Diurnal oscillations of epigenetic modifications are associated with variation in rhythmic expression of homoeologous genes in Brassica napus.

BACKGROUND: Epigenetic modifications that exhibit circadian oscillations also promote circadian oscillations of gene expression. Brassica napus is a heterozygous polyploid species that has undergone distant hybridization and genome doubling events and has a young and distinct species origin. Studies incorporating circadian rhythm analysis of epigenetic modifications can offer new insights into differences in diurnal oscillation behavior among subgenomes and the regulation of diverse expressions of homologous gene rhythms in biological clocks. RESULTS: In this study, we created a high-resolution and multioscillatory gene expression dataset, active histone modification (H3K4me3, H3K9ac), and RNAPII recruitment in Brassica napus. We also conducted the pioneering characterization of the diurnal rhythm of transcription and epigenetic modifications in an allopolyploid species. We compared the evolution of diurnal rhythms between subgenomes and observed that the Cn subgenome had higher diurnal oscillation activity in both transcription and active histone modifications than the An subgenome. Compared to the A subgenome in Brassica rapa, the An subgenome of Brassica napus displayed significant changes in diurnal oscillation characteristics of transcription. Homologous gene pairs exhibited a higher proportion of diurnal oscillation in transcription than subgenome-specific genes, attributed to higher chromatin accessibility and abundance of active epigenetic modification types. We found that the diurnal expression of homologous genes displayed diversity, and the redundancy of the circadian system resulted in extensive changes in the diurnal rhythm characteristics of clock genes after distant hybridization and genome duplication events. Epigenetic modifications influenced the differences in the diurnal rhythm of homologous gene expression, and the diurnal oscillation of homologous gene expression was affected by the combination of multiple histone modifications. CONCLUSIONS: Herein, we presented, for the first time, a characterization of the diurnal rhythm characteristics of gene expression and its epigenetic modifications in an allopolyploid species. Our discoveries shed light on the epigenetic factors responsible for the diurnal oscillation activity imbalance between subgenomes and homologous genes' rhythmic expression differences. The comprehensive time-series dataset we generated for gene expression and epigenetic modifications provides a valuable resource for future investigations into the regulatory mechanisms of protein-coding genes in Brassica napus.

Optimization of Cu/Sn Alloy Sputtering Process Based on Orthogonal Experimental Design Method.

The performance of supercapacitors is directly influenced by the conductivity of polypyrrole, which serves as the electrode material. In order to balance considerations of cost-effectiveness and conductivity, this study employs magnetron sputtering to fabricate a copper-tin alloy layer as the conductive layer for polypyrrole. The deposition of a copper-tin alloy film through magnetron sputtering has a significant impact on the polymerization effect of pyrrole as well as being a crucial factor influencing the performance of supercapacitors. Various parameters, including working pressure, sputtering time, and sputtering power, affect the conductivity of the copper-tin alloy film. Furthermore, the degree of influence of each parameter on the conductivity of the copper-tin alloy film varies. This study utilizes an orthogonal experimental design to investigate the impact of various factors and levels on the conductivity and uniformity of a metal film. The objective is to optimize the process parameters for the creation of a copper-tin alloy film with desirable characteristics. Experimental results indicate that the working voltage, sputtering time, and sputtering power significantly influence the coefficient of variation, deposition rate, target current, and operating voltage of the film. Furthermore, FT-IR, XRD, and SEM tests are conducted on samples prepared using the identified optimal process parameters. In addition, we demonstrate various approaches to enhance the experiment's reliability. The findings indicate that the most favorable process parameters for achieving optimal results are a working pressure of 0.065 Pa, a sputtering time of 20 min, and a sputtering power of 70 W. It was observed that the sputtering time significantly influences the uniformity of the copper-tin alloy film, whereas the sputtering power has a minimal impact on its uniformity. The deposition rate is primarily influenced by the working pressure, with the greatest effect observed. Conversely, the sputtering time has the least impact on the deposition rate. Similarly, the target current is predominantly affected by the sputtering power, exhibiting the greatest influence, while the sputtering time has the least effect. Furthermore, the working voltage is most significantly influenced by the working pressure, whereas the sputtering time has the least impact on the working voltage.

Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes.

Studies on the lung cancer genome are indispensable for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, dysregulation of long-range chromatin interactions in lung cancer remains poorly described. To better understand the three-dimensional (3D) genomic interaction features of the lung cancer genome, we used the A549 cell line as a model system and generated high-resolution chromatin interactions associated with RNA polymerase II (RNAPII), CCCTC-binding factor (CTCF), enhancer of zeste homolog 2 (EZH2), and histone 3 lysine 27 trimethylation (H3K27me3) using long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET). Analysis showed that EZH2/H3K27me3-mediated interactions further repressed target genes, either through loops or domains, and their distributions along the genome were distinct from and complementary to those associated with RNAPII. Cancer-related genes were highly enriched with chromatin interactions, and chromatin interactions specific to the A549 cell line were associated with oncogenes and tumor suppressor genes, such as additional repressive interactions on FOXO4 and promoter-promoter interactions between NF1 and RNF135. Knockout of an anchor associated with chromatin interactions reversed the dysregulation of cancer-related genes, suggesting that chromatin interactions are essential for proper expression of lung cancer-related genes. These findings demonstrate the 3D landscape and gene regulatory relationships of the lung cancer genome.

Clinical Outcomes of Treatment Strategies for Postoperative Plate Fracture and In Situ Fracture of the Femoral Shaft.

Objective: To investigate the treatment and clinical efficacy of postoperative plate fracture and in situ fracture of the femoral stem. Methods: We have retrospectively analyzed the clinical data, revised surgery information, and clinical efficacy of patients with postoperative plate fracture of the femoral stem in our hospital. A total of 33 cases were included whose original fractures were located in the upper and cadaveric femur and treated with paralleling intramedullary pins for revision surgery, as well as patients whose original fractures were located in the lower femur which were fixed with retrograde intramedullary nailing or anatomical locking and compression splints in the distal femur. For the selection of bone grafting, the original fracture site with Fernadez-Esteve scab grades I and II was treated with an autologous iliac bone graft. Postoperatively, patients were evaluated for fracture healing time, the clinical outcome of the affected limb, and complications in the iliac bone donor area. Results: All patients were followed up until fracture healing, and all patients achieved clinical healing with a healing rate of 100% and a mean healing time of 6.3 months. No internal fixation failure such as rebreakage or loosening of the internal fixation occurred in all patients during the follow-up period. According to the Tohner-Wrnch criteria, 23 cases were excellent, 10 cases were good, and 0 cases were poor, with an excellent rate of 100%. Complications in the autologous iliac bone donor area amounted to 36.7%. Conclusion: For patients with original fractures located in the upper femoral segment or cadre, it is recommended to perform revision surgery with a paralleling intramedullary pin, while patients with original fractures located in the lower femoral segment are fixed with the retrograde intramedullary nailing or an anatomical type of distal femoral locking and compression splint. Patients with postoperative plate fractures of the femoral stem do not require routine autologous bone grafting for revision surgery.

A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity.

ARID4A plays an important role in regulating gene expression and cell proliferation. ARID4A belongs to the AT-rich interaction domain (ARID)-containing family, and a PWWP domain immediately precedes its ARID region. The molecular mechanism and structural basis of ARID4A are largely unknown. Whole-exome sequencing (WES) revealed that a novel heterozygous missense variant, ARID4A c.1231 C > G (p.His411Asp), was associated with schizophrenia (SCZ) in this study. We determined the crystal structure of the PWWP-ARID tandem at 2.05 Å, revealing an unexpected mode in which ARID4A assembles with its PWWP and ARID from a structural and functional supramodule. Our results further showed that compared with the wild type, the p.His411Asp ARID mutant protein adopts a less compact conformation and exhibits a weaker dsDNA-binding ability. The p.His411Asp mutation decreased the number of cells that were arrested in the G0-G1 phase and caused more cells to progress to the G2-M phase. In addition, the missense mutation promoted the proliferation of HEK293T cells. In conclusion, our data provide evidence that ARID4A p.His411Asp could cause a conformational change in the ARID4A ARID domain, influence the DNA binding function, and subsequently disturb the cell cycle arrest in the G1 phase. ARID4A is likely a susceptibility gene for SCZ; thus, these findings provide new insight into the role of ARID4A in psychiatric disorders.

Can virtual touch tissue imaging quantification be a reliable method to detect anterior talofibular ligament type I injury at the acute, subacute, and chronic stages?

BACKGROUND: Anterior talofibular ligament (ATFL) injury affects ankle joint stability. To date, very few studies have examined tissue stiffness changes inside injured ligaments. Virtual touch tissue imaging quantification (VTIQ) allows for the non-invasive quantitative measurement of tissue stiffness. The present study aimed to examine the efficacy of VTIQ as a method for detecting ligament injury. METHODS: A total of 206 patients diagnosed with unilateral ATFL type I injury (81 acute cases, 69 subacute cases, and 56 chronic cases) were reviewed retrospectively. Shear wave velocity (SWV) values were collected from both the injured and non-affected sides of the ATFL using a virtual touch tissue imaging quantification technique (ACUSON Oxana 2, Siemens Medical Solutions USA, Inc.). RESULTS: The average SWV of injured ATFL was 4.09±1.15 m/s in the acute group, 5.60±1.39 m/s in the subacute group, and 7.74±1.44 m/s in the chronic group (P<0.001). The SWV values of the ATFL on the non-affected side were almost identical (acute 7.50±1.12 m/s, subacute 7.53±1.06 m/s, and chronic 7.61±1.30 m/s; P>0.05). The injured ATFL had a significantly lower SWV value than the non-affected ATFL in the acute and subacute groups (P<0.001); however, there was no significant difference in the chronic group (P>0.05). Concerning the validity of SWV as a predictor of acute and subacute ATFL injury, the receiver operator characteristics curve analysis showed that the best cut-off point for SWV was 6.165 m/s, with 84.3% sensitivity, 88.5% specificity, and an area under the curve of 0.93 (95% CI, 0.90-0.95). CONCLUSIONS: VTIQ is a reliable sonographic method for detecting acute and subacute ATFL type I injury.

Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth.

Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.

OsMLH1 interacts with OsMLH3 to regulate synapsis and interference-sensitive crossover formation during meiosis in rice.

Meiotic recombination is essential for reciprocal exchange of genetic information between homologous chromosomes and their subsequent proper segregation in sexually reproducing organisms. MLH1 and MLH3 belong to meiosis-specific members of the MutL-homolog family, which are required for normal level of crossovers (COs) in some eukaryotes. However, their functions in plants need to be further elucidated. Here, we report the identification of OsMLH1 and reveal its functions during meiosis in rice. Using CRISPR-Cas9 approach, two independent mutants, Osmlh1-1 and Osmlh1-2, are generated and exhibited significantly reduced male fertility. In Osmlh1-1, the clearance of PAIR2 is delayed and partial ZEP1 proteins are not loaded into the chromosomes, which might be due to the deficient in resolution of interlocks at late zygotene. Thus, OsMLH1 is required for the assembly of synapsis complex. In Osmlh1-1, CO number is dropped by ~53% and the distribution of residual COs is consistent with predicted Poisson distribution, indicating that OsMLH1 is essential for the formation of interference-sensitive COs (class I COs). OsMLH1 interacts with OsMLH3 through their C-terminal domains. Mutation in OsMLH3 also affects the pollen fertility. Thus, our experiments reveal that the conserved heterodimer MutLγ (OsMLH1-OsMLH3) is essential for the formation of class I COs in rice.

Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study.

BACKGROUND: Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN). METHODS: A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC). RESULTS: The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10-8). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10-8) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis. CONCLUSIONS: The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments.

Asymmetric epigenome maps of subgenomes reveal imbalanced transcription and distinct evolutionary trends in Brassica napus.

The complexity of the epigenome landscape and transcriptional regulation is significantly increased during plant polyploidization, which drives genome evolution and contributes to the increased adaptability to diverse environments. However, a comprehensive epigenome map of Brassica napus is still unavailable. In this study, we performed integrative analysis of five histone modifications, RNA polymerase II occupancy, DNA methylation, and transcriptomes in two B. napus lines (2063A and B409), and established global maps of regulatory elements, chromatin states, and their dynamics for the whole genome (including the An and Cn subgenomes) in four tissue types (young leaf, flower bud, silique, and root) of these two lines. Approximately 65.8% of the genome was annotated with different epigenomic signals. Compared with the Cn subgenome, the An subgenome possesses a higher level of active epigenetic marks and lower level of repressive epigenetic marks. Genes from subgenome-unique regions contribute to the major differences between the An and Cn subgenomes. Asymmetric histone modifications between homeologous gene pairs reflect their biased expression patterns. We identified a novel bivalent chromatin state (with H3K4me1 and H3K27me3) in B. napus that is associated with tissue-specific gene expression. Furthermore, we observed that different types of duplicated genes have discrepant patterns of histone modification and DNA methylation levels. Collectively, our findings provide a valuable epigenetic resource for allopolyploid plants.

Bibliometric analysis of randomized controlled trials of colorectal cancer over the last decade.

BACKGROUND: Colorectal cancer is one of the most common cancers globally. In China, its prevalence ranks fourth and fifth among females and males, respectively. Presently, treatment of rectal cancer follows a multidisciplinary comprehensive treatment approach involving surgery, radiotherapy, chemotherapy, and targeted therapy. With deepening theoretical and molecular research on colorectal cancer, randomized controlled trials (RCTs) on colorectal cancer have made significant progress. However, many RCTs have shortfalls. AIM: To investigate the RCTs of global colorectal cancer spanning from 2008 to 2018. To provide suggestions for conducting Chinese RCTs of colorectal cancer. METHODS: PubMed and Web of Science databases were searched to obtain RCTs of colorectal cancer carried out between January 1, 2008, and January 1, 2018. The bibliometric method was used for statistical analysis of the publication years, countries/regions, authors, institutions, source journals, quoted times, key words, and authors. RESULTS: Colorectal cancer RCTs showed an upward trend between 2008 to 2018; the top 10 research institutions in the included literature were from the United States, the United Kingdom, and other countries with a high incidence of colorectal cancer. Most of the related research journals are sponsored by European and American countries. The 15 most cited studies involved international multicenter clinical research, having few participants from Chinese research institutions. Network visualization using key words showed that RCTs on colorectal cancer focus on screening, disease-free survival, drug treatment, surgical methods, clinical trials, quality of life, and prognosis. The result of the coauthorship network analysis showed that Chinese researchers are less involved in international exchanges compared to those from leading publication countries. CONCLUSION: High-quality RCTs are increasingly favored by leading international journals. However, there is still a large gap in clinical research between China and leading countries. Researchers should implement standardized and accurate clinical trials, strengthen international multicenter cooperation, and emphasize quality control.

A Novel Coronavirus from Patients with Pneumonia in China, 2019.

In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

MiR-145: a potential biomarker of cancer migration and invasion.

MircoRNAs (miRNAs) are a diverse family of highly-conserved small non-coding RNAs, which range from approximately 18 to 25 nucleotides in size. They regulate gene expression transcriptionally or post-transcriptionally via binding to the 3'-untranslated region (3'-UTR) of target message RNAs (mRNAs). MiRNAs have emerged as molecular regulators that participate in physiological and pathological processes of diverse malignancies. Among them, miRNA-145 (miR-145) played a profound role in tumorigenesis and progression of various neoplasms. In this review, we summarized the recent findings regarding miR-145, to elucidate its functional roles in cell invasion and migration of diverse human malignancies, and considered it a potential biomarker for cancer diagnosis, screening, and prognosis.

Short-term efficacy of transvaginal specimen extraction for right colon cancer based on propensity score matching: A retrospective cohort study.

BACKGROUND: Recently, the incidence of colorectal cancer has increased each year. Natural orifice specimen extraction surgery (NOSES) removes the specimen from a natural cavity of the human body (anal or vaginal) and completes reconstruction of the digestive tract. There are only a few trocar scars in the abdomen after surgery. Transvaginal specimen extraction for right-sided colon cancer is one of the classic NOSES surgeries. As NOSES is accepted by increasing numbers of colorectal surgeons, NOSES technology is becoming increasingly widely used in China and abroad. Studies have confirmed the feasibility and safety of NOSES. Therefore, it is necessary to conduct further clinical studies to evaluate the short-term efficacy of the NOSES procedure. OBJECTIVE: To investigate the short-term efficacy of transvaginal specimens for laparoscopic right colon cancer (NOSES). METHODS: We conducted a retrospective analysis of 90 cases of laparoscopic right colon cancer radical surgery performed continuously in the anorectal surgery of our Hospital from June 2015 to December 2018. Thirty-two patients underwent complete laparoscopic anastomosis and transvaginal specimen removal (NOSES group), and 58 patients underwent conventional abdominal wall removal specimen surgery (LAP group). The general data of the patients were matched by the propensity score matching (PSM) method 1:1. Thirty-one pairs of cases were successfully matched, and the intraoperative and postoperative data were analysed. RESULTS: After PSM, the baseline data were balanced between the two groups. A total of 62 patients in the two groups were successfully operated without conversion. There were no significant differences in intraoperative blood loss, lymph node dissection, sputum tumour cell positive rate, bacterial culture positive rate, postoperative follow-up and postoperative pelvic floor function evaluation (P > 0.05). Neither tumour cells nor bacteria were detected in the rinse solution at the start of the operation. Compared with the LAP group, the incidence of postoperative complications was lower in the NOSES group (6.4% vs. 29.0%, P = 0.006), and the gastrointestinal function recovery time was shorter (2.58 ±â€¯0.92 vs. 3.42 ±â€¯0.92, P = 0.001), postoperative hospital stay was shorter (6.68 ±â€¯1.47 vs. 9.58 ±â€¯2.22, P < 0.001), postoperative pain score was lower (postoperative day 1: 2.35 ±â€¯1.52 vs. 4.87 ±â€¯1.50; postoperative day 3: 1.81 ±â€¯1.11 vs. 4.00 ±â€¯1.18; postoperative day 5: 1.45 ±â€¯1.00 vs. 2.97 ±â€¯1.17; P < 0.001), additional analgesic drug use rate was lower (12.9% vs. 61.3%, P < 0.001), and patients were more satisfied with the appearance of the abdominal wall after surgery (100% vs. 23.6%, P < 0.001). CONCLUSION: This study used PSM to remove confounding factors and retrospectively analysed the short-term efficacy of transvaginal specimens for laparoscopic right colon cancer radical resection. The results showed that the laparoscopic right colon cancer radical resection was satisfactory, ensuring sterility. At the same time, there is a clear advantage in reducing postoperative pain, shortening postoperative hospital stays, reducing the incidence of postoperative complications, and improving the appearance of the abdominal wall.

MiR-27a: A Novel Biomarker and Potential Therapeutic Target in Tumors.

MicroRNAs (miRNAs) are endogenous, time sequencing, conserved and small non-coding RNA molecules (19-25 bp long) that regulate gene expression at the post-transcriptional level by binding to the partial sequence homology of the 3'-untranslated region of target messenger (m)RNA. The miRNA-27 family consists of miR-27a and miR-27b, which are transcribed from different chromosomes and different in nucleotide at the 3' end. It has been reported that miR-27a was located on chromosome 19 and played a vital role in tumor development. Increasing evidences support a vital role for miR-27a in modulating polymorphisms, tumorigenesis, proliferation, apoptosis, invasion, migration and angiogenesis. Apart from it, miR-27a could affect drug sensitivity, treatment of cancer and patients prognosis. The miR-27a could be an oncogene or a tumor suppressor in several types of cancer, including colon cancer, pancreatic cancer, breast cancer, bladder cancer and hepatocellular carcinoma. In this review, we discuss the role of miR-27a in tumor biology and clinical significance in detail and offer novel insights into molecular targeting therapy for human cancers.

Short-term efficacy of natural orifice specimen extraction surgery for low rectal cancer.

BACKGROUND: This case-control study compared the short-term clinical efficacy of natural orifice specimen extraction surgery (NOSES) using a prolapsing technique and the conventional laparoscopic-assisted approach for low rectal cancer. AIM: To further explore the application value of the transanal placement of the anvil and to evaluate the short-term efficacy of NOSES for resecting specimens of low rectal cancer, as well as to provide a theoretical basis for its extensive clinical application. METHODS: From June 2015 to June 2018, 108 consecutive laparoscopic-assisted low rectal cancer resections were performed at our center. Among them, 26 specimens were resected transanally using a prolapsing technique (NOSES), and 82 specimens were resected through a conventional abdominal wall small incision (LAP). A propensity score matching method was used to select 26 pairs of matched patients, and their perioperative data were analyzed. RESULTS: The baseline data were comparable between the two matched groups. All 52 patients underwent the surgery successfully. The operative time, blood loss, number of harvested lymph nodes, postoperative complication rate, circumferential margin involvement, postoperative follow-up data, and postoperative anal function were not statistically significant. The NOSES group had shorter time to gastrointestinal function recovery (2.6 ± 1.0 d vs 3.4 ± 0.9 d, P = 0.006), shorter postoperative hospital stay (7.1 ± 1.7 d vs 8.3 ± 1.1 d, P = 0.003), lower pain score (day 1: 2.7 ± 1.8 vs 4.6 ± 1.9, day 3: 2.0 ± 1.1 vs 4.1 ± 1.2, day 5: 1.7 ± 0.9 vs 3.3 ± 1.0, P < 0.001), a lower rate of additional analgesic use (11.5% vs 61.5%, P = 0.001), and a higher satisfaction rate in terms of the aesthetic appearance of the abdominal wall after surgery (100% vs 23.1%, P < 0.001). CONCLUSION: NOSES for low rectal cancer can achieve satisfactory short-term efficacy and has advantages in reducing postoperative pain, shortening the length of postoperative hospital stay, and improving patients' satisfaction in terms of a more aesthetic appearance of the abdominal wall.

Prussian blue-modified ferritin nanoparticles for effective tumor chemo-photothermal combination therapy via enhancing reactive oxygen species production.

To realize the photothermal therapy ability of Prussian blue-modified ferritin nanoparticles (PB-Ft NPs) and its synergistic effect with chemotherapy, PB-Ft NPs were synthesized by a simple surface double decomposition reaction. Mean sizes of ferritin and PB-Ft NPs were 10.4 nm and 12.6 nm, respectively. The obtained PB-Ft NPs were verified to have both the photothermal conversion ability of Prussian blue and the morphology of ferritin. The in vitro and in vivo photothermal therapy results confirm PB-Ft NPs can successfully inhibit the growth of murine breast cancer cell line (4T1) without any obvious side effect. Moreover, taking use of the peroxidase-like activity of PB-Ft NPs, the photothermal therapy effect of PB-Ft NPs effectively improved the curative effect of gemcitabine (GEM) via enhancing reactive oxygen species production. The obtained PB-Ft NPs can be served as a useful and safe photothermal therapy agent in breast cancer. Moreover, PB-Ft NPs-assisted photothermal therapy can be applied as an adjunctive therapy with various established cancer treatments such as chemotherapy.

EZH2 contributes to 5-FU resistance in gastric cancer by epigenetically suppressing FBXO32 expression.

BACKGROUND: Increasing evidence suggests the involvement of enhancer of zeste homologue 2 (EZH2) in chemoresistance of cancer treatment. Nevertheless, its function and molecular mechanisms in gastric cancer (GC) chemoresistance are still not well elucidated. MATERIALS AND METHODS: In the present study, we investigated the functional role of EZH2 in 5-fluorouracil (5-FU) resistance of GC cells and discovered the underlying molecular mechanism. RESULTS: Results revealed that EZH2 was upregulated in 5-FU-resistant GC tissues and cell lines. High ZEH2 expression was correlated with poor prognosis of GC patients. EZH2 knockdown enhanced 5-FU sensitivity of AGS/5-FU and SGC-7901/5-FU cells. Moreover, EZH2 could epigenetically suppress FBXO32 expression. FBXO32 overexpression could mimic the functional role of downregulated EZH2 in 5-FU resistance. FBXO32 knockdown counteracted the inductive effect of EZH2 inhibition on 5-FU sensitivity of AGS/5-FU and SGC-7901/5-FU cells. Furthermore, EZH2 knockdown facilitated 5-FU sensitivity of 5-FU-resistant GC cells in vivo. CONCLUSION: In summary, EZH2 depletion overcame 5-FU resistance in GC by epigenetically silencing FBXO32, providing a novel therapeutic target for GC chemoresistance.

[Application of improved anvil placement in laparoscopic resection of low rectal cancer with resection of anal eversion].

OBJECTIVE: To investigate the feasibility and application value of improved anvil placement in laparoscopic resection of low rectal cancer with resection of anal eversion. METHODS: A retrospective study was performed on 17 patients who were operated by improved extracorporeal anvil placement in laparoscopic resection of low rectal cancer with resection of anal eversion at Huaihe Hospital of Henan University during June 2015 and June 2017. INCLUSION CRITERIA: (1) distance from tumor low margin to anal edge was 4 to 6 cm; (2) protrusive type tumor with a circumferential diameter of less than 3 cm; (3) ulcer type tumor with circumferential bowel infiltration of less than 1/2; (4) no distant metastasis(M0) and preoperative MRI of pelvic floor indicating T1-3N0. Patients with BMI>35 kg/m2, or insufficient length of sigmoid and mesentery, or thickening sigmoid and mesentery were excluded. According to total mesorectal excision(TME) principle, rectum and its mesentery was resected completely; the sigmoid colon was cut off at the superior margin of tumor; the oval forceps was placed through anus to clamp and evert the rectum out of the anus; the rectum was transected at 1-2 cm from the lower edge of the tumor; the distal sigmoid colon was pulled out through anus; purse string suture was made after insertion of anvil and was restored to the abdominal cavity; end-to-end anastomosis of the rectum and sigmoid colon was performed after closing rectal stump. RESULTS: Of 17 low rectal cancer patients, 10 were male and 7 were female with age of 42 to 71 (median 58) years old and BMI of 20.6 to 33.5(median 26) kg/m2. Preoperative staging indicated 2 cases of stage I, 15 cases of stage II. Distance from tumor low margin to anal edge was 4 to 6(median 5.0) cm and diameter of tumor was 3.4 to 4.8 (median 4.2) cm. All the patients completed operations successfully without conversion to laparotomy. The operation time was 124 to 182 (median 136) minutes. Distal sigmoid colon was difficult to pull out in 1 patient due to the insufficient free of the mesosigmoid, which was then successful after the mesosigmoid was dissociated with laparoscopy thoroughly again. The intraoperative blood loss was 10 to 50 (median 20) ml. Postoperative pathology reveled 2 cases of stage I, 12 cases of stageII and 3 cases of stage III; 1 case of poorly differentiated adenocarcinoma, 15 cases of moderately differentiated adenocarcinoma and 1 case of highly differentiated adenocarcinoma. The postoperative exhaust time was 24 to 128 (median 36) hours and hospital stay was 5 to 15 (median 8) days. No anastomotic leakage and intra-abdominal infection was found. Fifteen patients were followed up for 5 to 24 months without local recurrence or distant metastasis. CONCLUSION: The improved anvil placement in laparoscopic resection of low rectal cancer with resection of anal eversion without abdominal incision is safe and feasible.

The Energetics and Physiological Impact of Cohesin Extrusion.

Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA. We also identify architectural "stripes," where a loop anchor interacts with entire domains at high frequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitate Igh transcription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulate Igh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development.