RNA methylation, homologous recombination repair and therapeutic resistance.

Homologous recombination (HR) repair of DNA double-strand breaks (DSBs) is critical for maintaining genomic integrity and stability. Defects in HR increase the risk of tumorigenesis. However, many human tumors exhibit enhanced HR repair capabilities, consequently endowing tumor cells with resistance to DNA-damaging chemotherapy and radiotherapy. This review summarizes the role of RNA methylation in HR repair and therapeutic resistance in human tumors. We also analyzed the interactions between RNA methylation and other HR-modulating modifications including histone acetylation, histone deacetylation, ubiquitination, deubiquitination, protein arginine methylation, and gene transcription. This review proposes that targeting RNA methylation is a promising approach to overcoming HR-mediated therapeutic resistance.

Type IV pili are involved in phenotypes associated with Clostridioides difficile pathogenesis.

Clostridioides difficile is a Gram-positive, spore-forming, rod-shaped, obligate anaerobe that is the leading cause of antibiotic-associated diarrhea. Type IV pili (T4P) are elongated appendages on the surface of C. difficile that are polymerized from many pilin proteins. T4P play an important role in C. difficile adherence and particularly in its persistence in the host intestine. Recent studies have shown that T4P promote C. difficile aggregation, surface motility, and biofilm formation, which may enhance its pathogenicity. Additionally, the second messenger cyclic diguanylate increases pilA1 transcript abundance, indirectly promoting T4P-mediated aggregation, surface motility, and biofilm formation of C. difficile. This review summarizes recent advances in C. difficile T4P research and the physiological activities of T4P in the context of C. difficile pathogenesis.

Impact of pre-annealing process on electrical properties and stability of indium zinc oxide thin-film transistors.

This paper examined the effects of no treatment versus plasma treatment, and femtosecond laser irradiation as pre-annealing processes on indium zinc oxide (IZO) films and annealing at high temperatures. The plasma pre-annealed multilayer stacked IZO TFTs showed better electrical properties with mobility enhancement from 2.45 to 7.81 cm2/Vs, but exhibited diminished on-off current ratio (Ion/Ioff). The IZO thin-film transistor (TFT) prepared with femtosecond laser pre-annealing with low pulse energy generation (power of 3 W at 700 nm wavelength) for 100 s has also exhibited significantly improved electrical performance, the saturation mobility increased to 4.91 cm2/Vs, the Ion/Ioff ratio was enhanced from 4.5 × 105 to 2.1 × 106, the threshold voltage improved from - 1.44 to - 0.25 V, and the subthreshold swing was reduced from 1.21 to 0.61 V/dec. In conclusion, IZO TFTs with improved performance can be prepared using a femtosecond laser pre-annealing process, which has great potential for fabricating low-cost, high-performance devices.

An Improved Networked Predictive Controller for Vascular Robot Using 5G Networks.

Percutaneous coronary intervention (PCI) has gradually become the most common treatment of coronary artery disease (CAD) in clinical practice due to its advantages of small trauma and quick recovery. However, the availability of hospitals with cardiac catheterization facilities and trained interventionalists is extremely limited in remote and underdeveloped areas. Remote vascular robotic system can assist interventionalists to complete operations precisely, and reduce occupational health hazards occurrence. In this paper, a bionic remote vascular robot is introduced in detail from three parts: mechanism, communication architecture, and controller model. Firstly, human finger-like mechanisms in vascular robot enable the interventionalists to advance, retract and rotate the guidewires or balloons. Secondly, a 5G-based communication system is built to satisfy the end-to-end requirements of strong data transmission and packet priority setting in remote robot control. Thirdly, a generalized predictive controller (GPC) is developed to suppress the effect of time-varying network delay and parameter identification error, while adding a designed polynomial compensation module to reduce tracking error and improve system responsiveness. Then, the simulation experiment verifies the system performance in comparison with different algorithms, network delay, and packet loss rate. Finally, the improved control system conducted PCI on an experimental pig, which reduced the delivery integral absolute error (IAE) by at least 20% compared with traditional methods.

Design and Performance Evaluation of a Novel Vascular Robotic System for Complex Percutaneous Coronary Interventions.

The robotic-assisted percutaneous coronary intervention is an emerging technology with great potential to solve the shortcomings of existing treatments. However, the current robotic systems can not manipulate two guidewires or ballons/stents simultaneously for coronary bifurcation lesions. This paper presents VasCure, a novel bio-inspired vascular robotic system, to deliver two guidewires and stents into the main branch and side branch of bifurcation lesions in sequence. The system is designed in master-slave architecture to reduce occupational hazards of radiation exposure and orthopedic injury to interventional surgeons. The slave delivery device has one active roller and two passive rollers to manipulate two interventional devices. The performance of the VasCure was verified by in vitro and in vivo animal experiments. In vitro results showed the robotic system has good accuracy to deliver guidewires and the maximum error is 0.38mm. In an animal experiment, the interventional surgeon delivered two guidewires and balloons to the left circumflex branch and the left anterior descending branch of the pig, which confirmed the feasibility of the vascular robotic system.

Arbuscular mycorrhizal fungi regulate soil respiration and its response to precipitation change in a semiarid steppe.

Arbuscular mycorrhizal fungi (AMF) are critical links in plant-soil continuum and play a critical role in soil carbon cycles. Soil respiration, one of the largest carbon fluxes in global carbon cycle, is sensitive to precipitation change in semiarid ecosystems. In this study, a field experiment with fungicide application and water addition was conducted during 2010-2013 in a semiarid steppe in Inner Mongolia, China, and soil respiration was continuously measured to investigate the influences of AMF on soil respiration under different precipitation regimes. Results showed that soil respiration was promoted by water addition treatment especially during drought seasons, which induced a nonlinear response of soil respiration to precipitation change. Fungicide application suppressed AMF root colonization without impacts on soil microbes. AMF suppression treatment accelerated soil respiration with 2.7, 28.5 and 37.6 g C m(-2) across three seasons, which were mainly caused by the enhanced heterotrophic component. A steeper response of soil respiration rate to precipitation was found under fungicide application treatments, suggesting a greater dampening effect of AMF on soil carbon release as water availability increased. Our study highlighted the importance of AMF on soil carbon stabilization and sequestration in semiarid steppe ecosystems especially during wet seasons.

Primary closure following laparoscopic common bile duct exploration combined with intraoperative cholangiography and choledochoscopy.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) has become one of the main options for treating choledocholithiasis associated with cholelithiasis. Our objective was to assess the short-term outcomes of patients undergoing laparoscopic primary closure of the common bile duct (CBD) compared with laparoscopic choledochotomy plus T-tube drainage. METHODS: We retrospectively studied 137 patients undergoing primary closure following LCBDE (group A) compared with 102 cases with laparoscopic choledochotomy plus T-tube drainage (group B) between January 2007 and January 2010. Intraoperative cholangiography (IOC) and choledochoscopy were performed in all patients. RESULTS: Three patients in group A (2.2%) were converted to open surgery and two (2.0%) in group B because of serious adherence. According to routine IOC, unexpected CBD stones were found in 16 cases (6.8%). The duration of the operation in group A was shorter than in group B (92.4 ± 15.2 vs. 125.7± 32.6 min, P < 0.05), as was length of postoperative stay (3.1± 2.4 vs. 5.7± 4.3 days, P < 0.05). Postoperative bile leakage occurred in six patients (4.5%) in group A and four cases (4.0%) in group B; all of the patients recovered after simple drainage without reoperation. Bile peritonitis was seen in one case after T-tube removal. The median follow-up was 26 months. There were no recurrences. CONCLUSIONS: Laparoscopic primary closure of the CBD is safe and successful for the management of CBD stones. Application of IOC and choledochoscopy to ensure clearance of the CBD and careful suturing are essential for primary closure.

Aberrant methylation frequency of TNFRSF10C promoter in pancreatic cancer cell lines.

BACKGROUND: A growing body of evidence suggests that many tumors are initiated by both epigenetic abnormalities and gene mutations, which promote tumor progression. Epigenetic abnormalities include changes in DNA methylation and in the modification of histones. This study aimed to assess the status of methylation in the CpG island (CGI) of the tumor necrosis factor receptor superfamily member 10c (TNFRSF10C) with combined bisulfite restriction analysis (COBRA) and to evaluate its role in the progression of pancreatic cancer (PC). METHODS: The methylation status of four PC cell lines was assessed using COBRA and/or bisulfite genomic sequencing (BGS). Changes in methylation and TNFRSF10C expression in PC cell lines before and after treatment with 5-aza-2'-deoxycytidine (5-aza-dC) and/or trichostatin A (TSA) were assessed by BGS and real-time RT-PCR. Apoptosis in the four cell lines was tested by flow cytometry (FCM) and TUNEL assay. RESULTS: The methylation status of the TNFRSF10C promoter was assessed in PC cells (BxPC-3: 68.84+/-8.71%; CFPAC-1: 0; PANC-1: 96.77+/-4.57%; SW1990: 54.97+/-7.33%) with the COBRA assay, which was confirmed by the results of BGS. After treatment with 5-aza-dC and/or TSA, apoptosis was induced in PC cells to different degrees, and the levels of TNFRSF10C transcriptional expression in the PC cell lines (except CFPAC-1) increased markedly after 5-aza-dC treatment. CONCLUSIONS: A high frequency of CGI methylation in the TNFRSF10C promoter results in inactivation of the gene and enhancement of tumor growth in most PC cell lines (except CFPAC-1). Inactivation of TNFRSF10C by CGI hypermethylation can play an important role in PC progression and be potentially useful as a diagnostic marker and a new therapeutic approach for PC.

Endoscopic total parathyroidectomy and partial parathyroid tissue autotransplantation for patients with secondary hyperparathyroidism: a new surgical approach.

BACKGROUND: Secondary hyperparathyroidism (SHPT) (i.e., renal hyperparathyroidism) is one of the most serious complications in long-term hemodialysis patients. The purpose of this retrospective study was to explore the feasibility of a new surgical approach--endoscopic total parathyroidectomy with autotransplantation (ETP+AT)--and evaluate its practical application for patients with SHPT. METHODS: The study included 34 SHPT patients who underwent ETP+AT from among 67 cases at the Department of Minimally Invasive Surgery, the First Affiliated Hospital of Nanjing Medical University over a 3-year period. The other 33 patients underwent traditional total parathyroidectomy with autotransplantation (TP+AT). Two criteria were used as indications to perform ETP+AT in SHPT patients. The first was a high serum parathyroid hormone level (PTH >800 pg/ml) associated with hypercalcemia and/or hyperphosphatemia that which were refractory to medical treatment. The second criterion was the presence of clinical symptoms including pruritus, bone and joint pain, muscle weakness, progression of soft tissue calcification, and spontaneous fractures. Ultrasonography, (99m)Tc sestamibi scans, and computed tomography were used to evaluate the thyroid and parathyroid glands. RESULTS: There was no surgery-related mortality among any of the patients with ETP+AT. One patient underwent conventional neck exploration because of bleeding and injury of a unilateral recurrent laryngeal nerve after the operation. Preoperative symptoms were alleviated, and the serum PTH and alkaline phosphatase levels, hyperphosphatemia, and hypercalcemia were improved or normalized in most patients. Recurrence was observed in one patient with a sixth parathyroid gland behind his thyroid, and the patient required a second operation. Hypoparathyroidism was not found after the operation. The clinical data were compared between ETP+AT and TP+AT. CONCLUSIONS: ETP+AT is a safe option for the treatment of SHPT with low morbidity and mortality, shorter hospital stay and low recurrence rate. It is important to avoid intraoperative bleeding, identify all parathyroid glands during the surgery, and choose adequate parathyroid tissues for autografting.

Relationship between the GH-IGFs axis and the proliferation of bile duct cancer cell line QBC939 in vitro.

BACKGROUND: In recent years, recombined human growth hormone (rhGH) has been increasingly used in patients to help them recover from operation. But GH, as a mitogen, can promote cell renewal and increase malignant transformation. In the current study, we assessed the proliferation of a bile duct cancer cell line (QBC939) in vitro with GH and explored the possible relationship with the axis of GH-IGFs (insulin-like growth factors). METHODS: QBC939 cells in the exponential growth stage were harvested and divided into an experimental group (GH group) and a control group (NS group). The GH group was divided into four sub-groups according to the dose of GH and culture time (50 microg/L for 2 hours, 50 microg/L for 24 hours, 100 microg/L for 2 hours, 100 microg/L for 24 hours). The NS group was divided into two sub-groups (NS for 2 hours and NS for 24 hours). After 2 or 24 hours, IGF-1 and IGF-2 were detected using the enzyme-linked immunosorbent assay. The QBC939 cells cultured for 24 hours with two GH concentrations were made into single cell suspensions and samples underwent subsequent cell cycle evaluation. Messenger RNA of IGF-1 and IGF-2 receptor (IGF-1RmRNA and IGF-2RmRNA) were tested with the method of in situ hybridization. RESULTS: There was no statistically significant difference between the GH and NS groups after 2 hours of culture (P>0.05). But after 24 hours of culture, GH stimulated cell growth in vitro and also elevated the percentage in S phase and the proliferation index (P<0.05). IGF-1RmRNA and IGF-2RmRNA were expressed in QBC939 in contrast to the blank group. The expression of IGF-1RmRNA increased with the dose of GH, but IGF-2RmRNA did not. CONCLUSION: GH can stimulate QBC939 cell growth and proliferation in vitro and the mechanism is most likely by the GH-IGF-1-IGF-1R axis.

[Laparoscopic gastric resection in 50 cases of gastric benign diseases].

OBJECTIVE: To explore the feasibility, effect, and clinic value of total laparoscopic gastric resection in patients with benign gastric disease. METHODS: The clinical materials of 50 cases underwent total laparoscopic gastric resection (LG group) and 104 cases open surgery (OG group) between January 2002 and June 2006 were compared. The operation time, intraoperative blood loss, mean time of stay in hospital and postoperative complications were studied. RESULTS: All operations in LG group were successfully preformed with laparoscopic technique, and the mean operation time was 105 min, mean intraoperative blood loss was 50 ml, and mean hospital stay was 7 days. Incisional wound infection occurred in 2 cases and no serious complications occurred in this group. In OG group, the mean operation time was 118 min, mean intraoperative blood loss was 108 ml, and mean hospital stay was 12 days. Wound infection occurred in 7 cases, disorder of gastric emptying was found in 3 cases, fistula of anastomotic stoma happened in 1 case and bowel obstruction occurred in 1 case. There was significant difference in operation blood loss and hospital stay between the two groups (P < 0.05). CONCLUSIONS: Laparoscopic gastric resection is a safe and feasible minimally-invasive surgery, it brings less pain, less bleeding, shorter hospital stay.

Expression of COX-2 proteins in gastric mucosal lesions.

AIM: To investigate the expression of COX-2 proteins in gastric mucosal lesions and to assess the relationship between COX-2 expression and type, pathologic stage, differentiation, or lymph node metastasis in gastric cancer and the relationship between COX-2 expression and H pylori infection in gastric mucosal lesions. METHODS: Thirty patients with gastric carcinoma underwent surgical resection. Samples were taken from tumor site and paracancerous tissues, and ABC immunohistochemical staining was used to detect the expression of COX-2 proteins. H pylori was determined by rapid urea test combined with pathological stating/14C urea breath test. RESULTS: The positive rate and staining intensity of mutant COX-2 gene expression in gastric cancer were significantly higher than those in paracancerous tissues (66.7% vs 26.7%) (P<0.01, P<0.001). There was a significant correlation between COX-2 and pathologic stage or lymph node metastasis type of gastric carcinoma (76.0% vs 20.0%, 79.2% vs 16.7%) (P<0.05). No correlation was found between COX-2 expression and type or grade of differentiation (P>0.05). COX-2 expression of intestinal metaplasia (IM) or dysplasia (DYS) with positive H pylori was significantly higher than that with negative H pylori (50.6% vs 18.1%, 60.0% vs 33.3%) (P<0.05). CONCLUSION: COX-2 overexpression was found in a large proportion of gastric cancer tissues compared with matched non-cancerous tissues and was significantly associated with advanced tumor stage and lymph node metastasis. Overexpression of COX-2 plays an important role in tumor progression of gastric cancer. COX-2 may also play a role in the early development/promotion of gastric carcinoma and is associated with H pylori infection.

Multiple genetic alterations and behavior of cellular biology in gastric cancer and other gastric mucosal lesions:H.pylori infection, histological types and staging.

AIM:To investigate the expression of multiple genes and the behavior of cellular biology in gastric cancer (GC) and other gastric mucosal lesions and their relations to Helicobacter pylori (H. pylori) infection, tumor staging and histological subtypes.METHODS:Three hundred and twenty seven specimens of gastric mucosa obtained via endoscopy or surgical resection, and ABC immunohistochemical staining were used to detect the expression of p53, p16, Bcl-2 and COX-2 proteins.H. pylori was determined by rapid urea test combined with patholo-gical staining or 14 Curea breath test. Cellular image analysis was performed in 66 patients with intestinal metaplasia (IM) and/or dysplasia (Dys). In 30 of them, both cancer and the paracancerous tissues were obtained at the time of surgery. Histolo-gical pattern, tumor staging, lymph node metastasis, grading of differentiation and other clinical data were studied in the medical records.RESULTS:p16 expression of IM or Dys was significantly lower in positive H. pylori chronic atrophic gastritis (CAG) than those with negative H. pylori (CAG: 54.8% vs 88.0%, IM:34.4% vs 69.6%, Dys: 23.8% vs 53.6%, all P < 0.05), Bcl-2 or COX-2 expression of IM or Dys in positive H. pylori cases was signi-ficantly higher than that without H. pylori (Bcl-2: 68.8% vs 23.9%, 90.5% vs 60.7%; COX-2: 50.0% vs 10.8%, 61.8% vs 17.8%; all P <0.05). The mean number of most parame-ters of cellular image analysis in positive H. pylori group was significantly higher than that in negative H. pylori group (Ellipser: 53 plus minus 14, 40 plus minus 12&mgr;m, Area(1): 748 plus minus 572, 302 plus minus 202&mgr;m(2), Area(2): 3050 plus minus 1661, 1681 plus minus 1990&mgr;m(2), all P< 0.05; Ellipseb: 79 plus minus 23, 58 plus minus 15&mgr;m, Ratio-1: 22% plus minus5%,13% plus minus4%,Ratio-2:79% plus minus17%,53% plus minus20%,all P<0.01). There was significant correl-ation between Bcl-2 and histologic pattern of gastric carcinoma, and between COX-2 and tumor staging or lymph node metasta sis (Bcl-2: 75.0% vs16.7%; COX-2: 76.0% vs 20.0%, 79.2% vs 16.7%; all P< 0.05).CONCLUSION:p16, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infec-tion. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.