little improved (1.60% and 2.70% raspectively) in Eamparison between laboratory work cut-off value and manufactorg-recommeded cut-off value; moreover, the sensitivity in other laboratories not is changed, but the specificity decreased (0.20%-0.50%). CONCLUSION In addition to setting up the appropriate gray zone in laboratories 1A, 3D and 5H, the gray zone in other laboratories may be cancelled. Even in the same laboratory, the setting up the gray zone also should be scientifically assessed, the same scale cannot be blindly used, thus appropniate strategies should be established.
Enzyme-Linked Immunosorbent Assay ; Hepatitis C ; Hepatitis C Antibodies ; Humans ; ROC Curve ; Sensitivity and Specificity

Objective To make a parallel mining the data of expression differences of a crucial gene XPA involved in nucleotide excision repair pathway of human skin microarrays by bioinformatics from the system level.Methods Using the ScanGEO, the data of microarrays which included the significant differences expression level of XPA were screened and analyzed from 59 human skin samples in the GEO database. Results There were 7 samples with the down-regulated expression of XPA: cutaneous malignant melanoma, epidermal injury model, DNA damage and UV radiation, foreskin fibroblast response to Toxoplasma gondii RH type 1 (ROP5) mutant infection, interleukin-20 subfamily cytokines effect on epidermal keratinocytes, Egr-1 overexpression effect on skin fibroblasts in vitro: time course, in vitro model for inflammatory dendritic cells.Present expression down. Conclusion Based on the GEO database and ScanGEO, high-throughput shared data can be screened and analyzed efficiently.

Objective To observe the effects of percutaneous endoscopic gastrostomy (PEG)on mortality and complications in patients with persistent dysphagia after stroke using a points scoring system for selecting PEG indication.Methods A total of 75 patients were divided into low score group without PEG,high score group without PEG and low score group with PEG (n=25 each).The follow-up period was 18 months,and the differences in complications,mortalities and survival periods among groups were compared.Results The number of times of aspiration pneumonia was (1.36± 1.44) in low score group,(1.96±2.28) in high score group,(0.36±0.64) in low score group with PEG,with statistically significant differences among three groups (H=7.148,P=0.028).No difference in the morbidity of aspiration pneumonia was found between low score group and high score group (P=0.189).The number of times of aspiration pneumonia was decreased in low score groups after PEG versus in low score group without PEG (P=0.030) and in high score group (P＜0.01).The numberof times of gastrointestinal hemorrhage was (0.48± 0.77)in low score group,(0.64± 0.91) in high score group,(0.12±0.33) in low score group with PEG,with statistically significant differences among three groups (H=5.532,P =0.063).No statistically significant difference in gastrointestinal hemorrhage was found between low score groups and low score group after PEG (P=0.430),as well as between low score group and low score group with PEG (P=0.079).The morbidity of gastrointestinal hemorrhage was lower in low score group than in high score group (P=0.012).The survival rate at the observation end was 88.0％ (22/25),52.0％ (13/25) and 92.0％ (23/25) in low score group,high score group and low score group with PEG,respectively,with statistically significant difference among the three groups (x2 =7.906,P =0.001).Kaplan-Meier survival curve showed that the survival period were longer in the low score group with or without PEG than in high score group (P＜0.01),but no statistically significant difference was found between low score groups with or without PEG (P=0.626).Conclusions The reasonable evaluation using a points-scoring system before PEG might predict the prognosis of such patients:the higher score would indicate higher mortality.PEG operation for low score group with better condition could decrease the aspiration pneumonia and decrease gastrointestinal hemorrhage significantly,but could not prolong general survival time and decrease general mortality.

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.
Action Potentials ; physiology ; Biomarkers ; metabolism ; Cell Culture Techniques ; Embryoid Bodies ; cytology ; metabolism ; Gene Expression ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Lateral Ventricles ; cytology ; growth & development ; metabolism ; Microcephaly ; genetics ; metabolism ; pathology ; Models, Biological ; Mutation ; Neocortex ; cytology ; growth & development ; metabolism ; Nerve Tissue Proteins ; deficiency ; genetics ; Neurogenesis ; genetics ; Neurons ; cytology ; metabolism ; Organoids ; cytology ; metabolism ; PAX6 Transcription Factor ; genetics ; metabolism ; Patch-Clamp Techniques ; SOXB1 Transcription Factors ; genetics ; metabolism ; Zonula Occludens-1 Protein ; genetics ; metabolism