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1.
BMC Musculoskelet Disord ; 25(1): 373, 2024 May 11.
Article En | MEDLINE | ID: mdl-38730376

INTRODUCTION: An acute Achilles tendon rupture represents a common tendon injury, and its operative methods have been developed over the years. This study aimed to quantify the learning curve for the minimally invasive acute Achilles tendon rupture repair. METHODS: From May 2020 to June 2022, sixty-seven patient cases who received minimally invasive tendon repair were reviewed. Baseline data and operative details were collected. The cumulative summation (CUSUM) control chart was used for the learning curve analyses. Achilles tendon rupture score (ATRS), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot score, and visual analog scale (VAS) at 3/6/9/12 months were calculated to assess the clinical outcomes. RESULTS: Thirty-six cases underwent at least a year of follow up and were enrolled in this study. The gender ratio and average age were 80.5% and 32.5 years. The linear equation fitted well (R2 = 0.95), and CUSUM for operative time peaked in the 12th case, which was divided into the learning phase (n = 12) and master phase (n = 24). No significant difference was detected between the two groups in clinical variables, except for the operative time (71.1 ± 13.2 min vs 45.8 ± 7.2 min, p = 0.004). Moreover, we detected one case with a suture reaction and treated it properly. CONCLUSION: Minimally invasive Achilles repair provides an opportunity for early rehabilitation. Notably, the learning curve showed that the "lumbar puncture needle and oval forceps" technique was accessible to surgeons.


Achilles Tendon , Learning Curve , Minimally Invasive Surgical Procedures , Tendon Injuries , Humans , Achilles Tendon/surgery , Achilles Tendon/injuries , Male , Female , Adult , Minimally Invasive Surgical Procedures/methods , Minimally Invasive Surgical Procedures/education , Minimally Invasive Surgical Procedures/instrumentation , Middle Aged , Tendon Injuries/surgery , Rupture/surgery , Retrospective Studies , Treatment Outcome , Surgical Instruments , Needles , Operative Time
2.
Front Surg ; 11: 1293049, 2024.
Article En | MEDLINE | ID: mdl-38425376

Backgrounds: This study aims to evaluate the clinical outcome of intramedullary nail supplemented by buttress plate or cable in the treatment of intertrochanteric fracture with broken lateral wall. Methods: From May 2015 to January 2022, patients with unstable intertrochanteric femoral fractures underwent intramedullary fixations strengthened with buttress plates or cables, which depended on the lateral femur wall fragment type. The clinical and radiographic results were compared between the two groups. The hip function was evaluated according to the Harris Hip Scoring (HHS) system. Results: Forty-one patients who sustained intertrochanteric fracture + broken lateral wall were enrolled. Of these, thirty-four received a minimum of twelve months of follow-ups. No statistically significant differences in baseline and operative data were proved between these groups (p > 0.05). Three patients were observed fat liquefaction after surgery (plate group: 2 cases, cable group: 1 case). All patients could sustain partial/full weight-bearing and no case underwent subsequent operation. The HHS of the last follow-up presented 83.6 ± 4.9 points in the plate group and 83.8 ± 3.7 points in the cable group. Conclusions: Intertrochanteric femoral fracture with broken lateral wall is an unstable injury type, the operative treatments of which have been challenging and controversial over the years. Augmentation of intramedullary nailing system using plate/cable contributes to reconstructing the lateral femur wall.

3.
Int J Gen Med ; 17: 323-334, 2024.
Article En | MEDLINE | ID: mdl-38314199

Background: This study aimed to create three-dimensional heat map and study the characteristic of fracture lines and represented fragments of OTA/AO type 43C pilon fractures. Methods: CT scan was performed in105 fractures diagnosed with OTA/AO type 43C pilon fractures between January 2017 and December 2022. Three-dimensional pilon fracture maps were created and converted into fracture heat maps. CT scan graphic parameters including the fracture line height, α angle, ß angle, the ratio of the area and size of bone fragment represented by the fracture line to the total articular surface were measured. Results: The study included 105 patients with 91 males and 14 females. The fractures included C1 (n=16), C2 (n=23), and C3 (n=66). There was no statistically different among the most parameters except in the fracture-line height of the anterior fracture line (p=0.03) and the sagittal fracture line (p=0.02) between C2 and C3 pilon fractures. The average size of the anterolateral fragment, occupied approximately 13.5% of the articular surface area, was (11.5±2.8) mm × (20.5±6.3) mm with the average height of 29.8 mm. The average size of the posterolateral fragment, occupied approximately 13.0% of the articular surface area, was (15.7±4.6) mm × (19.3±4.0) mm with the average height of 19.1 mm. Conclusion: This study demonstrates that the articular surface fracture lines in the C type pilon fracture are formed by fixed main fracture lines. The understand of morphological and distribution characteristics of the fracture lines and size of fragments in OTA/AO type 43C pilon fractures would help the surgeons take suitable approach and fixation.

4.
PeerJ ; 12: e16918, 2024.
Article En | MEDLINE | ID: mdl-38371376

Ovarian cancer is a complex polygenic disease in which genetic factors play a significant role in disease etiology. A genome-wide association study (GWAS) identified a novel variant on chromosome 9q22.33 as a susceptibility locus for epithelial ovarian cancer (EOC) in the Han Chinese population. However, the underlying mechanism of this genomic region remained unknown. In this study, we conducted a fine-mapping analysis of 130 kb regions, including 1,039 variants in 200 healthy women. Ten variants were selected to evaluate the association with EOC risk in 1,099 EOC cases and 1,591 controls. We identified two variants that were significantly associated with ovarian cancer risk (rs7027650, P = 1.91 × 10-7; rs1889268, P = 3.71 × 10-2). Expression quantitative trait locus (eQTL) analysis found that rs7027650 was significantly correlated with COL15A1 gene expression (P = 0.009). The Luciferase reporter gene assay confirmed that rs7027650 could interact with the promoter region of COL15A1, reducing its activity. An electrophoretic mobility shift assay (EMSA) showed the allele-specific binding capacity of rs7027650. These findings revealed that rs7027650 could be a potential causal variant at 9q22.33 region and may regulate the expression level of COL15A1. This study offered insight into the molecular mechanism behind a potential causal variant that affects the risk of ovarian cancer.


Genetic Predisposition to Disease , Ovarian Neoplasms , Female , Humans , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Ovarian Neoplasms/genetics , Quantitative Trait Loci/genetics , Carcinoma, Ovarian Epithelial/genetics , Chromosome Structures
5.
Arch Orthop Trauma Surg ; 144(1): 59-71, 2024 Jan.
Article En | MEDLINE | ID: mdl-37624429

BACKGROUND: Optimal surgical fixation for displaced intra-articular calcaneal fractures (DIACF) remains a subject of debate, particularly regarding the superiority between screw fixation and plate fixation via the sinus tarsi approach (STA). This review aims to determine the preferred treatment for DIACF and compare the outcomes of minimally invasive surgery options. METHODS: Our study involved thorough searches across multiple electronic databases, including PubMed, Cochrane, Embase, and Web of Science, to identify all relevant publications on distal intra-articular fractures of the calcaneus (DIACFs) that were fixed using cannulated screws or plates via STA. Through a comprehensive meta-analysis, we evaluated several outcomes, including post-operative function, radiological measurements, and complications. RESULT: A total of 728 patients from 7 studies met the inclusion criteria. Among them, 435 patients underwent screw fixation via STA, and 373 patients underwent plate fixation via STA. The study found no statistically significant differences between the screw fixation and the plate fixation via sinus tarsi approach (STA) in terms of AOFAS scores, Bohler's angle, Gissane's angle, sural nerve injury, secondary subtalar arthrodesis and reoperation. Compared with screw fixation, plate fixation via STA can reduce reduction loss of Bohler's angle (WMD = - 1.64, 95% CI = [- 2.96, - 0.31], P = 0.06, I2 = 59%), lower the incidence of fixation failure (OR = 0.32, 95% CI = [0.13, 0.81], P = 0.78, I2 = 0%), and decrease intra-articular step-off (WMD = - 0.52, 95% CI = [- 0.87, - 0.17], P = 0.66, I2 = 0%). CONCLUSIONS: Plate fixation demonstrates superior capability in restoring calcaneal width, maintaining Bohler's angle, and minimizing intra-articular step-off, thereby maintaining better reduction of the subtalar articular surface. In addition, plate fixation exhibits the modest complication rate and a low incidence of fixation failure. Therefore, we recommend the use of plate fixation through the STA, especially for complex and comminuted intra-articular calcaneal fractures.


Ankle Injuries , Calcaneus , Foot Injuries , Fractures, Bone , Intra-Articular Fractures , Humans , Ankle Injuries/surgery , Bone Screws , Calcaneus/surgery , Calcaneus/injuries , Fracture Fixation, Internal , Fractures, Bone/surgery , Heel/surgery , Intra-Articular Fractures/surgery , Treatment Outcome
6.
J Orthop Surg Res ; 18(1): 978, 2023 Dec 20.
Article En | MEDLINE | ID: mdl-38124085

BACKGROUND: Approach need to be considered when surgeons dealt with complex elbow injuries and the choice of the approach is a challenge for surgeons due to the complex anatomy. On the basis of releasing the lateral collateral ligament, we modified the dislocation technique to pursue the superior exposure including not only the distal humeral surface but also the anterior facet of the coronoid process. METHODS: A total of 4 cadaver specimens and 8 elbows were included in the study. Each cadaver provided one elbow for either the elbow dislocation approach or the posterior olecranon approach. The exposed distal articular surface of humerus, humeral capitulum, humeral trochlea, anterior trochlea of distal humerus, posterior trochlea of distal humerus and the ulnar coronoid process surface were marked by image J software and calculated for a comparison for each surgical approach. RESULTS: The total distal humeral surface was exposed as a median of 98.2 (97.6, 99.6)% and 62.0 (58.3, 64.5)% for the elbow dislocation approach and the olecranon osteotomy approach (P < 0.001), the capitulum 100% and 32.4 (28.0, 39.2)% (P < 0.001), the trochlea 93.2(90.1, 96.9)% and 72.5 (65.2, 78.8)% (P < 0.001), the anterior trochlear articular surface 96.0(93.0, 97.4)% and 50.3 (43.6, 59.1)% (P < 0.001), the posterior trochlear articular surface 95.4 (93, 100)% and 100% (P = 0.76) and the articular surface of the coronoid process of ulna 71.3 (66.0, 74.2)% and 0% (P < 0.001). CONCLUSION: For complex elbow fractures, the technique of elbow dislocation provides complete exposure of the distal humerus surface and a significant portion of the coronoid process surface, facilitating direct visualization for reduction and fixation. Level of evidence Anatomy Study; Cadaver Dissection.


Elbow Fractures , Elbow Joint , Humeral Fractures , Joint Dislocations , Humans , Elbow/surgery , Elbow Joint/surgery , Humerus/surgery , Joint Dislocations/surgery , Cadaver , Humeral Fractures/surgery , Fracture Fixation, Internal
7.
J Orthop Surg Res ; 18(1): 866, 2023 Nov 14.
Article En | MEDLINE | ID: mdl-37964306

BACKGROUND: Approximately 20% of acute ankle sprains progress to chronic lateral ankle instability (CLAI) requiring surgical intervention. There has been growing interest among surgeons regarding whether arthroscopic techniques can replace open Brostrom-Gould surgery in treating CLAI. The purpose of this study was to pool the results of multiple studies comparing the treatment effects of these two fixation approaches. METHODS: Our study involved thorough searches across multiple electronic databases, including PubMed, Cochrane, Embase, and Web of Science, to identify all relevant publications on CLAI that were repaired using the arthroscopic or open Broström-Gould technique. Through a comprehensive meta-analysis, we evaluated several outcomes, including post-operative function, radiological measurements, complications, and time efficiency. RESULT: A total of 686 patients from 11 studies were included in the analysis. Among them, 351 patients underwent open repair, and 335 underwent arthroscopic Brostrom-Gould surgery. The present study revealed that arthroscopic and open Brostrom-Gould techniques demonstrated no significant differences in talar tilt, talar anterior translation, complication rate, and time to return to previous level of activity. Furthermore, no significant differences were observed in AOFAS, K-P, VAS, and Tegner scores at the 2-year follow-up. However, significant differences were noted between the two surgical approaches in terms of early weight-bearing (WMD = - 1.33 weeks, 95% CI = [- 1.91, - 0.76], P = 0.17, I2 = 40%), as well as AOFAS scores (WMD = 1.00, 95% CI = [0.05, 1.95], P = 0.73, I2 = 0%), K-P scores (WMD = 1.57, 95% CI = [0.49, 2.64], P = 0.15, I2 = 47%), and VAS scores (WMD = - 0.15, 95% CI = [- 0.60, 0.29], P < 0.08, I2 = 61%) within the first postoperative year. CONCLUSIONS: Our findings support that arthroscopic repair yields comparable outcomes to open surgery. Consequently, we advocate for adopting arthroscopic repair as a preferred alternative to the conventional open Broström-Gould procedure for treating chronic lateral ankle instability.


Joint Instability , Lateral Ligament, Ankle , Humans , Lateral Ligament, Ankle/surgery , Ankle Joint/diagnostic imaging , Ankle Joint/surgery , Ankle , Arthroscopy/methods , Radiography , Joint Instability/diagnostic imaging , Joint Instability/surgery , Retrospective Studies
8.
Cancer Med ; 12(14): 14937-14948, 2023 Jul.
Article En | MEDLINE | ID: mdl-37387469

BACKGROUND: Traditional human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) is recommended to be divided into HER2-low and HER2-zero subtypes due to different prognosis. However, few studies investigated their differences in clinical characteristics and prognosis among Chinese HER2-negative BC and their stratified differences by hormone receptor (HR), while fewer studies investigated their differences in epidemiological factors and genetic susceptibility. METHODS: A total of 11,911 HER2-negative BC were included to compare the clinical characteristics and prognosis between HER2-zero and HER2-low BC, and 4227 of the 11,911 HER2-negative BC were further compared to 5653 controls to investigate subtype-specific epidemiological factors and single nucleotide polymorphisms(SNPs). RESULTS: Overall, 64.2% of HER2-negative BC were HER2-low BC, and the stratified proportions of HER2-low BC were 61.9% and 75.2% for HR-positive and HR-negative BC, respectively. Compared to HER2-zero BC, HER2-low BC among HR-positive BC showed younger age at diagnosis, later stage, poorer differentiation, and higher Ki-67, while elder age at diagnosis and lower mortality were observed for HER2-low BC among HR-negative BC (all p values <0.05). Compared to healthy controls, both HER2-low and HER2-zero BC are associated with similar epidemiological factors and SNPs. However, stronger interaction between epidemiological factors and polygenic risk scores were observed for HER2-zero BC than HER2-low BC among either HR-positive [odds ratios: 10.71 (7.55-15.17) and 8.84 (6.19-12.62) for the highest risk group compared to the lowest risk group] or HR-negative BC [7.00 (3.14-15.63) and 5.70 (3.26-9.98)]. CONCLUSIONS: HER2-low BC should deserve more attention than HER2-zero BC, especially in HR-negative BC, due to larger proportion, less clinical heterogeneity, better prognosis, and less susceptibility to risk factors.

9.
Cancer Med ; 12(6): 7498-7507, 2023 03.
Article En | MEDLINE | ID: mdl-36415180

BACKGROUND: ABO blood groups has been associated with risk of several cancers; however, the results for an association with ovarian cancer are inconsistent and little is known about the expression of histo-blood group (ABH) antigens and ABO gene in ovarian tumor tissues. METHODS: To assess the impact of genotype-derived ABO blood types on the risk of EOC, we conducted a case-control study in 1,870 EOC and 4,829 controls. Expression of A and B antigen in 70 pairs of ovarian tumor tissues and adjacent normal tissues were detected by immunohistochemistry. Gene expression and DNA methylation profiling was conducted in ovarian tumor tissues. RESULTS: We identified that blood group A was associated with increased risk for EOC compared to blood group O (OR = 1.18, 95% CI = 1.03-1.36, p = 0.019). Increased frequency of aberrant expression of histo-blood group antigens was observed in patients with blood group A (76.5%) compared to patients with blood group O (21.1%) and B (5.0%) by immunohistochemistry (p < 0.001). ABO gene expression was down-regulated in ovarian tumor tissues compared with paired adjacent normal tissues (p = 0.027). In addition, ABO gene expression was positively correlated with NFYB (r = 0.38, p < 0.001) and inversely correlated with DNA methylation level of four CpG sites on ABO gene (cg11879188, r = - 0.3, p = 0.002; cg22535403, r = - 0.30, p = 0.002; cg13506600, r = - 0.22, p = 0.025; cg07241568, r = - 0.21, p = 0.049) in ovarian tumor tissues. CONCLUSION: We identified blood group A was associated with increased EOC risk in Chinese women and provided the clues of the possible molecular mechanisms of blood group A related to ovarian cancer risk.


ABO Blood-Group System , Ovarian Neoplasms , Humans , Female , Carcinoma, Ovarian Epithelial/genetics , ABO Blood-Group System/genetics , Case-Control Studies , East Asian People , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology
10.
Knee ; 35: 149-156, 2022 Mar.
Article En | MEDLINE | ID: mdl-35313243

BACKGROUND: Ten-segment classification provides a different approach to the evaluation of tibial plateau fractures. The purpose of this study was to assess the intra- and inter-observer reliability of three widely used classification systems (Schatzker, Arbeitsgemeinschaft für Osteosynthesefragen (AO/OTA), and the updated three-column concept (uTCC)) with ten-segment classification in two-dimensional computed tomography (2D-CT) and three-dimensional computed tomography (3D-CT). METHOD: Ninety 2D-CT and 3D-CT scans of patients with tibial plateau fractures were included in this retrospective cohort study. The included data were independently classified by six observers of different years of seniority and were independently observed and classified again after eight weeks. Inter-observer and intra-observer reliability of the four fracture classifications made by the six observers was analyzed using the kappa statistic. Kappa values were interpreted according to the categorical rating by Landis and Koch. RESULTS: When the inter-observer reliability was based on 2D-CT/3D-CT analysis, the mean Kappa values for the Schatzker, AO/OTA, uTCC, and ten-segment classification were 0.64/0.66, 0.56/0.59, 0.53/0.65, and 0.60/0.73, respectively. When intra-observer reliability was based on 2D-CT/3D-CT, the mean Kappa values for the Schatzker, AO/OTA, uTCC, and ten-segment classification were 0.68/0.83, 0.69/0.83, 0.74/0.85, and 0.80/0.91, respectively. CONCLUSIONS: The use of 3D-CT is important for the reliable diagnosis and recognition of tibial plateau fracture features compared to 2D-CT. When using 3D-CT, ten-segment classification showed high intra- and inter-observer agreement.


Tibial Fractures , Humans , Observer Variation , Reproducibility of Results , Retrospective Studies , Tibial Fractures/diagnostic imaging , Tomography, X-Ray Computed/methods
11.
Cell Discov ; 7(1): 121, 2021 Dec 21.
Article En | MEDLINE | ID: mdl-34930913

Ovarian cancer survival varies considerably among patients, to which germline variation may also contribute in addition to mutational signatures. To identify genetic markers modulating ovarian cancer outcome, we performed a genome-wide association study in 2130 Chinese ovarian cancer patients and found a hitherto unrecognized locus at 3p26.1 to be associated with the overall survival (Pcombined = 8.90 × 10-10). Subsequent statistical fine-mapping, functional annotation, and eQTL mapping prioritized a likely casual SNP rs9311399 in the non-coding regulatory region. Mechanistically, rs9311399 altered its enhancer activity through an allele-specific transcription factor binding and a long-range interaction with the promoter of a lncRNA BHLHE40-AS1. Deletion of the rs9311399-associated enhancer resulted in expression changes in several oncogenic signaling pathway genes and a decrease in tumor growth. Thus, we have identified a novel genetic locus that is associated with ovarian cancer survival possibly through a long-range gene regulation of oncogenic pathways.

12.
Front Genet ; 12: 646179, 2021.
Article En | MEDLINE | ID: mdl-33815481

Identifying causal regulatory variants and their target genes from the majority of non-coding disease-associated genetic loci is the main challenge in post-Genome-Wide Association Studies (GWAS) functional studies. Although chromosome conformation capture (3C) and its derivative technologies have been successfully applied to nominate putative causal genes for non-coding variants, many GWAS target genes have not been identified yet. This study generated a high-resolution contact map from epithelial ovarian cancer (EOC) cells with two H3K27ac-HiChIP libraries and analyzed the underlying gene networks for 15 risk loci identified from the largest EOC GWAS. By combinatory analysis of 4,021 fine-mapped credible variants of EOC GWAS and high-resolution contact map, we obtained 162 target genes that mainly enriched in cancer related pathways. Compared with GTEx eQTL genes in ovarian tissue and annotated proximal genes, 132 HiChIP targets were first identified for EOC causal variants. More than half of the credible variants (CVs) involved interactions that were over 185 kb in distance, indicating that long-range transcriptional regulation is an important mechanism for the function of GWAS variants in EOC. We also found that many HiChIP gene targets showed significantly differential expressions between normal ovarian and EOC tumor samples. We validated one of these targets by manipulating the rs9303542 located region with CRISPR-Cas9 deletion and dCas9-VP64 activation experiments and found altered expression of HOXB7 and HOXB8 at 17q21.32. This study presents a systematic analysis to identify putative target genes for causal variants of EOC, providing an in-depth investigation of the mechanisms of non-coding regulatory variants in the etiology and pathogenesis of ovarian cancer.

13.
Aging (Albany NY) ; 13(1): 1332-1356, 2020 12 03.
Article En | MEDLINE | ID: mdl-33291081

Genome-wide association studies have revealed that multiple single-nucleotide polymorphisms in the intergenic region between estrogen receptor 1 and coiled-coil domain containing 170 (CCDC170) are associated with breast cancer risk. We performed microarray and bioinformatics analyses to identify genes that were induced upon CCDC170 overexpression, and confirmed our findings by evaluating paraffin-embedded breast cancer tissues and conducting cellular assays. In CCDC170-overexpressing MCF7 breast cancer cells, microarray analyses revealed that inositol-requiring enzyme 1 (IRE1) was the most elevated gene in enriched pathways. In breast cancer tissues, IRE1 expression correlated positively with CCDC170 and X-box binding protein 1 expression at both the mRNA and protein levels. In a survival analysis, patients with higher CCDC170 levels exhibited better disease-free survival. Western blotting indicated that overexpressing CCDC170 in MCF7 cells increased protein levels of IRE1α, estrogen receptor α and X-box binding protein 1, while silencing CCDC170 reduced them. CCDC170 overexpression promoted apoptosis in MCF7 cells, and this effect was more obvious under endoplasmic reticulum stress. MCF7 cells overexpressing CCDC170 were more sensitive to paclitaxel. Our study showed that higher CCDC170 expression is associated with a better prognosis in breast cancer patients and that CCDC170 may promote apoptosis through the IRE1α pathway.


Apoptosis/genetics , Breast Neoplasms/genetics , Carcinoma, Ductal, Breast/genetics , Endoribonucleases/genetics , Protein Serine-Threonine Kinases/genetics , Adult , Aged , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Carrier Proteins/genetics , Carrier Proteins/metabolism , Disease-Free Survival , Endoplasmic Reticulum Stress/genetics , Endoribonucleases/metabolism , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Female , Humans , MCF-7 Cells , Middle Aged , Paclitaxel/pharmacology , Polymorphism, Single Nucleotide , Protein Serine-Threonine Kinases/metabolism , Transcriptome , X-Box Binding Protein 1/genetics , X-Box Binding Protein 1/metabolism
14.
Gynecol Oncol ; 158(1): 178-187, 2020 07.
Article En | MEDLINE | ID: mdl-32362568

OBJECTIVE: Extensive genetic and limited epigenetics have been characterized by the Cancer Genome Atlas (TCGA) among Western High-grade serous ovarian cancer (HGSOC). The present study aimed to characterize Chinese HGSOC at genome scale. METHODS: We used reduced representation bisulfite sequencing to investigate whole-genome and tumor-specific DNA methylation in 21 HGSOC tumors paired with their normal tissues, followed by a replication study involving additional 41 HGSOC patients. Altered methylation patterns in HGSOC were further characterized by gene expression profiles and whole-exome sequencing data. RESULTS: Comparing HGSOC tumors with normal tissues we observed global hypomethylation but with more specific hypermethylation in gene promoter. Totally, we revealed 159,881 differentially methylated regions (DMRs) and 4060 differentially expressed genes (DEGs). By integrating DNA methylation and mRNA expression data, we identified 153 negative (mainly in the upstream region) and 115 positive (mainly in the CDS regions) DMRs-DEGs correlated pairs, respectively. The negatively correlated DMRs-DEGs underlined Wnt and cell adhesion molecule binding as critical canonical pathways disrupted by DNA methylation. Eleven DMRs (in CAPS, FZD7, CDKN2A, PON3, KLF4, etc.), accompanied with a global DNA methylation marker, were validated in the replication samples. Whole-exome sequencing presented a relatively less dominated TP53 mutation in Chinese HGSOC compared to TCGA dataset. Unsupervised analysis of the three-level omics data identified differential methylation and expression subgroups based on tumor genetics, one of which presented increased DNA methylation and significantly associated with TP53 mutation. CONCLUSIONS: Our individual and integrated analyses contribute details about the tissue-specific genetic and DNA methylation landscape of Chinese HGSOC.


Cystadenocarcinoma, Serous/genetics , DNA Methylation , Ovarian Neoplasms/genetics , Asian People/genetics , Cystadenocarcinoma, Serous/pathology , Epigenesis, Genetic , Female , Gene Expression Profiling , Genotype , Humans , Kruppel-Like Factor 4 , Mutation , Neoplasm Grading , Ovarian Neoplasms/pathology , Promoter Regions, Genetic , Transcriptome , Tumor Suppressor Protein p53/genetics , Exome Sequencing
15.
Breast Cancer Res Treat ; 171(1): 161-171, 2018 Aug.
Article En | MEDLINE | ID: mdl-29737472

PURPOSE: An increasing number of long intergenic non-coding RNAs (lincRNAs) appear to play critical roles in cancer development and progression. To assess the association between SNPs that reside in regions of lincRNAs and breast cancer risk, we performed a large case-control study in China. METHODS: We carried out a two-stage case-control study including 2881 breast cancer cases and 3220 controls. In stage I, we genotyped 17 independent (r2 < 0.5) SNPs located in 6 tumor-related lincRNAs by using the TaqMan platform. In stage II, SNPs potentially associated with breast cancer risk were replicated in an independent population. Quantitative real-time PCR was used to measure H19 levels in tissues from 228 breast cancer patients with different genotypes. RESULTS: We identified 2 SNPs significantly associated with breast cancer risk in stage I (P < 0.05), but not significantly replicated in stage II. We combined the data from stage I and stage II, and found that, compared with the rs2071095 CC genotype, AA and CA + AA genotypes were associated with significantly decreased risk of breast cancer (adjusted OR 0.83, 95% CI 0.69-0.99; adjusted OR 0.88, 95% CI 0.80-0.98, respectively). Stratified analyses showed that rs2071095 was associated with breast cancer risk in estrogen receptor (ER)-positive patients (P = 0.002), but not in ER-negative ones (P = 0.332). Expression levels of H19 in breast cancer cases with AA genotype were significantly lower than those with CC genotype. CONCLUSIONS: We identified that rs2071095 may contribute to the susceptibility of breast cancer in Chinese women via affecting H19 expression. The mechanisms underlying the association remain to be investigated.


Alleles , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Polymorphism, Single Nucleotide , RNA, Long Noncoding/genetics , Adult , Aged , Breast Neoplasms/pathology , Case-Control Studies , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Genotype , Humans , Middle Aged , Neoplasm Staging , Odds Ratio , Risk Factors
16.
Nanoscale ; 9(45): 17688-17693, 2017 Nov 23.
Article En | MEDLINE | ID: mdl-29119991

Ordered self-assembled arrays or superstructures of nanocrystals (NCs) have attracted intense research interest due to their ability to translate valuable nanoscale properties to larger length scales. Numerous techniques have been explored to induce self-assembly into various superstructures. Here we investigated a simple kinetic approach to form self-assembled one-dimensional perovskite CsPbX3 (X: halides) nanocrystal arrays templated inside a pod shaped inert lead sulfate (PbSO4) scaffold. Both the solvent effects, and the self-assembly process and mechanism, are systematically studied based on a uniform procedure developed to generate CsPbX3 nanocrystal superlattices with different sizes and compositions. The formation of one-dimensional (1D) chains of NCs within a half-cylindrical pod of PbSO4 reflects a balance between solvophobicity and solvophilicity of the components. By reducing the size of NCs, we successfully realized 2D superlattices with two or three rows of close-packed CsPbBr3 NCs, in addition to single string-of-pearl type 1D assemblies. The superlattices can be assembled both inside and outside of the half-cylindrical shells by regulating the reaction conditions. The self-assembly behavior is reminiscent of the host-guest systems of organic molecular species where supramolecular recognition rules apply to give well-defined complexes. The current study opens a door for controlling self-assembled nanostructures of CsPbX3 NCs, and provides an attainable platform for future optoelectronic devices.

17.
Appl Microbiol Biotechnol ; 101(16): 6473-6481, 2017 Aug.
Article En | MEDLINE | ID: mdl-28707067

Bacterial biofilms play an important role in chronic infections due to high-level tolerance to antibiotics. Thus, it is important to eradicate bacterial cells that are attached to implanted medical devices of different materials. Phagocytosis is a key process of the innate immunity to eliminate invading pathogens. Previous research demonstrated that the efficiency of phagocytosis is affected by the aspect ratio of polymer beads. Recently, we reported that the stiffness of polydimethylsiloxane (PDMS) influences Escherichia coli biofilm formation and the biofilm cells on stiff (5:1) PDMS are 46.2% shorter than those on soft (40:1) PDMS. Based on these findings, we hypothesized that E. coli cells attached on stiff PDMS can be more effectively removed via phagocytosis. This hypothesis was tested in the present study using viability assays, flow cytometry, and cell tracking. The results revealed that shorter E. coli cells detached from stiff PDMS were easier to be phagocytized than the longer cells from soft PDMS surfaces. Furthermore, macrophage cells were found to be more motile on stiff PDMS surfaces and more effective at phagocytosis of E. coli cells attached on these surfaces. These results may help the design of better biomaterials to reduce fouling and associated infections.


Biofilms/growth & development , Escherichia coli/physiology , Phagocytosis , Anti-Bacterial Agents/pharmacology , Bacterial Adhesion , Biofilms/drug effects , Dimethylpolysiloxanes/chemistry , Escherichia coli/drug effects , Humans , Macrophages/microbiology , Microbial Viability , Surface Properties , U937 Cells
18.
Medicine (Baltimore) ; 96(11): e6099, 2017 Mar.
Article En | MEDLINE | ID: mdl-28296723

RATIONALE: Bacterial meningitis (BM) has been recognized as a rare complication of spinal surgery. However, there are few reports on the management of postoperative BM in patients who have undergone spinal surgery. The initial approach to the treatment of patients suspected with acute BM depends on the stage at which the syndrome is recognized, the speed of the diagnostic evaluation, and the need for antimicrobial and adjunctive therapy. PATIENT CONCERNS: Here, we report the case of a patient with lumbar spinal stenosis and underwent a transforaminal lumbar interbody fusion at L4-L5. The dura mater was damaged intraoperatively. After the surgery, the patient displayed dizziness and vomiting. A CSF culture revealed Pseudomonas aeruginosa infection. DIAGNOSES: The patient was diagnosed with postoperative BM. INTERVENTIONS: Antibiotic was administered intravenously depends on the organism isolated. Nevertheless, the patient's clinical condition continued to deteriorate. The patient underwent 2 open revision surgeries for dural lacerations and cyst debridement repair. OUTCOMES: The patient's mental status returned to normal and her headaches diminished. The patient did not have fever and the infection healed. LESSONS: Surgical intervention is an effective method to treat BM after spinal operation in cases where conservative treatments have failed. Further, early surgical repair of dural lacerations and cyst debridement can be a treatment option for selected BM patients with complications including pseudomeningocele, wound infection, or cerebrospinal fluid leakage.


Lumbar Vertebrae/surgery , Meningitis, Bacterial/surgery , Postoperative Complications/surgery , Spinal Fusion/adverse effects , Spinal Stenosis/surgery , Female , Humans , Middle Aged , Postoperative Complications/etiology
19.
Eur J Med Res ; 22(1): 12, 2017 Mar 28.
Article En | MEDLINE | ID: mdl-28351415

OBJECTIVE: To investigate the effect of carbonyl sulfide (COS) on limb ischemia/reperfusion (I/R)-induced acute lung injury (ALI) and the associated mechanism in rats. METHODS: ALI was induced by bilateral hind limb I/R in Sprague-Dawley (SD) rats. Sixty-four SD rats were randomly divided into the control group, I/R group, I/R + COS group, and I/R + AIR group. We observed the survival rate of the rats and the morphological changes of lung tissues, and we measured the change in the lung coefficient, the expression levels of the intercellular adhesion factor-1 (ICAM-1) protein in lung tissue, the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-lß, and interleukin (IL)-6 in both lung tissue and serum, and cell apoptosis. RESULTS: Limb I/R caused significant lung tissue damage. The number of polymorphonuclear neutrophil in alveolar septa, the expression level of the ICAM-1 protein in lung tissue, the expression levels of TNF-α, IL-1, and IL-6 in lung tissue and serum, the lung coefficient, and cell apoptosis all increased. When a low dose of COS gas was administered prior to limb I/R, the variation of the above indicators was significantly reduced, while an increase in the dose of COS did not reduce the lung injury but rather increased the mortality rate. CONCLUSION: Carbonyl sulfide is another new gaseous signaling molecule, and a low dose of exogenous COS may play a protective role in I/R-induced ALI by acting as an anti-inflammatory agent by promoting the production of antioxidants and by inhibiting the expression of adhesion molecule proteins.


Acute Lung Injury/drug therapy , Reperfusion Injury/drug therapy , Sulfur Oxides/administration & dosage , Acute Lung Injury/genetics , Acute Lung Injury/physiopathology , Animals , Apoptosis/drug effects , Cell Adhesion Molecules/genetics , Extremities/injuries , Extremities/physiopathology , Humans , Interleukin-6/genetics , Male , Neutrophils/drug effects , Neutrophils/pathology , Rats , Reperfusion Injury/physiopathology , Tumor Necrosis Factor-alpha/genetics
20.
Chin J Traumatol ; 19(4): 193-8, 2016 08 01.
Article En | MEDLINE | ID: mdl-27578373

PURPOSE: To assess the effects of lipopolysaccharide (LPS) pretreatment on wound infection mouse model and evaluate the biological safety of the optimal pretreatment dose in vivo. METHODS: Mice were pretreated with LPS of different doses at 48 and 24 h before femoral medial lon- gitudinal incision was made and infected with different bacteria. RESULTS: It is showed that 0.5 mg/kg/time of LPS pretreatment can significantly alleviate the inflammation in mouse model infected with methicillin-resistances Staphylococcus aureus, methicillin-sensitive S. aureus, Pseudomonas aeruginosa,or Escherichia coli compared with doses of 0.25 mg/kg/time, 1 mg/ kg/time, and 1.5 mg/kg/time. CONCLUSIONS: LPS pretreatment can alleviate the inflammation in mouse model and the optimal dose is 0.5 mg/kg/time, and meanwhile it does not damage organs' function.


Inflammation/prevention & control , Lipopolysaccharides/therapeutic use , Surgical Wound Infection/drug therapy , Animals , Disease Models, Animal , Female , Mice , Mice, Inbred BALB C , Toll-Like Receptor 4/physiology
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