Bioinformatic Analysis and Experimental Validation of Ubiquitin-Proteasomal System-Related Hub Genes as Novel Biomarkers for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a common progressive neurodegenerative disease. The Ubiquitin-Protease system (UPS), which plays important roles in maintaining protein homeostasis in eukaryotic cells, is involved in the development of AD. This study sought to identify differential UPS-related genes (UPGs) in AD patients by using bioinformatic methods, reveal potential biomarkers for early detection of AD, and investigate the association between the identified biomarkers and immune cell infiltration in AD. METHODS: The differentially expressed UPGs were screened with bioinformatics analyses using the Gene Expression Omnibus (GEO) database. A weighted gene co-expression network analysis (WGCNA) analysis was performed to explore the key gene modules associated with AD. A Single-sample Gene Set Enrichment Analysis (ssGSEA) analysis was peformed to explore the patterns of immune cells in the brain tissue of AD patients. Real-time quantitative PCR (RT-qPCR) was performed to examine the expression of hub genes in blood samples from healthy controls and AD patients. RESULTS: In this study, we identified four UPGs (USP3, HECW2, PSMB7, and UBE2V1) using multiple bioinformatic analyses. Furthermore, three UPGs (USP3, HECW2, PSMB7) that are strongly correlated with the clinical features of AD were used to construct risk score prediction markers to diagnose and predict the severity of AD. Subsequently, we analyzed the patterns of immune cells in the brain tissue of AD patients and the associations between immune cells and the three key UPGs. Finally, the risk score model was verified in several datasets of AD and showed good accuracy. CONCLUSIONS: Three key UPGs are identified as potential biomarker for AD patients. These genes may provide new targets for the early identification of AD patients.

PARP-1 inhibits DNMT1-mediated promoter methylation and promotes linc01132 expression in benzene-exposed workers and hydroquinone-induced malignant transformed cells.

Hydroquinone (HQ), one of the main active metabolites of benzene, can induce the abnormal expression of long non-coding RNA (lncRNA). Studies have shown that lncRNA plays an important role in the occurrence of hematologic tumors induced by benzene or HQ. However, the molecular mechanism remains to be elucidated. Here, we investigated the molecular mechanism by which poly(ADP-ribose)polymerase 1 (PARP-1) interacts with DNA methyltransferase 1 (DNMT1) to regulate promoter methylation mediated linc01132 expression in HQ-induced TK6 malignant transformed cells (HQ-MT). The results revealed that the expression of linc01132 was increased in benzene-exposed workers and HQ-MT cells. The methylation of linc01132 promoter region was inhibited. Furthermore, in HQ-MT cells treated with 5-Aza-2'-deoxycytidine (5-AzaC) (DNA methyltransferase inhibitor) or trichostatin A (TSA) (histone deacetylation inhibitor), the expression of linc01132 was increased due to the regulation of DNA promoter methylation level by inhibiting DNMT1 expression. The methylation level of linc01132 promoter was correlated negatively with the expression of linc01132 in benzene-exposed workers, indicating that DNA methylation may contribute the expression of linc01132. Knockout of DNMT1, not DNMT3b, increased the expression of linc01132 as well as the demethylation of linc01132 promoter in HQ-MT cells. It was found that by knockdown PARP-1, the expression of DNMT1 in the nucleus was increased by immunofluorescence confocal microscopy, leading to the inhibition of hypermethylation in the promoter region of linc01132. Therefore, PARP-1 inhibits DNA methyltransferase (DNMT)-mediated promoter methylation and plays a role in linc01132 expression in benzene-exposed workers or HQ-MT cells, and is associated with benzene or HQ induced leukemia progression.

Safety and feasibility of neoadjuvant chemotherapy as a surgical bridge for acute left-sided malignant colorectal obstruction: a retrospective study.

BACKGROUND: For colorectal cancer, preoperative (neoadjuvant) chemotherapy is more effective than postoperative chemotherapy because it not only eradicates micrometastases more effectively but also reduces the risk of incomplete intraoperative resection and tumor cell shedding. For the treatment of acute left-sided malignant colorectal obstruction, colorectal stents as well as stoma are being used to relieve the obstructive colorectal cancer, and as a bridge to surgery, allowing easy mobilization and resection of the colon. Neoadjuvant chemotherapy combined with self-expandable metal stents (SEMS) or neoadjuvant chemotherapy combined with decompressing stoma (DS) can be used as a bridge to elective surgery (BTS) as an alternative to emergency surgery in patients with acute left-sided malignant colorectal obstruction, but its benefit is uncertain. The purpose of this study was to evaluate the safety and feasibility of neoadjuvant chemotherapy as a bridge to surgery in the treatment of acute left-sided malignant colorectal obstruction. METHODS: Data from patients who were admitted with acute left-sided malignant colorectal obstruction between January 2012 and December 2020 were retrospectively reviewed, and patients with gastrointestinal perforation or peritonitis were excluded. We performed one-to-two propensity score matching to compare the stoma requirement, postoperative complications, and other short-term oncological outcomes between the neoadjuvant chemotherapy group and surgery group. RESULTS: There were no differences in intraoperative blood loss, operative time, one-year postoperative mortality, and postoperative tumor markers between the two groups. The 1-year recurrence-free survival (RFS) rates of neoadjuvant chemotherapy group and surgery group were 96.8 and 91.3% (p = 0.562). The neoadjuvant chemotherapy group was able to reduce stoma rate 1 year after surgery (p = 0.047). Besides, the neoadjuvant group significantly reduced postoperative bowel function time (p < 0.001), postoperative hospital stay (p < 0.001), total hospital stay (p = 0.002), postoperative complications (p = 0.017), reduction in need to stay in the intensive care unit (ICU) (p = 0.042). CONCLUSIONS: Neoadjuvant chemotherapy as a bridge to elective surgery in patients with acute left-sided malignant colorectal obstruction is safe and has many advantages. Prospective multicenter studies with large samples are needed to further evaluate the feasibility of neoadjuvant chemotherapy.

Analysis and evaluation of different sequencing depths from 5 to 20 million reads in shotgun metagenomic sequencing, with optimal minimum depth being recommended.

Our study was to analyze and evaluate the impact of different shotgun metagenomic sequencing depths from 5 to 20 million in metagenome-wide association studies (MWASs), and to determine the optimal minimum sequencing depth. We included a set of 200 previously published gut microbial shotgun metagenomic sequencing data on obesity (100 obese vs. 100 non-obese). The reads with original sequencing depths >20 million were downsized into seven experimental groups with depths from 5 to 20 million (interval 2.5 million). Using both integrated gene cluster (IGC) and metagenomic phylogenetic analysis 2 (MetaPhlAn2), we obtained and analyzed the read matching rates, gene count, species richness and abundance, diversity, and clinical biomarkers of the experimental groups with the original depth as the control group. An additional set of 100 published data from a colorectal cancer (CRC) study was included for validation (50 CRC vs. 50 CRC-free). Our results showed that more genes and species were identified following the increase in sequencing depths. When it reached 15 million or higher, the species richness became more stable with changing rate of 5% or lower, and the species composition more stable with ICC intraclass correlation coefficient (ICC) higher than 0.75. In terms of species abundance, 81% and 97% of species showed significant differences in IGC and MetaPhlAn2 among all groups with p < 0.05. Diversity showed significant differences across all groups, with decreasing differences of diversity between the experimental and the control groups following the increase in sequencing depth. The area under a receiver operating characteristic curve, AUC, of the obesity classifier for running the obesity testing samples showed an increasing trend following the increase in sequencing depth (τ = 0.29). The validation results were consistent with the above results. Our study found that the higher the sequencing depth is, the more the microbial information in structure and composition it provides. We also found that when sequencing depth was 15 million or higher, we obtained more stable species compositions and disease classifiers with good performance. Therefore, we recommend 15 million as the optimal minimum sequencing depth for an MWAS.

Endoscopic management of postoperative anastomotic bleeding in patients with colorectal cancer.

BACKGROUND: Postoperative anastomotic bleeding is considered a rare but life-threatening complication. There is no standard treatment strategy for this emergency condition. The aim of this study was to report our experiences in the management of postoperative anastomotic bleeding in patients with colorectal cancer. METHODS: We analyzed the general characteristics, treatments, and outcomes of patients with anastomotic bleeding after surgery for colorectal carcinoma at the Sixth Affiliated Hospital of Sun Yat-Sen University between July 2013 and September 2019 retrospectively. A univariate and multivariate analysis was performed to find protective factors for endoscopic hemostasis. Risk factors for anastomotic leakage after colonoscopy were also analyzed. RESULTS: A total of 9870 patients underwent surgeries for colorectal carcinoma between July 2013 and September 2019. Colonoscopies were performed in 78 cases with postoperative anastomotic bleeding. The effective rate of initial endoscopic hemostasis was 81% (63/78). In univariate and multivariate analysis, hemoclip therapy (odds ratio = 4.572; 95%CI 1.305-16.017; P = 0.017) and postoperative anastomotic bleeding within 5 days (odds ratio = 3.639; 95%CI 1.045-12.675; P = 0.042) are protective factors for endoscopic hemostasis. Comorbidity was associated with an increased risk for anastomotic leakage. CONCLUSIONS: Colonoscopy seems to be an effective way to achieve hemostasis for patients with anastomotic bleeding after surgery for colorectal carcinoma. It may be more effective in the early postoperative period, and hemoclip appears to be the first choice to control postoperative anastomotic bleeding.

Diverting colostomy is an effective procedure for ulcerative chronic radiation proctitis patients after pelvic malignancy radiation.

BACKGROUND: Chronic radiation proctitis (CRP) with rectal ulcer is a common complication after pelvic malignancy radiation, and gradually deteriorating ulcers will result in severe complications such as fistula. The aim of this study was to evaluate effect of colostomy on ulcerative CRP and to identify associated influence factors with effectiveness of colostomy. METHODS: Between November 2011 to February 2019, 811 hospitalized patients were diagnosed with radiation-induced enteritis (RE) in Sun Yat-sen University Sixth Affiliated Hospital, among which 284 patients presented with rectal ulcer, and 61 ulcerative CRP patients were retrospectively collected and analyzed. RESULTS: The overall effective rate of colostomy on ulcerative CRP was 49.2%, with a highest effective rate of 88.2% within 12 to 24 months after colostomy. 9 (31.1%) CRP patients with ulcers were cured after colostomy and 12 (19.67%) patients restored intestinal continuity, among which including 2 (3.3%) patients ever with rectovaginal fistula. 100% (55/55) patients with rectal bleeding and 91.4% (32/35) patients with anal pain were remarkably alleviated. Additionally, multivariable analysis showed the duration of stoma [OR 1.211, 95% CI (1.060-1.382), P = 0.005] and albumin (ALB) level post-colostomy [OR 1.437, 95% CI (1.102-1.875), P = 0.007] were two independent influence factors for the effectiveness of colostomy on the rectal ulcer of CRP patients. CONCLUSIONS: Colostomy was an effective and safe procedure for treating rectal ulcer of CRP patients, and also a potential strategy for preventing and treating fistula. Duration of stoma for 12-24 months and higher ALB level could significantly improve the effectiveness of colostomy on ulcerative CRP patients.

Clinical Anastomotic Leakage After Rectal Cancer Resection Can Be Predicted by Pelvic Anatomic Features on Preoperative MRI Scans: A Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: We demonstrated previously that radiation proctitis induced by preoperative radiotherapy is a predisposing factor for clinical anastomotic leakage in patients undergoing rectal cancer resection. Quantitative measurement of radiation proctitis is needed. OBJECTIVE: This study aimed to quantitate the changes of anatomic features caused by preoperative radiotherapy for rectal cancer and evaluate its ability to predict leakage. DESIGN: It was a secondary analysis of a randomized controlled trial (NCT01211210). MRI variables were retrospectively assessed. SETTINGS: The study was conducted in the leading center of the trial, which is a tertiary GI hospital. PATIENTS: Patients undergoing preoperative chemoradiation with sphincter-preserving surgery were included. MAIN OUTCOME MEASURES: Anatomic features were measured by preradiotherapy and postradiotherapy MRI. Univariate analyses were used to identify prognostic factors. Receiver operating characteristic curves were constructed to determine the cutoff value of the changes of MRI variables in predicting leakage. RESULTS: Eighteen (14.4%) of the 125 included patients developed clinical anastomotic leakage. Baseline characteristics were comparable between leakage group and nonleakage group. Relative increments of width of presacral space, thickness of rectal wall, and distal end of sigmoid colon discriminate between the 2 groups better than random chance. Relative increments of width of presacral space was the best performing predictor, with area under the curve of 0.722, sensitivity of 66.7%, specificity of 72.0%, and positive and negative predictive value of 28.6% and 92.8%. LIMITATIONS: The study was limited by its small sample size and retrospective design. CONCLUSIONS: Increments of the width of the presacral space, thickness of rectal wall, and distal part of the sigmoid colon helps to identify individuals not at risk for clinical anastomotic leakage after rectal cancer resection. The first variable is the strongest predictor. Changes of these variables should be taken into consideration when evaluating the application of defunctioning stoma. See Video Abstract at http://links.lww.com/DCR/B23. CLINICAL TRIALS IDENTIFIER: NCT1211210. LAS FUGAS ANASTOMÓTICAS CLÍNICAS DESPUÉS DE LA RESECCIÓN DEL CÁNCER DEL RECTO PUEDEN PREDECIRSE POR LAS CARACTERÍSTICAS ANATÓMICAS PÉLVICAS EN LAS IMAGENES DE RESONANCIA MAGNÉTICA PREOPERATORIA: UN ANÁLISIS SECUNDARIO DE UN ESTUDIO CONTROLADO ALEATORIZADO:: Anteriormente demostramos que la proctitis inducida por la radiación de radioterapia preoperatoria es un factor predisponente para la fuga anastomótica clínica en pacientes sometidos a resección de cáncer rectal. Es necesaria la medición cuantitativa de la proctitis por radiación.Este estudio tuvo como objetivo cuantificar los cambios en las características anatómicas causados por la radioterapia preoperatoria para el cáncer de recto y evaluar su capacidad para predecir las fugas anastomoticas.Fue un análisis secundario de un estudio controlado aleatorio (NCT01211210). Los variables de imagines de resonancia magnetica se evaluaron retrospectivamente.Se llevó a cabo en el centro principal del estudio, que es un hospital gastrointestinal terciario.Se incluyeron pacientes sometidos a quimiorradiación preoperatoria con cirugía conservadora del esfínter.Las características anatómicas se midieron mediante imagines de resonancia magnetica previa y posterior a la radioterapia. Se utilizaron análisis univariados para identificar los factores pronósticos. Las curvas de características operativas del receptor se construyeron para determinar el valor de corte de los cambios de los variables de resonancia magnetica en la predicción de fugas.Dieciocho (14.4%) de los 125 pacientes incluidos desarrollaron fugas anastomóticas clínicas. Las características basales fueron comparables entre el grupo de fugas y el grupo de no fugas. Los incrementos relativos del ancho del espacio presacro, el grosor de la pared rectal y distal del colon sigmoide discriminan entre los dos grupos mejor que la posibilidad aleatoria. Los incrementos relativos del ancho del espacio presacro fueron el mejor pronóstico con un AUC de 0.722, sensibilidad del 66.7%, especificidad del 72.0%, valor predictivo positivo y negativo del 28.6% y 92.8%.Estaba limitado por el tamaño de muestra pequeño y el diseño retrospectivo.Los incrementos en el ancho del espacio presacro, el grosor de la pared rectal y la parte distal del colon sigmoide ayudan a identificar a las personas que no tienen riesgo de fuga anastomótica clínica después de la resección del cáncer rectal. La primera variable es el predictor más fuerte. Los cambios de estos variables deben tenerse en cuenta al evaluar la aplicación del estoma para desvio. Vea el Resumen del Video en http://links.lww.com/DCR/B23.

Downregulation of miR-222-3p Reverses Doxorubicin-Resistance in LoVo Cells Through Upregulating Forkhead Box Protein P2 (FOXP2) Protein.

BACKGROUND Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat colon cancer. Despite impressive initial clinical responses, drug resistance has dramatically compromised the effectiveness of DOX. However, the underlying mechanisms of chemotherapeutic resistance in colon cancer remain poorly understood. MATERIAL AND METHODS In this study, we compared the expression of miR-222-3p in DOX-resistant colon cancer cells (LoVo/ADR) with the corresponding DOX-sensitive parental cells (LoVo/S) using quantitative real-time PCR. In addition, miR-222-3p inhibitors were infected into LoVo/ADR cell lines and the effects of this treatment were assessed. The Cell Counting Kit 8 assay was employed to verify the sensitivity of colon cancer cell lines to DOX. EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry, and in vivo subcutaneous tumorigenesis were used to assess cell proliferation and apoptosis. Transwell and wound healing assays were used to investigate cell migration after adding DOX. Additionally, the expression of forkhead box protein P2 (FOXP2), P-glycoprotein (P-gp) and caspase pathway-associated markers was assessed by western blotting. RESULTS Our results showed that miR-222-3p was upregulated in LoVo/ADR compared with the expression in LoVo/S cells. Additionally, downregulation of miR-222-3p in LoVo/ADR cells increased their sensitivity to DOX, reduced P-gp expression, and activated the caspase pathway. However, the downregulation of FOXP2 could efficiently reverse the effect of miR-222-3p inhibitors on LoVo/ADR cells. CONCLUSIONS Taken together, our results showed that miR-222-3p induced DOX resistance via suppressing FOXP2, upregulating P-gp, and inhibiting the caspase pathway.

[A clinical study of growth and metabolism of small for gestational age infants].

OBJECTIVE: To study the differences in growth and metabolism between small for gestational age (SGA) infants and appropriate for gestational age (AGA) infants. METHODS: A total of 1 370 preterm infants were enrolled in this study. According to the association between gestational age and birth weight, they were divided into SGA group with 675 infants and AGA group with 695 infants. The two groups were compared in terms of general conditions, physical growth and blood biochemical parameters. RESULTS: The SGA group had a significantly longer length of hospital stay than the AGA group (P<0.05). Compared with the AGA group, the SGA group had significantly lower body weight, body weight Z score, and body length at discharge and significantly higher incidence rate of extrauterine growth retardation and growth rate of head circumference (P<0.05). Compared with the AGA group, the SGA group had significantly longer time to full enteral nutrition and duration of parenteral nutrition (P<0.05). Compared with the AGA group, the SGA group had significantly higher levels of albumin, prealbumin, and serum phosphorus on admission and total bile acid before discharge, as well as a significantly lower albumin level before discharge (P<0.05). The incidence rates of asphyxia, neonatal respiratory distress syndrome, myocardial damage, feeding intolerance, pneumonia, sepsis, hypoglycemia and hypothyroxinemia in the SGA group were significantly higher than in the AGA group (P<0.05). CONCLUSIONS: Compared with AGA infants, SGA infants have significantly delayed physical development during hospitalization and significantly higher incidence rates of extrauterine growth retardation and related complications.

[Levels of blood free carnitine in preterm infants with different gestational ages and birth weights].

OBJECTIVE: To examine blood concentrations of free carnitine (FC) in preterm infants with different gestational ages (GA) and birth weights (BW). METHODS: A total of 3 368 preterm infants were enrolled as subjects. According to GA, they were divided into extremely preterm birth (EPTB) group (GA <28 weeks; n=39), very preterm birth (VPTB) group (28 ≤GA <32 weeks; n=405), moderately preterm birth (MPTB) group (32 ≤GA <34 weeks; n=507), and late preterm birth (LPTB) group (34 ≤GA <37 weeks; n=2 417); according to BW, they were divided into extremely low birth weight (ELBW) group (BW <1 000 g; n=36), very low birth weight (VLBW) group (1 000 g ≤BW <1 500 g; n=387), low birth weight (LBW) group (1 500 g ≤BW <2 500 g; n=1 873), and normal birth weight (NBW) group (2 500 g ≤ BW <4 000 g; n=1 072). Blood concentrations of FC were measured between 72 hours and 7 days after birth. RESULTS: The EPTB and VPTB groups had significantly higher FC concentrations than the MPTB and LPTB groups (P<0.05), and the MPTB group had significantly higher FC concentrations than the LPTB group (P<0.05). The lower limit of the 95% medical reference range of FC increased with the reduction in GA. The ELBW and VLBW groups had significantly higher FC concentrations than the LBW and NBW groups (P<0.05). The LBW group had significantly higher FC concentrations than the NBW group (P<0.05). The lower limit of the 95% medical reference range of FC increased with the reduction in BW. CONCLUSIONS: There is a significant increase in blood FC concentrations in very/extremely preterm infants and very/extremely low birth weight infants, and tend to decrease with the increases in GA and BW.

[Clinical application of whole exome sequencing in monogenic hereditary disorders in critically ill newborns].

OBJECTIVE: To explore the value and significance of the clinical application of whole exome sequencing (WES) in monogenic hereditary disorders in critically ill newborns. METHODS: The critically ill newborns in the neonatal intensive care unit with suspected hereditary diseases or unclear clinical diagnosis from June 2016 to December 2018 were enrolled. The whole blood samples from both newborns and parents were collected for WES. The detected genetic mutations were classified, the mutations associated with clinical phenotypes were searched for, and Sanger sequencing was performed to verify the mutations. RESULTS: A total of 45 newborns were enrolled, including 22 males and 23 females, and the median age of onset was 2.0 days. Of the 45 newborns, 12 (27%) were confirmed with monogenic hereditary disorders by molecular diagnostics, and the median age at diagnosis was 31.5 days. Of the 12 newborns with monogenic hereditary disorders, 5 (42%) were partially associated with clinical phenotypes but confirmed with monogenic hereditary disorders by additional information supplement and analysis. The improvement rate of newborns with monogenic hereditary disorders was 67% (8/12) after treatment. CONCLUSIONS: WES technology is a powerful tool for finding genetic mutations in monogenic hereditary disorders in critically ill newborns and can play a crucial role in clinical decision-making. However, a comprehensive interpretation of sequence data requires physicians to take the clinical phenotypes and the results of WES into consideration simultaneously.

[Effect of prone positioning on respiratory function in very preterm infants undergoing mechanical ventilation].

OBJECTIVE: To explore the effect of prone positioning on respiratory function in very preterm infants undergoing mechanical ventilation. METHODS: A total of 83 very preterm infants treated with mechanical ventilation were enrolled in the study and were randomly assigned to supine group and prone group. Four infants withdrew from the study and 79 infants completed treatment and observation (37 in the supine group and 42 in the prone group). Infants in both groups were mechanically ventilated in a volume assist-control mode. Infants in the prone group were ventilated in the supine position for 4 hours and in the prone position for 2 hours. Ventilator parameters, arterial blood gas analysis, and vital signs were recorded before grouping, every 6 hours in the supine group, and every hour after conversion into the prone position in the prone group, respectively. RESULTS: Fraction of inspired oxygen (FiO2), peak inspiratory pressure, mean inspiratory pressure, and duration of ventilation were significantly lower in the prone group than in the supine group (P<0.05); there were no significant differences in tidal volume or positive end-expiratory pressure between the two groups (P>0.05). The prone group had a significantly higher PO2/FiO2 ratio but significantly lower oxygenation index and respiratory rate than the supine group (P<0.05). There were no significant differences in arterial oxygen tension, pH, base excess, heart rate, or mean blood pressure between the two groups (P>0.05). CONCLUSIONS: Alternating ventilation between the prone position and supine position can improve oxygenation function, decrease the fraction of inspired oxygen, and shorten the duration of mechanical ventilation in very preterm infants undergoing mechanical ventilation.

Investigation of correlation between mutational status in key EGFR signaling genes and prognosis of stage II colorectal cancer.

AIM: To investigate the relationship between mutations of key genes in the EGFR signaling pathway and the prognosis of stage II colorectal cancer patients without chemotherapy. MATERIALS & METHODS: The incidence of KRAS, NRAS, BRAF, PIK3CA mutations and deficient DNA mismatch repair were assessed in 160 stage II colorectal cancer patients who had been treated by radical operation without adjuvant chemotherapy. RESULTS: Mutations in KRAS, BRAF or PIK3CA were associated with poor prognosis, while the deficient DNA mismatch repair status was not associated with the prognosis. Combining these three markers, the sensitivity of the predicted value for poor progression-free survival and overall survival reached 0.645 (p = 0.002) and 0.709 (p = 0.001), respectively. CONCLUSION: Knowing the mutation status of KRAS, BRAF or PIK3CA in stage II colorectal cancer can significantly improve the accuracy of prognoses.

Restorative resection of radiation rectovaginal fistula can better relieve anorectal symptoms than colostomy only.

BACKGROUND: Radiation-induced rectovaginal fistula (RVF) is a severe and difficult complication after pelvic malignancy radiation. This study was to retrospectively compare the outcomes of restorative resection and colostomy only in remission of anorectal symptoms. METHODS: We enrolled a cohort of 26 consecutive cases who developed RVF after pelvic radiation. Two main procedures for these patients in our institution were used: one was restorative resection and pull-through coloanal anastomosis with a prophylactic colostomy, and another was a simple colostomy without resection. Thus, we divided these patients into these two groups. Anorectal symptoms including rectal pain, bleeding, tenesmus, and perineal mucous discharge were recorded and scored prior to surgery and at postoperative multiple time points. RESULTS: The baseline was similar among the two groups. All patients acquired good efficacy with improved symptoms at postoperative 6, 12, and 24 months, when compared to baseline. In addition, the resection group showed a better remission of tenesmus (6 months 33.3 vs 0%; 12 months 66.7 vs 16.7%) and perineal mucous discharge (6 months 88.9 vs 6.7%; 12 months 77.8 vs 15.4%; 24 months 85.7 vs 25.0%). Furthermore, three (30%) patients in the resection group successfully reversed stomas while no stoma was closed in the simple colostomy group. CONCLUSIONS: Both restorative resection procedure and colostomy only can improve anorectal symptoms of radiation-induced RVF, but restorative resection can completely relieve anorectal symptoms in selected cases.

[Prevalence and risk factors of arrhythmias after transcatheter closure of ventricular septal defect in children].

OBJECTIVE: To evaluate the prevalence and risk factors of arrhythmia after transcatheter closure of ventricular septal defect (VSD) in children. METHODS: A total 1 069 children (583 males, mean age (7.7 ± 3.6) years) underwent transcatheter closure of VSD from January 2002 to December 2010 in our hospital were enrolled and retrospectively analyzed.VSD diameters were (4.0 ± 1.8)mm, 336 cases accompanied membranous aneurysm. Electrocardiogram were performed at 1, 3 days after the procedure.Once arrhythmias recorded, electrocardiogram was performed daily till discharge. All cases were followed up by ECG at 1, 3, 6, 12 months after the procedure in outpatient department and then in a year interval. The risk factors were identified by multivariable logistical analysis. RESULTS: All VSDs were closed successfully and the diameters of occluder was (7.2 ± 2.1)mm. The median follow-up time was 2.2 (1.0-4.2) years. Mortality was zero during follow up.Incidence of early ( < 1 month) post-procedure arrhythmias was 24.6 % (263 cases), and severe arrhythmias were recorded in 50 cases (4.7%). There were 43 late ( ≥ 1 month) post-procedure arrhythmias (4.0%) including 4 (0.4%) complete atrioventricular block. Multivariable logistic analysis revealed that VSD treated with thin-waist-big-side occluder (OR = 2.426, 95%CI:1.835-3.208, P < 0.001) , male gender (OR = 1.267, 95%CI:1.055-1.523, P = 0.011) were the risk factors while higher body weight (OR = 0.838, 95%CI:0.737-0.951, P = 0.006) was protective factor for early onset arrhythmia. Placement of asymmetrical occluder (OR = 4.777, 95%CI:2.079-10.978, P < 0.001) , longer procedure time (OR = 1.011, 95%CI:1.002-1.020, P = 0.012) , occluder from foreign countries (OR = 2.621, 95%CI:1.143-6.014, P = 0.021) were the risks factors for early onset severe conduct block. Treatment with thin-waist-big-side occluder (OR = 2.654, 95%CI: 1.042-6.760, P = 0.041) was the risk factor while higher body weight (OR = 0.373, 95%CI:0.159-0.875, P = 0.023) was a protective factor for late onset conduct block. CONCLUSIONS: Arrhythmia after transcatheter closure of VSD is common in children, and late onset severe conduct block is rare. The weight of patients should not too light and symmetrical occluder should be chosen if possible in the transcatheter closure VSD procedure to minimize the risk of late onset conduct block.

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration.

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.

[Feature extraction of myocardial infarction based on lead I ECG].

This paper presents a myocardial infarction feature extraction algorithm, and whereby using single-cycle signal of electrocardiogram (ECG) lead I, we solved the problem of inconvenience in using multi-lead ECG. Firstly, the noise is eliminated from the signal of ECG lead I, and then, wavelet packet algorithm is introduced to extract the main frequency band of QRS complex and T wave, and reconstruct the QRS complex and T wave shape so as to determine the original and end positions of ST segment. Finally, ST segment is decomposed and the waveform characteristics of myocardial infarction from ECG lead I signal is obtained based on the analysis of wavelet's multi-resolution. Simulation results showed that the algorithm achieved a high recognition rate, which provides fundamental principle for the detection of myocardial infarction by using the ECG lead I signal.

Synthesis and luminescence properties of Mn-doped Cs2KBiCl6 double perovskite phosphors.

Novel lead-free double perovskite phosphors of Mn-doped Cs2KBiCl6 (Cs2KBiCl6:Mn2+) have been facilely synthesized by using typical hydrothermal method. X-ray diffraction, scanning electron microscope, X-ray photoelectron spectroscopy, electron paramagnetic resonance, and photoluminescence measurements confirm that the synthesized Cs2KBiCl6:Mn2+ phosphors behave double perovskite structure, good morphology, excellent stability, and superior optical properties. An optimal doping concentration of Mn/Bi = 0.4 is achieved in Cs2KBiCl6:Mn2+ phosphors, showing maximum photoluminescence quantum yield of 87.2%, lifetime of 0.98 ms, and orange-red fluorescence with the emission peak at 595 nm under UV light excitation. The probable luminescence mechanism could be ascribed to excitation energy transferring from Cs2KBiCl6 to Mn, and accordingly contributing to the 4T1-6A1 transition of the Mn d electron. Superb optical properties provide much room for in-depth fluorescence researches and potential applications of Cs2KBiCl6:Mn2+ phosphors.