Design, Synthesis, Antibacterial, and Antifungal Evaluation of Phenylthiazole Derivatives Containing a 1,3,4-Thiadiazole Thione Moiety.

To effectively control the infection of plant pathogens, we designed and synthesized a series of phenylthiazole derivatives containing a 1,3,4-thiadiazole thione moiety and screened for their antibacterial potencies against Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, as well as their antifungal potencies against Sclerotinia sclerotiorum, Rhizoctonia solani, Magnaporthe oryzae and Colletotrichum gloeosporioides. The chemical structures of the target compounds were characterized by 1H NMR, 13C NMR and HRMS. The bioassay results revealed that all the tested compounds exhibited moderate-to-excellent antibacterial and antifungal activities against six plant pathogens. Especially, compound 5k possessed the most remarkable antibacterial activity against R. solanacearum (EC50 = 2.23 µg/mL), which was significantly superior to that of compound E1 (EC50 = 69.87 µg/mL) and the commercial agent Thiodiazole copper (EC50 = 52.01 µg/mL). Meanwhile, compound 5b displayed the most excellent antifungal activity against S. sclerotiorum (EC50 = 0.51 µg/mL), which was equivalent to that of the commercial fungicide Carbendazim (EC50 = 0.57 µg/mL). The preliminary structure-activity relationship (SAR) results suggested that introducing an electron-withdrawing group at the meta-position and ortho-position of the benzene ring could endow the final structure with remarkable antibacterial and antifungal activity, respectively. The current results indicated that these compounds were capable of serving as promising lead compounds.

AKR1C1 connects autophagy and oxidative stress by interacting with SQSTM1 in a catalytic-independent manner.

Targeting autophagy might be a promising anticancer strategy; however, the dual roles of autophagy in cancer development and malignancy remain unclear. NSCLC (non-small cell lung cancer) cells harbour high levels of SQSTM1 (sequestosome 1), the autophagy receptor that is critical for the dual roles of autophagy. Therefore, mechanistic insights into SQSTM1 modulation may point towards better approaches to treat NSCLC. Herein, we used multiple autophagy flux models and autophagy readouts to show that aldo-keto reductase family 1 member C1 (AKR1C1), which is highly expressed in NSCLC, promotes autophagy by directly binding to SQSTM1 in a catalytic-independent manner. This interaction may be strengthened by reactive oxygen species (ROS), important autophagy inducers. Further mechanistic research demonstrated that AKR1C1 interacts with SQSTM1 to augment SQSTM1 oligomerization, contributing to the SQSTM1 affinity for binding cargo. Collectively, our data reveal a catalytic-independent role of AKR1C1 for interacting with SQSTM1 and promoting autophagy. All these findings not only reveal a novel functional role of AKR1C1 in the autophagy process but also indicate that modulation of the AKR1C1-SQSTM1 interaction may be a new strategy for targeting autophagy.

Reassessment of the Effect of Transcutaneous Auricular Vagus Nerve Stimulation Using a Novel Burst Paradigm on Cardiac Autonomic Function in Healthy Young Adults.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) may modulate cardiac autonomic function. However, the response rate of the traditional tonic paradigm is low, and the results remain inconsistent. A recent pilot study presented a novel burst paradigm to activate the cardiac parasympathetic system, which might offer a new approach to treat cardiac autonomic function. The present study reassessed the effect of burst taVNS on modulating heart rate variability and explored the difference between burst and traditional tonic paradigms. MATERIALS AND METHODS: Forty-two young adults were recruited for this study. Each participant underwent three types of taVNS with sham (30 sec of stimulation), tonic (25 Hz, 500 µsec), and burst (five pulses at 500 Hz every 200 msec) paradigms, respectively, with simultaneous electrocardiogram recording. One-way analysis of variance, multivariate analysis of variance, and linear regression were used for analysis. Multiple testing was performed using Bonferroni correction. RESULTS: Both burst and tonic paradigms induced a significant decrease in heart rate, which continued until poststimulation, and increased cardiac parasympathetic activity. Moreover, two parasympathetic system indicators showed significant increase only in burst taVNS. The response rates during burst (35.7%) and tonic (38.1%) stimulations were both higher than that during sham stimulation (11.9%). The response to taVNS showed parameter specificity with few nonresponders to the tonic paradigm responding to the burst paradigm. The overall response rate increased from 38.1% in tonic taVNS to 54.8% in taVNS using both burst and tonic paradigms. For both burst and tonic responders, baseline cardiac parasympathetic activity was found to be significantly negatively correlated with changes during stimulation. CONCLUSION: The burst parameter could be used as an alternative strategy for regulating cardiac parasympathetic function by taVNS, which has the potential to be used as a complementary paradigm to traditional tonic taVNS for promoting clinical treatment efficacy.

Asprosin in the Paraventricular Nucleus Induces Sympathetic Activation and Pressor Responses via cAMP-Dependent ROS Production.

Asprosin is a newly discovered adipokine that is involved in regulating metabolism. Sympathetic overactivity contributes to the pathogenesis of several cardiovascular diseases. The paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the regulation of sympathetic outflow and blood pressure. This study was designed to determine the roles and underlying mechanisms of asprosin in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male adult SD rats under anesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded, and PVN microinjections were performed bilaterally. Asprosin mRNA and protein expressions were high in the PVN. The high asprosin expression in the PVN was involved in both the parvocellular and magnocellular regions according to immunohistochemical analysis. Microinjection of asprosin into the PVN produced dose-related increases in RSNA, MAP, and HR, which were abolished by superoxide scavenger tempol, antioxidant N-acetylcysteine (NAC), and NADPH oxidase inhibitor apocynin. The asprosin promoted superoxide production and increased NADPH oxidase activity in the PVN. Furthermore, it increased the cAMP level, adenylyl cyclase (AC) activity, and protein kinase A (PKA) activity in the PVN. The roles of asprosin in increasing RSNA, MAP, and HR were prevented by pretreatment with AC inhibitor SQ22536 or PKA inhibitor H89 in the PVN. Microinjection of cAMP analog db-cAMP into the PVN played similar roles with asprosin in increasing the RSNA, MAP, and HR, but failed to further augment the effects of asprosin. Pretreatment with PVN microinjection of SQ22536 or H89 abolished the roles of asprosin in increasing superoxide production and NADPH oxidase activity in the PVN. These results indicated that asprosin in the PVN increased the sympathetic outflow, blood pressure, and heart rate via cAMP-PKA signaling-mediated NADPH oxidase activation and the subsequent superoxide production.

Emerging role of m6A methylation modification in ovarian cancer.

m6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC.

Radiochromic Hydrogen-Bonded Organic Frameworks for X-ray Detection.

Porous materials have been investigated as efficient photochromic platforms for detecting hazardous radiation, while the utilization of hydrogen bonded organic frameworks (HOFs) in this field has remained intact. Herein, two HOFs were synthesized through self-assembly of tetratopic viologen ligand and formic acid (PFC-25, PFC-26), as a new class of "all-organic" radiochromic smart material, opening a gate for HOFs in this field. PFC-26 is active upon both X-ray and UV irradiation, while PFC-25 is only active upon X-ray irradiation. The same building block yet different radiochromic behaviors of PFC-25 and PFC-26 allow us to gain a deep mechanistic understanding of the factors that control the detection specificity. Theoretical and experimental studies reveal that the degree of π-conjugation of viologen ligand is highly related to the threshold energy of triggering a charge transfer, therefore being a vital factor for the particularity of radiochromic materials. Thanks to its convenient processibility, nanoparticle size, and UV silence, PFC-25 can be further fabricated into a portable naked-eye sensor for X-ray detection, which shows obvious color change with the merits of high transmittance contrast, good sensitivity (reproducible dose threshold of 3.5 Gy), and excellent stability. The work exhibits the promising practical potentials of HOF materials in photochromic technology.

[Effect of SIRT1 on delay of D-gal-induced premature ovarian failure in mice with ginsenoside Rg_1].

To explore the effect of slient mating type information regulation 2 homolog 1(SIRT1) on the delay of D-galactose(D-gal) induced premature ovarian failure in mice with ginsenoside Rg_1(Rg_1). Fifty-four female SPF BALB/c mice were randomly divided into PBS group, D-gal group, and Rg_1 group. In the D-gal group, D-galactose(200 mg·kg~(-1)·d~(-1)) was injected subcutaneously into the neck and back for 42 days. In the PBS group, the equal amount of phosphate buffered saline(PBS) was injected into the neck and back for 42 days. In addition to the therapy of D-gal group, Rg_1 group was given Rg_1(20 mg·kg~(-1)·d~(-1)) through the intraperitoneal injection on the 15 th day for 28 days. At the same time, the D-gal group and the PBS group were also given an equal amount of PBS through hintraperitoneal injection on the 15 th day for 28 days. The changes in body weight and ovarian weight coefficient of mice were detected. Expressions of estradiol 2(E_2), luteinizing hormone(LH), superoxide dismutase(SOD), catalase(CAT) and follicle-stimulating hormone(FSH) in peripheral blood were detected. Morphological changes of ovaries were detected by HE staining. Changes in expression of aging regulator SIRT1 were detected by fluorescent quantitative PCR and Western blot. The results showed that compared with the PBS group, the body weight growth rate of the D-gal group was significantly slowed, the ovarian weight coefficient was decreased, the serum levels of E_2, LH, SOD, CAT were significantly reduced, and FSH was significantly increased. After the administration with Rg_1, the body weight growth rate, ovarian weight coefficient, serum levels of E_2, LH, SOD, and CAT in the mice were higher than those in the D-gal group, while FSH was lower than those in the D-gal group. HE staining showed that the follicular morphology and structure of the PBS group were normal; the number of follicles in the D-gal group was reduced, the corpus luteum was vacuolated, and the number of atretic follicles was increased. Compared with the D-gal group, the number of follicles in the Rg_1 group was increased, whereas the number of corpus luteum was decreased. Compared with the PBS group, SIRT1 expression was down-regulated in the D-gal group, while SIRT1 expression was up-regulated in the Rg_1 group compared with the D-gal group. The results suggested that Rg_1 could delay D-gal-induced premature ovarian failure in a mouse model of premature ovarian failure, and SIRT1 played an important role in this.

Long noncoding RNA MALAT-1 inhibits apoptosis and matrix metabolism disorder in interleukin-1ß-induced inflammation in articular chondrocytes via the JNK signaling pathway.

Proinflammatory cytokine such as interleukin (IL)-1ß causes inflammation of articular cartilage. In this current study, we explored the chondroprotective effects of long noncoding RNA (lncRNA) MALAT-1 on cell proliferation, apoptosis, and matrix metabolism in IL-1ß-induced inflammation in articular chondrocytes. Articular chondrocytes from knee joints of normal rats were isolated and cultured, followed by identification through observation of toluidine blue and COL II immunocytochemical stainings. The proliferation of chondrocytes at passage 2 was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The inflammatory chondrocytes induced by 10 ng/mL IL-1ß were observed and identified by toluidine blue and COL II immunocytochemical stainings. pcDNA 3.1 and pcDNA-MALAT-1 were transfected in the chondrocytes. Ultrastructure of chondrocytes was observed by using a transmission electron microscope. The MTT assay was carried out to evaluate chondrocyte viability. Hoechst 33258 staining and flow cytometry were adopted to assess chondrocyte apoptosis. The chondrocytes at passage 2 with the biological characteristics of chondrocytes were used for subsequent experiments. In IL-1ß-treated chondrocytes, the growth rate of chondrocytes slowed down, the cells became narrow and long, the vacuoles were seen in the cells, and the morphology of the chondrocytes was irregular. The toluidine blue staining and the immunohistochemical staining of COL II became weaker. In response to IL-1ß induction, articular chondrocytes showed reduced MALAT-1 expression; moreover, obvious cartilage injury was observed with decreased chondrocyte viability and Col II expression and elevated chondrocyte apoptosis, MMP-13 expression, and p-JNK expression. With the treatment of pcDNA-MALAT-1, the cartilage injury was alleviated with increased chondrocyte viability and type II collagen (Col II) expression and reduced chondrocyte apoptosis, MMP-13 expression and p-JNK expression. Taken together these results, lncRNA MALAT-1 blocked the activation of the JNK signaling pathway; thereby, IL-1ß-induced inflammation in articular chondrocytes was reduced with enhanced chondrocyte proliferation and suppressed chondrocyte apoptosis and extracellular matrix degradation.

Pharmacokinetics, tissue distribution, plasma protein binding, and metabolism study of mefunidone, a novel pirfenidone derivative.

Mefunidone (MFD), a novel derivation of pirfenidone (PFD), exhibits promising anti-renal fibrosis activity. To avoid early development failures and attrition in clinical phase 1, an evaluation of the preclinical pharmacokinetic (PK) properties of MFD was conducted in this study. The absolute bioavailability was evaluated in Sprague Dawley rats and cynomolgus monkeys, who received an intragastric or intravenous administration at the dose of 31.25 mg/kg and 10 mg/kg, respectively. Tissue distribution and plasma protein binding studies were performed to evaluate the distribution characteristics of MFD. The enzymes involved in the metabolism of MFD were assayed by calculating the inhibition rate using the in vitro incubation system of human liver microsomes. The metabolic pathway of MFD was also examined in the in vitro incubation system as well as in rats in vivo. The results revealed satisfactory absorption of MFD in vivo, with an absolute bioavailability of MFD in rats and monkeys of approximately 77.2% and 70.0%, respectively. MFD was rapidly distributed to all tissues and was highly concentrated in the kidney, which was the target organ of MFD. The plasma protein binding rates in rat, monkey, and human plasma were 36.40%-41.68%, 30.88%-63.92%, and 37.75%-57.77%, respectively. MFD was primarily metabolized by the enzymes CYP3A4, CYP2C9, and CYP2C8. The metabolic pathway of MFD is nitrogen demethylation of the pyridine ring of the MFD nucleus, hydroxylation of the aromatic ring, and demethylation of the piperazine ring. In conclusion, MFD exhibited good PK properties in the initial preclinical PK study. The results strongly support further research to investigate the potential of MFD as a clinical anti-renal fibrosis drug.

[Pelvic MRI combined with TRUS-guided transperineal template mapping biopsy for the diagnosis of prostate cancer].

OBJECTIVE: To assess the clinical value and safety of pelvic MRI combined with transurethral ultrasound (TRUS)-guided transperineal template mapping biopsy (TTMB) in the diagnosis of prostate cancer. METHODS: A total of 164 men underwent MRI plus TRUS-guided TTMB for the diagnosis of prostate cancer from December 2015 to May 2018. The patients averaged 71.2 years of age and, based on the PSA level, were divided into four groups: PSA <10 µg/L (n = 28), PSA 10－20 µg/L (n = 56), PSA 20.01－100 µg/L (n = 53) and PSA >100 µg/L (n = 27). All the patients received digital rectal examination, pelvic MRI and TRUS-guided X+12-core TTMB. RESULTS: The procedures of TRUS-guided TTMB were successfully completed in all the patients, with an average number of 14.2 (14－16) cores and mean operation time of 18 (15－28) minutes. Post-biopsy complications included transient hematuria in 4 cases, perineal hematoma in 12 and fever in 1, but no acute urinary retention. Pathological results revealed 95 cases of prostate cancer, 2 cases of ductal epithelial carcinoma, 63 cases of prostatic hyperplasia with benign interstitial inflammation, and 4 cases of atypical prostatic hyperplasia. The positive biopsy rates in the PSA <10 µg/L, 10－20 µg/L, 20.01－100 µg/L and >100 µg/L groups were 25.00%, 42.86%, 73.58% and 100.00% respectively, with statistically significant difference between the PSA <10 µg/L group and the PSA 20.01－100 µg/L and >100 µg/L groups (P < 0.01), but not between the PSA <10 µg/L and PSA 10－20 µg/L groups (P = 0.086). CONCLUSIONS: Pelvic MRI combined with TRUS-guided X+12-core TTMB, with the advantages of high accuracy and low rate of complications, is an ideal approach to the diagnosis of prostate cancer.

Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury.

BACKGROUND: Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases. AIM: To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI). METHODS: Rats underwent BCNI or a sham operation and were treated with vehicle or ß-aminopropionitrile, a specific LOX activity inhibitor. 30 days after BCNI, rats were tested for erectile function before penile tissue harvest. LOX and extracellular matrix component expression levels in the corpus cavernosum, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), fibronectin (FN), collagen (COL) I, and COL IV, were evaluated by real-time quantitative polymerase chain reaction and western blot. Corporal fibrosis was evaluated by Masson trichrome staining. Localization of LOX and SMC content in the corpus cavernosum were assessed by immunohistochemistry. OUTCOMES: Ratio of intracavernous pressure to mean arterial blood pressure; LOX, MMPs, TIMPs, COL I, COL IV, and FN expression; penile fibrosis; penile SMC content. RESULTS: After BCNI, there was an increase in penile LOX expression and activity, increased penile fibrosis, decreased SMC content, and impaired erectile function. TIMP1, TIMP2, COL I, COL IV, and FN expression was markedly upregulated, whereas the enzyme activity of MMPs was decreased after BCNI. ß-Aminopropionitrile treatment, at least in part, prevented a decrease in the ratio of intracavernous pressure to mean arterial blood pressure, decreased penile expression of TIMP1, TIMP2, COL I, COL IV, and FN, increased MMP activity, prevented corporal fibrosis, and preserved SMC content. CLINICAL TRANSLATION: LOX over-activation contributes to penile fibrosis and LOX inhibition could be a promising strategy in preventing the progression of CNI-induced erectile dysfunction. STRENGTHS AND LIMITATIONS: This is the 1st study to demonstrate the role of LOX activation in penile fibrosis. However, the exact mechanism of how LOX influences extracellular matrix protein synthesis and SMC content preservation awaits further investigation. CONCLUSION: CNI induced LOX over-activation in cavernous tissue, and inhibition of LOX preserved penile morphology and improved erectile function in a rat model of BCNI. Wan Z-H, Li G-H, Guo Y-L, et al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313.

Association between UDP-glucuronosyltransferase 2B7 tagSNPs and breast cancer risk in Chinese females.

This retrospective study was performed to evaluate the association between the UGT2B7 tagSNPs (rs12233719, rs4356975, rs7435335 and rs7441774) and breast cancer in Chinese females. Blood samples were collected from 672 patients with breast cancer and 670 healthy controls for DNA extraction. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to analyze UGT2B7 polymorphisms. Dual-luciferase reporter assays were further performed to investigate the regulatory function of UGT2B7 tagSNPs. The frequency of rs7441774 G allele in the breast cancer cases was statistically significantly higher than in the controls (0.412 vs 0.358, P = .006; odds ratio [OR] = 1.27, 95% CI = 1.08-1.48). After adjusting for conventional risk factors, individuals with the GG genotype had a higher breast cancer risk than those with the AA genotype (adjusted OR = 1.63, 95% CI = 1.18-2.26; P = .008). The GCGG haplotype of UGT2B7 was also associated with breast cancer (OR = 1.22, 95% CI = 1.04-1.45; P = .027). Meanwhile, the rs7441774 G allele could significantly decrease the transcriptional activity of the UGT2B7 gene. This study indicates that UGT2B7 polymorphisms may play a crucial role in the occurrence and development of breast cancer in the Han Chinese population.

Field Performance of Open-Ended Prestressed High-Strength Concrete Pipe Piles Jacked into Clay.

The behavior of open-ended pipe piles is different from that of closed-ended pipe piles due to the soil plugging effect. In this study, a series of field tests were conducted to investigate the behavior of open-ended prestressed high-strength concrete (PHC) pipe piles installed into clay. Two open-ended PHC pipe piles were instrumented with Fiber Bragg Grating (FBG) sensors and jacked into clay for subsequent static loading tests. Soil plug length of the test piles was continuously measured during installation, allowing for calculation of the incremental filling ratio. The recorded data in static loading test were reported and analyzed. The distribution of residual forces after installation and the effect on the bearing capacity were also discussed in detail. The test piles were observed to be in partially plugged condition during installation. The measured ultimate shaft resistance and total resistance of the test piles were 639 and 1180 kN, respectively. The residual forces locked in the test piles after installation significantly affected the evaluation of the axial forces, and thus the shaft and end resistances. It tended to underestimate the end resistances and overestimate the shaft resistances if the residual forces were not considered in the loading test. However, the residual forces did not affect the total bearing capacity of open-ended PHC pipe piles in this study.

Identification and control of a poliomyelitis outbreak in Xinjiang, China.

BACKGROUND: The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. METHODS: We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. RESULTS: Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. CONCLUSIONS: The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.

Using a double-channel gastroscope reduces procedural time in performing gastric endoscopic submucosal dissection.

OBJECTIVE: Complications are important determining factors for safety of endoscopic submucosal dissection (ESD). ESD of large lesions is associated with increased procedural time. This study investigated whether double-channel gastroscope could be used to reduce procedural time in gastric antrum ESD. METHODS: A retrospective cohort study of 46 patients with one gastric antrum lesion resected by ESD was conducted between January 2013 and December 2015. The diameter of a lesion was from 2cm to 4cm in 46 patients. EUS before ESD was used to evaluate the submucosal vascular structure and the location of lesion in gastric wall. Forty six lesions had ESD with either the ordinary gastroscope (OS group) (n=24) or the double-channel gastroscope (DC group) (n=22). RESULTS: The mean procedural time was significantly lower in the DC group than in the OS group (49.1 minutes vs. 20.5 minutes, p=0.04). There were no significant differences in submucosal injection frequency, specimen size, en bloc resection rate and perforation rate between the two endoscopic groups. There was no recurrence in any case during the follow-up period. CONCLUSIONS: Our data suggest that ESD utilizing double-channel gastroscope may provide a better platform for quicker ESD with equal safety.

Potential signaling pathway of hypoxia-inducible factor in lung cancer and its gene polymorphism with lung cancer risk.

Lung cancer is becoming the leading cause of cancer death worldwide with highest morbidity and mortality, and knowing the pathogenesis and signaling pathway is very important and advances in the diagnosis and treatment of the disease are urgently needed. Gene polymorphism was reported to be associated with the lung cancer risk. We reviewed the potential signaling pathway of hypoxia-inducible factor in lung cancer and conducted a meta-analysis to explore its gene polymorphism with lung cancer risk. In the meta-analysis, hypoxia-inducible factor-1α (HIF-1α) G1790A A allele, AA genotype and GG genotype were associated with lung cancer risk (A allele: OR = 2.31, 95% CI: 1.77-3.02, p < 0.00001; AA genotype: OR = 4.52, 95% CI: 2.31-8.83, p < 0.0001; GG genotype: OR = 0.45, 95% CI: 0.33-0.63, p < 0.00001). Furthermore, HIF-1α C1772 TT genotype and CC genotype were associated with lung cancer risk, but the T allele was not. In conclusion, HIF-1α G1790A A allele, AA genotype and GG genotype, HIF-1α C1772 TT genotype and CC genotype were associated with lung cancer risk. However, more studies should be performed to confirm it.

Role of toll-like receptors in myocardial infarction.

Toll-like receptors (TLRs) play a pivotal role in both innate and adaptive immunity, and TLRs recognize invading pathogens through molecular pattern recognition, and ultimately lead to the activation of transcription factors and inflammatory responses. Myocardial infarction leads to changes in the remodeling of the left ventricle of the heart, and the degree and type of remodeling provides important diagnostic information for the therapeutic management of ischemic heart disease. Innate immune takes a most important role in myocardial infarction. There are some studies reporting that TLRs play an important role in the myocardial infarction. The literatures were searched extensively and this review was performed to review the role of TLRs in myocardial infarction.

Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis.

The generic mitogen-activated protein kinases (MAPK) signaling pathway is shared by four distinct cascades, including the extracellular signal-related kinases (ERK1/2), Jun amino-terminal kinases (JNK1/2/3), p38-MAPK and ERK5. Mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) pathway is reported to be associated with the cell proliferation, differentiation, migration, senescence and apoptosis. The literatures were searched extensively and this review was performed to review the role of MAPK/ERK signaling pathway in cell proliferation, differentiation, migration, senescence and apoptosis.

Cross-border collaboration between China and Myanmar for emergency response to imported vaccine derived poliovirus case.

BACKGROUND: This report describes emergency response following an imported vaccine derived poliovirus (VDPV) case from Myanmar to Yunnan Province, China and the cross-border collaboration between China and Myanmar. Immediately after confirmation of the VDPV case, China disseminated related information to Myanmar with the assistance of the World Health Organization. METHODS: A series of epidemiological investigations were conducted, both in China and Myanmar, including retrospective searches of acute flaccid paralysis (AFP) cases, oral poliovirus vaccine (OPV) coverage assessment, and investigation of contacts and healthy children. RESULTS: All children <2 years of age had not been vaccinated in the village where the VDPV case had lived in the past 2 years. Moreover, most areas were not covered for routine immunization in this township due to vaccine shortages and lack of operational funds for the past 2 years. CONCLUSIONS: Cross-border collaboration may have prevented a potential outbreak of VDPV in Myanmar. It is necessary to reinforce cross-border collaboration with neighboring countries in order to maximize the leverage of limited resources.

An outbreak following importation of wild poliovirus in Xinjiang Uyghur Autonomous Region, China, 2011.

BACKGROUND: After more than 10 years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region. METHODS: Acute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients. RESULTS: There were 21 WPV cases and 23 clinical compatible polio cases reported. WPV was isolated from 14 contacts of AFP cases and 13 in the healthy population. Incidence of WPV and clinical compatible polio cases were both highest among children <1 years, however, 24/44 (54.5%) polio cases were reported among adults aged 15-39 years. CONCLUSIONS: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Expansion of AFP case surveillance and use of serologic surveys to estimate population immunity should be conducted rapidly to guide preparedness and response planning for future WPV outbreaks.