[Mitochondrial DNA hydroxymethylation level in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To study the methylation level and dynamic change of 5-hydroxymethylcytosine (5hmC) in mitochondrial DNA (mtDNA) in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage. METHODS: A total of 24 male Sprague-Dawley rats aged 7 days were randomly divided into control group, 24-hour model group and 48-hour model group (n=8 each). Common carotid artery ligation combined with hypoxic treatment was performed to establish an animal model of hypoxic-ischemic brain damage. The rats in the control group were not given ligation or hypoxic treatment. Oxidative bisulfite sequencing was used to measure the level of 5hmC in the cerebral cortex. Western blot was used to measure the expression of 5hmC-related enzymes TET1, TET2 and DNMT1. RESULTS: The 24- and 48-hour model groups had a significantly higher level of 5hmC than the control group (P<0.05). Western blot showed a significant increase in the expression of DNMT1 in the 24- and 48-hour model groups (P<0.05). Compared with the control group, the 24- and 48-hour model groups had significant differences in the 5hmC level at multiple mitochondrial genetic loci (P<0.05). CONCLUSIONS: The level of DNMT1, a key enzyme for 5hmC modification in mtDNA, in the cerebral cortex increases in neonatal rats with hypoxic-ischemic brain damage, suggesting that there is an abnormal methylation level of 5hmC after hypoxic-ischemic brain damage, which might be associated with the regulation of hypoxic-ischemic brain damage.

Molecular regulatory mechanism of ferroptosis and its role in gastrointestinal oncology: Progress and updates.

Gastrointestinal (GI) tumors, including liver, pancreatic, gastric, and colorectal cancers, have a high incidence rate and low survival rate due to the lack of effective therapeutic methods and frequent relapses. Surgery and postoperative chemoradiotherapy have largely reduced the fatality rates for most GI tumors, but these therapeutic approaches result in poor prognoses due to severe adverse reactions and the development of drug resistance. Recent studies have shown that ferroptosis plays an important role in the onset and progression of GI tumors. Ferroptosis is a new non-apoptotic form of cell death, which is iron-dependent, non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species (ROS). The activation of ferroptosis can lead to tumor cell death. Thus, regulating ferroptosis in tumor cells may become a new therapeutic approach for tumors, making it become a research hotspot. Current studies suggest that ferroptosis is mainly triggered by the accumulation of lipid ROS. Furthermore, several studies have indicated that ferroptosis may be a new approach for the treatment of GI tumors. Here, we review current research progress on the mechanism of ferroptosis, current inducers and inhibitors of ferroptosis, and the role of ferroptosis in GI tumors to propose new methods for the treatment of such tumors.

[Effect of boron on the excitation temperature of inductively coupled plasma atomic emission spectroscopy].

The influence of boron existing in sample solution on the excitation temperature of the ICP was studied in the present paper. Method of Boltzmann plot of Fe lines were used for the excitation temperature determination. Slop of the plot was obtained from linearity regression. Experimental results showed that excitation temperature was varied with the reference values of Ig(gf), and boron concentration has no effect on the temperature. The conclusion is quite different from Ref[5] which was earlier reported by Broekaert.

[Determination of Cr, Ni, Cu, Mn, P, Si, Mo and Ti in high chromium cast iron by inductively coupled plasma atomic emission spectrometry].

The high-chromium cast iron sample was microwave-assisted digested with aqueous regia in a closed vessel. Series standards were prepared with matching Fe matrix and adding Y as internal standard. Line intensities of the prepared standards and the digested sample solutions were determined by inductively coupled plasma atomic emission spectrometry. Accuracy of the proposed method was verified by the analysis of three national standard Materials GSBH 41018, GBW 01120 and GBW 01121, and the results were well agreed with the certification data.

[Professor SHAO Ming-xi's experience in differentiation and treatment of arthralgia in breast cancer with acupuncture, moxibustion and tuina].

Professor SHAO Ming-xi 's experience in treatment of arthralgia in breast cancer is summarized. Professor SHAO believes that the dysfunction of liver, spleen and kidney is the primary and the invasion of the exogenous wind, cold and damp is the secondary in arthralgia in breast cancer. Emphasized on syndrome/pattern differentiation, this disorder is identified as 4 patterns, i.e. liver qi stagnation, blockage by phlegm and stasis, qi and blood deficiency and obstruction by wind, cold and damp. Acupuncture-moxibustion is applied to Hegu (LI 4), Taichong (LR 3) and Waiguan (TE 5). The supplementary acupoints are selected on the base of syndrome/pattern differentiation. Tuina is combined with acupuncture-moxibustion and the reinforcing and reducing techniques are used appropriately. Shaoyang meridian is specially considered, due to which, Waiguan (TE 5) and Zhongzhu (TE 3) of triple energizer meridian of hand-shaoyang and Yanglingquan (GB 34) and Zulinqi (GB 41) of gallbladder meridian of foot-shaoyang are combined. Additionally, it stresses the combination of the local and distal acupoints and the coordination of various therapies of TCM to achieve the better effect.

Retrievable puncture anchor traction method for endoscopic ultrasound-guided gastroenterostomy: A porcine study.

BACKGROUND: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is an alternative method for the surgical treatment of gastric outlet obstruction, but it is regarded as a challenging technique for endoscopists as the bowel is highly mobile and can tent away. Thus, the technique requires superb skill. In order to improve EUS-GE, we have developed a retrievable puncture anchor traction (RPAT) device for EUS-GE to address the issue of bowel tenting. AIM: To evaluate the feasibility of RPAT-assisted EUS-GE using an animal model. METHODS: Six Bama mini pigs each weighing between 15 and 20 kg underwent the RPAT-assisted EUS-GE procedure. Care was taken to ensure that the animals experienced minimal pain and discomfort. Two days prior to the procedure the animals were limited to a liquid diet. No oral intake was allowed on the day before the procedure. A fully covered metal stent was placed between the stomach and the intestine using the RPAT-assisted EUS-GE method. Infection in the animals was determined. Four weeks after the procedure, a standard gastroscope was inserted into the pig's intestine through a previously created fistula in order to check the status of the stents under anesthesia. The pig was euthanized after examination. RESULTS: The RPAT-assisted EUS-GE method allowed placement of the stents with no complications in all six animals. All the pigs tolerated a regular diet within hours of the procedure. The animals were monitored for four weeks after the RPAT-assisted EUS-GE, during which time all of the animals exhibited normal eating behavior and no signs of infection were observed. Endoscopic imaging performed four weeks after the RPAT-assisted EUS-GE showed that the stents remained patent and stable in all the animals. No tissue overgrowth or ingrowth was observed in any case. Each animal had a mature fistula, and the stents were removed without significant bleeding. Autopsies of all six pigs revealed complete adhesion between the intestine and the stomach wall. CONCLUSION: The RPAT method helps reduce mobility of the bowel. Therefore, the RPAT-assisted EUS-GE method is a minimally invasive treatment modality.

Delayed perforation after endoscopic resection of a colonic laterally spreading tumor: A case report and literature review.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been widely used for the treatment of early gastrointestinal cancer. Endoscopic piecemeal mucosal resection (EPMR) is derived from the combination of EMR and ESD. Delayed perforation with peritonitis after colonic EPMR is a rare but severe complication, sometimes requiring surgery. There are some associated risk factors, including patient- (location, diameter, and presence of fibrosis) and procedure-related factors. Early recognition and timely treatment are crucial for its management. CASE SUMMARY: We report a case in which delayed perforation with peritonitis was treated using endoscopic closure. A 54-year-old man was diagnosed with a 30-mm-diameter laterally spreading tumor in the colonic hepatic curvature. Fifteen hours after endoscopic resection, peritonitis caused by delayed perforation occurred and gradually aggravated. Conservative treatment was ineffective and no obvious perforation was observed. After timely endoscopic closure, the patient was discharged on postoperative day 4. CONCLUSION: In occasion of localized peritonitis aggravating without macroscopic perforation, endoscopic closure is an effective treatment for delayed perforation with stable vital signs in the early stage.

Endoscopic resection of the pancreatic tail and subsequent wound healing mechanisms in a porcine model.

BACKGROUND: Laparoscopic resection of the pancreatic body and tail is the predominant methodology to remove lesions in these locations; its safety and surgical planning are relatively mature, but it remains a complex and high-precision surgical operation, requiring abundant experience and skills in laparoscopic surgery, with a 10% rate of complications. AIM: To verify the feasibility and safety, as well as to examine the complications of endoscopic pancreatectomy and healing mechanisms of pancreatic wounds after endoscopic resection. METHODS: Transgastric endoscopic resections of varying sizes of pancreases were performed in 15 healthy Bama miniature pigs. The technical success rate, the incidence of serious complications, and the survival of the animals were studied. The healing of the wounds was evaluated by sacrificing the animals at various time points. Finally, the expression of transforming growth factor-ß1 and Smad3/Smad7 in the surgical site was examined by immunohistochemistry to explore the role of these factors in wound healing of the pancreas. RESULTS: Partial and total resections were successfully performed in two groups of animals, respectively. The technical success rate and the survival rate of the pigs were both 100%. We obtained 12 pancreatic tissue samples by endoscopic resection. The pancreatic wounds were closed with metal clips in one group and the wounds healed well by forming scars. There was a small amount of pancreatic leakage in the other group, but it can be fully encapsulated. The level of transforming growth factor-ß1 (TGF-ß1) in the wounds increased during the inflammatory and fibrous hyperplasia phases, and decreased in the scar phase. The expression of Smad3 paralleled that of TGF-ß1, while the expression of Smad7 had an inverse relationship with the expression of TGF-ß1. CONCLUSION: Purely transgastric endoscopic resection of the pancreas is a safe, effective, and feasible procedure, but the incidence of pancreatic leakage in total pancreatic tail resection is high. The expression of TGF-ß1 and Smad3/Samd7 is related to the progression of pancreatic wound healing.

Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening.

Currently, many strains of influenza A virus have developed resistance against anti-influenza drugs, and it is essential to find new chemicals to combat this virus. The influenza polymerase with three proteins, PA, PB1 and PB2, is a crucial component of the viral ribonucleoprotein (RNP) complex. Here, we report the identification of a hit compound 221 by surface plasmon resonance (SPR) direct binding screening on the C-terminal of PA (PAC). Compound 221 can subdue influenza RNP activities and attenuate influenza virus replication. Its analogs were subsequently investigated and twelve of them could attenuate RNP activities. One of the analogs, compound 312, impeded influenza A virus replication in Madin-Darby canine kidney cells with IC50 of 27.0 ± 16.8 µM. In vitro interaction assays showed that compound 312 bound directly to PAC with Kd of about 40 µM. Overall, the identification of novel PAC-targeting compounds provides new ground for drug design against influenza virus in the future.

Toxic effects of zearalenone and its derivatives alpha-zearalenol on male reproductive system in mice.

The current study evaluated effects of zearalenone (ZEA) and its derivative alpha-zearalenol (alpha-ZOL) on male mouse semen quality, fertility and serum testosterone concentrations. Adult male mice were exposed to intraperitoneal (i.p.) injection of ZEA or alpha-ZOL at 0, 25, 50, and 75 mg/kg body weight (b.w.) daily for 7 days, and then mated with sexually mature untreated female mice. Semen quality, serum testosterone concentrations and fertility of treated mice were assessed. The results showed that the number of abnormal spermatozoa increased and the amount of live spermatozoa decreased significantly in males treated with ZEA at all doses. As well, a significant decrease in spermatozoa with integrated acrosome was observed in mice treated with 50 and 75 mg/kg b.w. alpha-ZOL. Significantly low pregnancy rate was observed when females were mated with ZEA or alpha-ZOL exposed males. Male mice exposed to ZEA had significant reductions in b.w. and relative epididymis weights. However, relative seminal vesicle weights were higher than those of controls. Conversely, significant increases in b.w. and relative preputial gland weight were observed in mice exposed to alpha-ZOL. Testicular and cauda epididymal sperm counts, efficiency of sperm production and serum testosterone concentrations were significantly reduced in mice treated with ZEA or alpha-ZOL at all doses in a dose-dependent manner. In conclusion, we demonstrate that ZEA or alpha-ZOL have adverse effects on reproductive system of adult male mice.

Circular RNA circ-LDLRAD3 as a biomarker in diagnosis of pancreatic cancer.

AIM: To analyze the diagnostic value of a circular RNA (circRNA), circ-LDLRAD3, in pancreatic cancer. METHODS: Expression levels of circ-LDLRAD3 were tested in both cells and clinical samples; the latter included 30 paired pancreatic cancer tissues and adjacent non-tumorous tissues, 31 plasma samples from patients with pancreatic cancer, and 31 plasma samples from healthy volunteers. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to measure expression levels of circ-LDLRAD3 in cells and clinical samples; then, the relationship between clinicopathological factors of patient samples and expression of circ-LDLRAD3 in pancreatic cancer was analyzed. The diagnostic value of circ-LDLRAD3 was verified by receiver operating characteristic (ROC) curve analysis. RESULTS: Circ-LDLRAD3 was up-regulated in pancreatic cancer cell lines (P < 0.01), pancreatic cancer tissues (P < 0.01), and plasma samples from patients with pancreatic cancer (P < 0.01). High expression of circ-LDLRAD3 was significantly associated with venous invasion, lymphatic invasion, and metastasis. The area under the ROC curve of circ-LDLRAD3 alone or combination with CA19-9 was 0.67 and 0.87, respectively, with a sensitivity and specificity of 0.5738 (alone) and 0.7049 (alone), and 0.8033 (combination) and 0.9355 (combination), respectively. CONCLUSION: These data suggest that circ-LDLRAD3 may be a biomarker in the diagnosis of pancreatic cancer.

Curcumin enhances the effects of irinotecan on colorectal cancer cells through the generation of reactive oxygen species and activation of the endoplasmic reticulum stress pathway.

Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan's effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins. We found that cell viability was inhibited and apoptosis was increased, accompanied by ROS generation and ER stress activation in CRC cells treated with curcumin alone or in combination with irinotecan. Blocking ROS production attenuated the expression of two markers of ER stress: binding of immunoglobulin protein (BIP) and CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP expression using RNA interference also inhibited ROS generation. These results demonstrated that curcumin could enhance the effects of irinotecan on CRC cells by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and that these effects may be mediated, in part, by ROS generation and activation of the ER stress pathway.

Effects of premedication with Pronase for endoscopic ultrasound of the stomach: A randomized controlled trial.

AIM: To analyze the effects of premedication with Pronase for endoscopic ultrasound (EUS) examination of the stomach. METHODS: This was a prospective, randomized and controlled clinical study. All patients were randomly assigned to either the Pronase group or placebo group. The pretreatment solution was a mixed solution of 20000 U of Pronase and 60 mL sodium bicarbonate solution in the Pronase group, while an equal amount of sodium bicarbonate solution was administered to the placebo group. All operators, image evaluators and experimental recorders in EUS did not participate in the preparation and allocation of pretreatment solution. Two blinded investigators assessed the obscurity scores for the EUS images according to the size of artifacts (including ultrasound images of the gastric cavity and the gastric wall). Differences in imaging quality, the duration of examination and the usage of physiological saline during the examination process between the Pronase group and the control group were compared. RESULTS: No differences existed in patient demographics between the two groups. For the gastric cavity, the Pronase group had significantly lower mean obscurity scores than the placebo group (1.0476 ± 0.77 vs 1.6129 ± 0.96, respectively, P = 0.000). The mean obscurity scores for the gastric mucosal surface were significantly lower in the Pronase group than the placebo group (1.2063 ± 0.90 vs 1.7581 ± 0.84, respectively, P = 0.001). The average EUS procedure duration for the Pronase group was 11.60 ± 3.32 min, which was significantly shorter than that of the placebo group (13.13 ± 3.81 min, P = 0.007). Less saline was used in the Pronase group than the placebo group, and the difference was significant (417.94 ± 121.38 mL vs 467.42 ± 104.52 mL, respectively, P = 0.016). CONCLUSION: The group that had Pronase premedication prior to the EUS examination had clearer images than the placebo group. With Pronase premedication, the examination time was shorter, and the amount of saline used during the EUS examination was less.

Stent displacement in endoscopic pancreatic pseudocyst drainage and endoscopic management.

A pancreatic pseudocyst (PPC) is a collection of pancreatic fluid enclosed by a non-epithelialized, fibrous or granulomatous wall. Endoscopic pancreatic pseudocyst drainage (PPD) has been widely used clinically to treat PPCs. The success and complications of endoscopic PPD are comparable with surgical interventions. Stent displacement is a rare complication after endoscopic PPD. Almost all the complications of endoscopic PPD have been managed surgically, and there is rare report involving the endoscopic treatment of intraperitoneal stent displacement. We report here a case of stent displacement after endoscopic ultrasound- and fluoroscopy-guided PPD in a 41-year-old female patient with a PPC in the tail of the pancreas. The endoscopic treatment was successfully performed to remove the displaced stent. The clinical course of the patient was unremarkable. The cyst had significantly reduced and disappeared by 12 wk. We found that both endoscopic ultrasound and fluoroscopy should be used during endoscopic PPD to avoid stent displacement. The displaced stent can be successfully treated by endoscopic removal.

High-density genetic linkage map construction and QTL mapping of grain shape and size in the wheat population Yanda1817 × Beinong6.

High-density genetic linkage maps are necessary for precisely mapping quantitative trait loci (QTLs) controlling grain shape and size in wheat. By applying the Infinium iSelect 9K SNP assay, we have constructed a high-density genetic linkage map with 269 F 8 recombinant inbred lines (RILs) developed between a Chinese cornerstone wheat breeding parental line Yanda1817 and a high-yielding line Beinong6. The map contains 2431 SNPs and 128 SSR & EST-SSR markers in a total coverage of 3213.2 cM with an average interval of 1.26 cM per marker. Eighty-eight QTLs for thousand-grain weight (TGW), grain length (GL), grain width (GW) and grain thickness (GT) were detected in nine ecological environments (Beijing, Shijiazhuang and Kaifeng) during five years between 2010-2014 by inclusive composite interval mapping (ICIM) (LOD ≥ 2.5). Among which, 17 QTLs for TGW were mapped on chromosomes 1A, 1B, 2A, 2B, 3A, 3B, 3D, 4A, 4D, 5A, 5B and 6B with phenotypic variations ranging from 2.62% to 12.08%. Four stable QTLs for TGW could be detected in five and seven environments, respectively. Thirty-two QTLs for GL were mapped on chromosomes 1B, 1D, 2A, 2B, 2D, 3B, 3D, 4A, 4B, 4D, 5A, 5B, 6B, 7A and 7B, with phenotypic variations ranging from 2.62% to 44.39%. QGl.cau-2A.2 can be detected in all the environments with the largest phenotypic variations, indicating that it is a major and stable QTL. For GW, 12 QTLs were identified with phenotypic variations range from 3.69% to 12.30%. We found 27 QTLs for GT with phenotypic variations ranged from 2.55% to 36.42%. In particular, QTL QGt.cau-5A.1 with phenotypic variations of 6.82-23.59% was detected in all the nine environments. Moreover, pleiotropic effects were detected for several QTL loci responsible for grain shape and size that could serve as target regions for fine mapping and marker assisted selection in wheat breeding programs.

Tumor-suppressive microRNA-449a induces growth arrest and senescence by targeting E2F3 in human lung cancer cells.

MicroRNA-449a (miR-449a) was significantly downregulated in 156 lung cancer tissues (p<0.001). We found that the low expression of miR-449a was highly correlated with cancer recurrence and survival of lung cancer patients. The transient introduction of miR-449a caused cell cycle arrest and cell senescence in A549 and 95D cells. Further studies revealed that E2F3 was a direct target of miR-449a in lung cancer cells. miR-449a also suppressed tumor formation in vivo in nude mice. These results suggest that miR-449a plays an important role in lung cancer tumorigenesis and that miR-449a might predict cancer recurrence and survival of lung cancer patients.

[Bad tourist behaviors and their environmental impacts on Xixi National Wetland Park in Hangzhou].

By the methods of site investigation, data collection and correlation analysis, the bad tourist behaviors and their environmental impacts on Xixi National Wetland Park in 2006 were studied. The occurrence probabilities of three bad tourist behaviors, i.e., picking, trampling, and littering were 6.5%, 10.3% and 12.6%, respectively. Picking probability was primarily related to the vegetation types along walkways, while the scale of heavy trampling was negatively correlated with tour distance from the entrance. Waste production by each tourist was 782 g x d(-1) on average. The waste from littering amounted for 13.6% of the total. Tourist flow fluctuations of daily, weekly, and monthly perspectives for the study area showed high seasonality and successive days of overloaded tourist flows during peak seasons, which caused an increase of bad tourist behaviors. However, the water quality in the Park was not affected because of the improvement of dredging facilities.

One-pot synthesis of quinoline-based tetracycles by a tandem three-component reaction.

A practical one-pot synthetic strategy for the efficient synthesis of a range of structurally interesting and bioactive quinoline-based tetracycles has been developed. A key step in the synthesis is a tandem three-component reaction of heteroaromatic amine, methyl 2-formylbenzoate and (t)butyl isonitrile, followed by TFA-mediated lactamization via intramolecular aminolysis of an adjacent ester. Results related to a kinase-panel screening for several selected compounds are also discussed in this article.

Dendrimer interior functional group conversion and dendrimer metamorphosis--new approaches to the synthesis of oligo(dibenzyl sulfone) and oligo(phenylenevinylene) dendrimers.

A series of [G1] to [G3]-oligo(dibenzylsulfide) dendrimers containing up to 21 interior dibenzylsulfide moieties was prepared as starting materials toward the syntheses of two new series of oligo(dibenzyl sulfone) and oligo(phenylenevinylene) dendrimers using two different dendrimer-to-dendrimer conversion strategies. The first strategy entailed the interior functionalization of the [G1] to [G3]-oligo(dibenzylsulfide)s to the corresponding [G1] to [G3]-oligo(dibenzyl sulfone)s via hydrogen peroxide oxidation. Successful conversions of up to 21 interior dibenzylsulfide moieties to the corresponding dibenzyl sulfone groups were demonstrated. The second involved the skeletal rearrangements, also named as dendrimer metamorphosis, of the [G1] and [G2]-oligo(dibenzyl sulfone) dendritic backbones to the corresponding [G1] and [G2]-oligo(phenylenevinylene)s dendrimers via the Ramberg-Backlund (RB) reaction. Up to nine RB rearrangements on a dendrimer skeleton were realized and the conversion efficiency of each single RB rearrangement reaction was found to be 96%.