Application of the patient-reported outcome-based postoperative symptom management model in lung cancer: a multicenter randomized controlled trial protocol.

INTRODUCTION: Lung cancer is the most common cancer in China, with the highest mortality rate. Surgery is the primary treatment for early lung cancer. However, patients with lung cancer have a heavy burden of symptoms within 3 months after surgery, which seriously affects their quality of life (QOL). The symptom management model based on the patient-reported outcome (PRO) is considered the best caregiving model. The clinical evidence about the symptom management of lung cancer within 3 months after the operation is very limited. Herein, we propose a randomized controlled trial to evaluate the PRO score-based monitoring and alert system for follow-up on psychological and physiological symptoms of lung cancer patients within 3 months after surgery and further investigate the effect of intervention measures based on this PRO score-based system. METHODS AND ANALYSIS: This multicenter, open-label, randomized, parallel superiority trial will be conducted at four hospitals in China. A total of 440 lung cancer patients will be recruited in this study, who will be randomly assigned to the intervention group or the control group in a ratio of 1:1. Any of the target symptoms reaches the preset threshold (score ≥ 4), the patients will accept the symptom management advices based on the PRO. The patients in the control group will follow the current standard procedure of symptom management. The symptom management system is an electronic management system based on WeChat mini programs. All patients will be evaluated for symptoms through the lung cancer module of the MDASI lung cancer-specific scale on the day before surgery, days 1, 3, 5, and 7 after surgery, and once a week during the 12-week post-discharge period. Simultaneously, the EORTC QLQ-C30 scale will be used to evaluate patients' quality of life at baseline and the fourth and twelfth week after the surgery. The mean number of symptom threshold events of the intervention and the control groups were compared by t-test, and the changes of PRO were compared by a mixed effect model. The primary endpoint has been set as the 12-week post-discharge period. DISCUSSION: This study will test the feasibility of the symptom management system based on the mobile social media applet in postoperative caregiving and the efficacy of psychiatrist-assisted treatment and provide evidence in managing the symptoms of patients in the medium and long term. TRIALS REGISTRATION: Trials registration number: ChiCTR 2200058876, Registered 18 April 2022.

circNINL facilitates aerobic glycolysis, proliferation, invasion, and migration in lung cancer by sponging miR-3918 to mediate FGFR1 expression.

Previously characterized as an oncogenic player in breast cancer, the function of circular RNA NINL (circNINL) in lung cancer (LC) remained elusive. This study aimed to delineate the biological role of circNINL in LC and to unveil its potential molecular mechanisms. We discovered elevated expression levels of circNINL and Fibroblast Growth Factor Receptor 1 (FGFR1) concomitant with diminished expression of microRNA-3918 (miR-3918) in LC specimens. Knockdown of circNINL led to a marked decrease in cell proliferation, migration, invasion, and aerobic glycolysis, alongside an upsurge in apoptosis in LC cells. Either downregulation of miR-3918 or overexpression of FGFR1 mitigated the suppressive impact of circNINL knockdown on LC pathogenesis. Mechanistic studies validated that circNINL served as a competitive endogenous RNA for miR-3918, thus influencing FGFR1 expression. Further, in vivo experiments using nude mouse xenograft models underscored that silencing circNINL substantially curtailed tumor growth in LC. Collectively, these findings illuminate that circNINL exacerbates LC malignancy via the miR-3918/FGFR1 axis, a process integrally linked with the activation of aerobic glycolysis.

Microbial agents obtained from tomato straw composting effectively promote tomato straw compost maturation and improve compost quality.

Appropriate management of agricultural organic waste (AOW) presents a significant obstacle in the endeavor to attain sustainable agricultural development. The proper management of AOW is a necessity for sustainable agricultural development. This can be done skillfully by incorporating microbial agents in the composting procedure. In this study, we isolated relevant bacteria strains from tomato straw AOW, which demonstrated efficient degradation of lignocellulose without any antagonistic effects in them. These strains were then combined to create a composite microbial agent called Zyco Shield (ZS). The performance of ZS was compared with a commercially effective microorganism (EM) and a control CK. The results indicate that the ZS treatment significantly prolonged the elevated temperature phase of the tomato straw pile, showing considerable degradation of lignocellulosic material. This substantial degradation did not happen in the EM and CK treatments. Moreover, there was a temperature rise of 4-6 â„ƒ in 2 days of thermophilic phase, which was not the case in the EM and CK treatments. Furthermore, the inoculation of ZS substantially enhanced the degradation of organic waste derived from tomato straw. This method increased the nutrient content of the resulting compost and elevated the enzymatic activity of lignocellulose-degrading enzymes, while reducing the urease enzyme activity within the pile. The concentrations of NH4+-N and NO3--N showed increases of (2.13% and 47.51%), (14.81% and 32.17%) respectively, which is again very different from the results of the EM and CK treatments. To some extent, the alterations observed in the microbial community and the abundance of functional microorganisms provide indirect evidence supporting the fact that the addition of ZS microbial agent facilitates the composting process of tomato straw. Moreover, we confirmed the degradation process of tomato straw through X-ray diffraction, Fourier infrared spectroscopy, and by scanning electron microscopy to analyze the role of ZS microbial inoculum composting. Consequently, reinoculation compost strains improves agricultural waste composting efficiency and enhances product quality.

Drug-coated balloons for the treatment of ostial left anterior descending or ostial left circumflex artery lesions: a patient-level propensity score-matched analysis.

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS: The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Lipid mediator resolvin D2 inhibits ATP currents in rat primary sensory neurons.

Resolvin D2 (RvD2), an endogenous lipid mediator derived from docosahexaenoic acid, has been demonstrated to have analgesic effects. However, little is known about the mechanism underlying RvD2 in pain relief. Herein, we demonstrate that RvD2 targeted the P2X3 receptor as an analgesic. The electrophysiological activity of P2X3 receptors was suppressed by RvD2 in rat dorsal root ganglia (DRG) neurons. RvD2 pre-application dose-dependently decreased α,ß-methylene-ATP (α,ß-meATP)-induced inward currents. RvD2 remarkably decreased the maximum response to α,ß-meATP, without influencing the affinity of P2X3 receptors. RvD2 also voltage-independently suppressed ATP currents. An antagonist of the G protein receptor 18 (GPR18), O-1918, prevented the RvD2-induced suppression of ATP currents. Additionally, intracellular dialysis of the Gαi/o -protein antagonist pertussis toxin (PTX), the PKA antagonist H89, or the cAMP analog 8-Br-cAMP also blocked the RvD2-induced suppression. Furthermore, α,ß-meATP-triggered depolarization of membrane potential along with the action potential bursts in DRG neurons were inhibited by RvD2. Lastly, RvD2 attenuated spontaneous nociceptive behaviors as well as mechanical allodynia produced by α,ß-meATP in rats via the activation of the peripheral GPR18. These findings indicated that RvD2 inhibited P2X3 receptors in rat primary sensory neurons through GPR18, PTX-sensitive Gαi/o -proteins, and intracellular cAMP/PKA signaling, revealing a novel mechanism that underlies its analgesic effects by targeting P2X3 receptors.

CCK-8 enhances acid-sensing ion channel currents in rat primary sensory neurons.

Cholecystokinin (CCK) is a peptide that has been implicated in pain modulation. Acid sensitive ion channels (ASICs) also play an important role in pain associated with tissue acidification. However, it is still unclear whether there is an interaction between CCK signaling and ASICs during pain process. Herein, we report that a functional link between them in rat dorsal root ganglion (DRG) neurons. Pretreatment with CCK-8 concentration-dependently increased acid-evoked ASIC currents. CCK-8 increased the maximum response of ASICs to acid, but did not changed their acid sensitivity. Enhancement of ASIC currents by CCK-8 was mediated by the stimulation of CCK2 receptor (CCK2R), rather than CCK1R. The enhancement of ASIC currents by CCK-8 was prevented by application of either G-protein inhibitor GDP-ß-S or protein kinase C (PKC) inhibitor GF109203×, but not by protein kinase A (PKA) inhibitor H-89 or JNK inhibitor SP600125. Moreover, CCK-8 increased the number of action potentials triggered by acid stimuli by activating CCK2R. Finally, CCK-8 dose-dependently exacerbated acid-induced nociceptive behavior in rats through local CCK2R. Together, these results indicated that CCK-8/CCK2R activation enhanced ASIC-mediated electrophysiological activity in DRG neurons and nociception in rats. The enhancement effect depended on G-proteins and intracellular PKC signaling rather than PKA and JNK signaling pathway. These findings provided that CCK-8/CCK2R is an important therapeutic target for ASIC-mediated pain.

Incidence, risk factors, and clinical sequelae of incomplete stent apposition after sirolimus-eluting stent.

Incomplete stent apposition has been documented after sirolimus-eluting stent implantation. However, its clinical sequelae remain controversial. To identify the incidence and its clinical consequences of ISA, IVUS was performed on 78 patients. In spite of well apposition immediately after the deployment, late stent malapposition occurred after 6-months follow-up. A total of 7 patients who received SES showed ISA. There were no significant differences in IVUS measurements between patients with or without ISA. However, there was an increase in external elastic membrane area in ISA group than non-ISA group (19.69 ± 3.50 vs. 15.05 ± 2.56 mm2, P<0.05). There were positive clinical events for ISA cases at 6-months clinical follow-up. Univariate and multivariable analyses indicated that hs-CRP, miR-21, and MMP-2 were risk factor for ISA. ISA was observed in 9% of patients after SES implantation, which was related to vessel positive remodeling. The incidence of MACEs in patients with ISA was higher than those without ISA. However, careful long-term follow-up remains to be clarified.

Metformin inhibits spontaneous excitatory postsynaptic currents in spinal dorsal cord neurons from paclitaxel-treated rats.

Introduction: Cancer patients treated with paclitaxel often develop chemotherapy-induced peripheral neuropathy, which has not been effectively treated with drugs. The anti-diabetic drug metformin is effective in the treatment of neuropathic pain. The aim of this study was to elucidate effect of metformin on paclitaxel-induced neuropathic pain and spinal synaptic transmission. Methods: Electrophysiological experiments on rat spinal slices were performed in vitro and mechanical allodynia quantified in vitro. Results: The present data demonstrated that intraperitoneal injection of paclitaxel produced mechanical allodynia and potentiated spinal synaptic transmission. Intrathecal injection of metformin significantly reversed the established mechanical allodynia induced by paclitaxel in rats. Either spinal or systemic administration of metformin significantly inhibited the increased frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in spinal dorsal horn neurons from paclitaxel-treated rats. We found that 1 h incubation of metformin also reduced the frequency rather than the amplitude of sEPSCs in the spinal slices from paclitaxel-treated rats. Discussion: These results suggested that metformin was able to depress the potentiated spinal synaptic transmission, which may contribute to alleviating the paclitaxel-induced neuropathic pain.

Characterization of Extensively Drug-Resistant Salmonella enterica Serovar Kentucky Sequence Type 198 Isolates from Chicken Meat Products in Xuancheng, China.

The purpose of this study was to characterize extensively drug-resistant Salmonella enterica serovar Kentucky sequence type 198 (ST198) isolates from chicken meat products. Ten S. Kentucky strains obtained from chicken meat products in Xuancheng, China, carried 12 to 17 resistance genes, such as blaCTX-M-55, rmtB, tet(A), floR, and fosA3, combined with mutations within gyrA (S83F and D87N) and parC (S80I), resulting in resistance to numerous antimicrobial agents, including the clinically important antibiotics cephalosporin, ciprofloxacin, tigecycline, and fosfomycin. These S. Kentucky isolates shared a close phylogenetic relationship (21 to 36 single-nucleotide polymorphisms [SNPs]) and showed close genetic relatedness to two human clinical isolates from China. Three S. Kentucky strains were subjected to whole-genome sequencing using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) technology. All antimicrobial resistance genes were located on their chromosomes and clustered in one multiresistance region (MRR) and Salmonella genomic island (SGI) SGI1-K. The MRRs in three S. Kentucky strains were bounded by IS26 at both ends and were inserted downstream of the bcfABCDEFG cluster with 8-bp direct repeats. The MRRs were related to those of IncHI2 plasmids but differed by insertions, deletions, and rearrangements of multiple segments involving resistance genes and plasmid backbones. This finding suggests that the MRR fragment possibly originates from IncHI2 plasmids. Four SGI1-K variants with slight differences were identified in 10 S. Kentucky strains. Mobile elements, particularly IS26, play an essential role in forming distinct MRRs and SGI1-K structures. In conclusion, the emergence of extensively drug-resistant S. Kentucky ST198 strains containing numerous chromosomally located resistance genes is alarming and needs continued surveillance. IMPORTANCE Salmonella spp. are important foodborne pathogens, and multidrug-resistant (MDR) Salmonella strains have become a serious threat to clinical therapy. MDR S. Kentucky ST198 strains have been increasingly reported from various sources and have become a global risk. In this study, we described extensively drug-resistant S. Kentucky ST198 strains from chicken meat products from a city in China. Numerous resistance genes are clustered in the chromosomes of S. Kentucky ST198 strains, possibly acquired with the help of mobile elements. This would facilitate the spread of numerous resistance genes as intrinsic chromosomal genes within this global epidemic clone, with the potential to capture more resistance genes. The emergence and dissemination of extensively drug-resistant S. Kentucky ST198 pose a severe clinical and public health threat; therefore, continuous surveillance is warranted.

Group II metabotropic glutamate receptor activation attenuates acid-sensing ion channel currents in rat primary sensory neurons.

Acid-sensing ion channels (ASICs) play an important role in pain associated with tissue acidification. Peripheral inhibitory group II metabotropic glutamate receptors (mGluRs) have analgesic effects in a variety of pain conditions. Whether there is a link between ASICs and mGluRs in pain processes is still unclear. Herein, we show that the group II mGluR agonist LY354740 inhibited acid-evoked ASIC currents and action potentials in rat dorsal root ganglia neurons. LY354740 reduced the maximum current response to protons, but it did not change the sensitivity of ASICs to protons. LY354740 inhibited ASIC currents by activating group II mGluRs. We found that the inhibitory effect of LY354740 was blocked by intracellular application of the Gi/o protein inhibitor pertussis toxin and the cAMP analogue 8-Br-cAMP and mimicked by the protein kinase A (PKA) inhibitor H-89. LY354740 also inhibited ASIC3 currents in CHO cells coexpressing mGluR2 and ASIC3 but not in cells expressing ASIC3 alone. In addition, intraplantar injection of LY354740 dose-dependently alleviated acid-induced nociceptive behavior in rats through local group II mGluRs. Together, these results suggested that activation of peripheral group II mGluRs inhibited the functional activity of ASICs through a mechanism that depended on Gi/o proteins and the intracellular cAMP/PKA signaling pathway in rat dorsal root ganglia neurons. We propose that peripheral group II mGluRs are an important therapeutic target for ASIC-mediated pain.

Group II metabotropic glutamate receptor activation suppresses ATP currents in rat dorsal root ganglion neurons.

P2X3 receptors and group II metabotropic glutamate receptors (mGluRs) have been found to be expressed in primary sensory neurons. P2X3 receptors participate in a variety of pain processes, while the activation of mGluRs has an analgesic effect. However, it's still unclear whether there is a link between them in pain. Herein, we reported that the group II mGluR activation inhibited the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons. Group II mGluR agonist LY354740 concentration-dependently decreased P2X3 receptor-mediated and α,ß-methylene-ATP (α,ß-meATP)-evoked inward currents in DRG neurons. LY354740 significantly suppressed the maximum response of P2X3 receptor to α,ß-meATP, but did not change their affinity. Inhibition of ATP currents by LY354740 was blocked by the group II mGluR antagonist LY341495, also prevented by the intracellular dialysis of either the Gi/o protein inhibitor pertussis toxin, the cAMP analog 8-Br-cAMP, or the protein kinase A (PKA) inhibitor H-89. Moreover, LY354740 decreased α,ß-meATP-induced membrane potential depolarization and action potential bursts in DRG neurons. Finally, intraplantar injection of LY354740 also relieved α,ß-meATP-induced spontaneous nociceptive behaviors and mechanical allodynia in rats by activating peripheral group Ⅱ mGluRs. These results indicated that peripheral group II mGluR activation inhibited the functional activity of P2X3 receptors via a Gi/o protein and cAMP/PKA signaling pathway in rat DRG neurons, which revealed a novel mechanism underlying analgesic effects of peripheral group II mGluRs. This article is part of the Special Issue on "Purinergic Signaling: 50 years".

[Properties of Biochars Prepared from Different Crop Straws and Leaching Behavior of Heavy Metals].

In this study, rice straw, soybean straw, wheat straw, and corn straw were chosen as raw materials, and biochars were prepared through the pyrolysis method at 550℃ under oxygen-limited conditions to investigate the physicochemical properties of biochars derived from the straws, the migration and transformation characteristics of heavy metals (HMs) (Cr, Ni, Cu, As, Cd, and Pb) after pyrolysis, and their leaching behaviors in different leaching solutions. The results showed that the physicochemical properties and elemental composition of the biochars were basically consistent. However, compared with that of biochars derived from other straws, biochar derived from wheat straw had a higher ash content (22.48%) and H/C radio (0.06). Meanwhile, biochar derived from corn straw had a smaller micropore volume (0.006 cm3·g-1) and a correspondingly smaller specific surface area (110.120 m2·g-1), which was consistent with the SEM image. After pyrolysis, the content of HMs (except Cd) increased by 14.04% to 410.81%, especially that of Cu and As. However, the content of Cd in soybean straw and corn straw decreased by 20.49% and 8.20% after pyrolysis, respectively, due to the low boiling point of Cd. Furthermore, most of the HMs (except Cd and Pb) tended to transform from unstable (acid-soluble/exchangeable and reducible forms) to stable forms (oxidizable and residual forms), implying that pyrolysis facilitated the stabilization of the HMs. The HMs in biochar were not leached or were leached in small amounts in ultra-pure water and buffered salt solutions, as opposed to leaching in relatively larger amounts in acetic acid solution and humic acid solution. Cr and Ni showed low leaching capacity in all leaching solutions. Cu showed relatively high leaching capacity in acetic acid solution, with the leaching amount ranging from 2.601 mg·kg-1 to 4.224 mg·kg-1, and As showed a relatively high leaching capacity in humic acid solution, with the leaching amount ranging from 0.074 mg·kg-1to 0.166 mg·kg-1. After pyrolysis, the environmental quality index (PIi) and the Nemerow pollution index (NPI) values of various HMs increased by different degrees. However, the pollution of single HMs remained at a safe level, and the integrated pollution of biochars was at the level of "clean". Due to the significant increase in potential ecological risk factors (Er) of Ni, Cd, and Pb after pyrolysis, the potential ecological risk index (RI) of biochar derived from the rice straw increased slightly. However, the potential ecological risk indexes of biochars derived from other straws significantly decreased after pyrolysis, owing to the stabilization of HMs.

Secondary preventing effect of lung cancer in non-high-risk population: A retrospective investigation of opportunistic screening with low-dose computed tomography in Wuhan.

Background: Given the mortality benefit of low-dose computed tomography (LDCT) screening on high-risk populations, the retrospective investigation intended to identify the benefits of LDCT on lung cancer screening among the general demographic cohorts. Methods: We used an opportunistic screening with LDCT implemented during the pandemic in Wuhan to study the impact on subsequent thoracic surgeries, especially surgeries for lung cancer. Patients who received LDCT from October 1, 2019, to July 31, 2020, in three Triple-A accredited hospitals in Wuhan were included in the study. Relative week volumes of both surgeries before and after the chest LDCT screening were compared pairwise. The counts of surgeries for pulmonary nodules or masses, and corresponding pathological results among different gender and age groups were also compared. Result: The relative weekly volumes of thoracic surgery were significantly greater than those of stomach surgery after the opportunistic screening with LDCT. They were 33% (95% CI, 0.20-0.46; p<0. 001) higher than those of stomach surgery. For every 1,000 chest LDCT scans conducted in a given week, on average, 3.52(95% CI,0.56-6.49, p =0.03) thoracic surgeries were performed in the following week. After the implementation of opportunistic screening with LDCT, there was a higher percentage of young females with pulmonary nodule or mass (64.4% vs. 45.8%, p = 0.032). The fraction of lung cancer surgery in the treatment period was significantly greater than that in the control period (74.09% vs. 68.79%, p=0.007). There was a higher percentage of stage I lung cancer surgery in young and mid-age females than in the senior age group (64% vs. 53%, p= 0.05). Interpretation: Opportunistic screening with LDCT can advance the early diagnosis window of lung cancer in non-high-risk populations, especially young women who are easy to be ignored.

Stentless at ostium: a novel approach for treating ostial left anterior descending or left circumflex coronary artery lesions with drug-coated balloons.

BACKGROUND: Currently, there is no optimal treatment strategy for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. This study explored effectiveness and safety of drug-coated balloons (DCB) in individuals presenting with ostial LAD or LCx lesions. METHODS: A total of 137 patients with de novo ostial LAD or LCx lesions scheduled for DCB treatment were prospectively recruited into the study. After mandatory lesion preparation, DCB-only or hybrid strategy [DCB + drug-eluting stent (DES)] were performed on 120 patients (87.59%). The primary endpoint was the rate of 2-year target lesion revascularization (TLR). Rates of major adverse cardiovascular events (MACE), cardiac death, target vessel myocardial infarction (TVMI), and vessel thrombosis were explored as the secondary outcomes. Quantitative coronary angiography software was used to analyze coronary angiograms. RESULTS: Of the participants, 58 were treated with DCB-only and 62 with hybrid strategy. Relative to the DCB-only group, patients in the hybrid group had longer target lesions (15.47 ± 10.08 vs. 36.85 ± 9.46 mm, P<0.001) and higher Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) scores (23.47 ± 5.22 vs. 29.98 ± 3.18, P<0.001). During follow-up (731 ± 64 days), neither the primary endpoint (TLR) nor the secondary endpoints (including MACE, cardiac death, TVMI, and vessel thrombosis) differed statistically between the two groups (all P > 0.05). Treatment strategy (DCB-only or hybrid) was not a significant risk factor for TLR. Patients who underwent DCB-only exhibited less late lumen loss compared with the patients who underwent hybrid strategy (-0.26 ± 0.59 vs. 0.42 ± 0.47 mm, P<0.001) at 1-year angiographic follow-up. CONCLUSIONS: With regards to safety and efficacy, the strategy of DCB as a standalone therapy was similar in comparison with the hybrid strategy of DCB + DES for ostial LAD and ostial LCx lesions. This approach might be effective and technically easy in treating ostial LAD and LCx diseases.

Identifying potential microRNA biomarkers for colon cancer and colorectal cancer through bound nuclear norm regularization.

Colon cancer and colorectal cancer are two common cancer-related deaths worldwide. Identification of potential biomarkers for the two cancers can help us to evaluate their initiation, progression and therapeutic response. In this study, we propose a new microRNA-disease association identification method, BNNRMDA, to discover potential microRNA biomarkers for the two cancers. BNNRMDA better combines disease semantic similarity and Gaussian Association Profile Kernel (GAPK) similarity, microRNA function similarity and GAPK similarity, and the bound nuclear norm regularization model. Compared to other five classical microRNA-disease association identification methods (MIDPE, MIDP, RLSMDA, GRNMF, AND LPLNS), BNNRMDA obtains the highest AUC of 0.9071, demonstrating its strong microRNA-disease association identification performance. BNNRMDA is applied to discover possible microRNA biomarkers for colon cancer and colorectal cancer. The results show that all 73 known microRNAs associated with colon cancer in the HMDD database have the highest association scores with colon cancer and are ranked as top 73. Among 137 known microRNAs associated with colorectal cancer in the HMDD database, 129 microRNAs have the highest association scores with colorectal cancer and are ranked as top 129. In addition, we predict that hsa-miR-103a could be a potential biomarker of colon cancer and hsa-mir-193b and hsa-mir-7days could be potential biomarkers of colorectal cancer.

A1 Adenosine Receptor Activation Inhibits P2X3 Receptor-Mediated ATP Currents in Rat Dorsal Root Ganglion Neurons.

Purinergic signaling is involved in multiple pain processes. P2X3 receptor is a key target in pain therapeutics, while A1 adenosine receptor signaling plays a role in analgesia. However, it remains unclear whether there is a link between them in pain. The present results showed that the A1 adenosine receptor agonist N6-cyclopentyladenosine (CPA) concentration dependently suppressed P2X3 receptor-mediated and α,ß-methylene-ATP (α,ß-meATP)-evoked inward currents in rat dorsal root ganglion (DRG) neurons. CPA significantly decreased the maximal current response to α,ß-meATP, as shown a downward shift of the concentration-response curve for α,ß-meATP. CPA suppressed ATP currents in a voltage-independent manner. Inhibition of ATP currents by CPA was completely prevented by the A1 adenosine receptor antagonist KW-3902, and disappeared after the intracellular dialysis of either the Gi/o protein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, or the cAMP analog 8-Br-cAMP. Moreover, CPA suppressed the membrane potential depolarization and action potential bursts, which were induced by α,ß-meATP in DRG neurons. Finally, CPA relieved α,ß-meATP-induced nociceptive behaviors in rats by activating peripheral A1 adenosine receptors. These results indicated that CPA inhibited the activity of P2X3 receptors in rat primary sensory neurons by activating A1 adenosine receptors and its downstream cAMP signaling pathway, revealing a novel peripheral mechanism underlying its analgesic effect.

Potentiation of ASIC currents by lysophosphatidic acid in rat dorsal root ganglion neurons.

Lysophosphatidic acid (LPA) is a phospholipid which has been implicated in pain. Acid-sensing ion channels (ASICs) are important players in pain associated with tissue acidification. However, it is still unclear whether there is a link between LPA signaling and ASICs in pain processes. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pre-application of LPA enhanced ASIC-mediated and acid-evoked inward currents in a concentration-dependent manner. LPA shifted the concentration-response curve for protons upwards, with an increase of 41.79 ± 4.71% in the maximal current response of ASICs to protons in the presence of LPA. Potentiation of ASIC currents by LPA was blocked by the LPA1 receptor antagonist Ki16198, but not by the LPA2 receptor antagonist H2L5185303. The LPA-induced potentiation was also prevented by intracellular application of either G protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. LPA also enhanced ASIC3 currents in CHO cells co-expressing ASIC3 and LPA1 receptors, but not in cells expressing ASIC3 alone. Moreover, LPA increased the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, LPA exacerbated acid-induced nociceptive behaviors in rats. These results suggested that LPA enhanced ASIC-mediated electrophysiological activity and nociception via a LPA1 receptor and its downstream PKC rather than Rho signaling pathway, which provided a novel peripheral mechanism underlying the sensitization of pain.

Nasal carriage of CTX-M-55-producing Escherichia coli ST8369 in a healthy cohort in the city of Yangzhou, China.

This study aimed to investigate the prevalence and diversity of extended-spectrum ß-lactamases (ESBL)-producing Escherichia coli isolates from healthy individuals in a community and to elucidate their dissemination mechanism. Cefotaxime-resistant E. coli were isolated from 95 samples of healthy persons from one community in Yangzhou, China, and were tested for minimal inhibitory concentrations of 14 antimicrobial agents. The isolates were subjected to whole genome sequencing by Illumina Hiseq or PacBio single-molecule real-time sequencing. A total of 30 cefotaxime-resistant E. coli isolates were obtained, carrying bla CTX-M (n=29) or bla DHA (n=1), of which the bla CTX-M-55 (n=19) was the most predominant genotype. One novel bla CTX-M variant bla CTX-M-252 was identified. Thirteen CTX-M-55-producing E. coli isolates belonged to ST8369 from nasal (n=12) or faecal (n=1) samples shared the identical cgMLST type, resistance profiles, resistance genes, plasmid replicons, and a 5,053-bp bla CTX-M-55 structure ΔIS26-ΔISEcp1-bla CTX-M-55-Δorf477-ΔTn2. The bla CTX-M-55 gene was located on IncHI2/ST3 plasmid in E. coli ST8369. The lengths of bla CTX-M/bla DHA-carrying contigs in the remaining 17 E. coli strains ranged from 1,663 to 382,836 bp, located on chromosome (n=4) or plasmids (n=5); the location of the other eight contigs could not be determined due to incomplete assembly. The bla CTX-M was associated with ISEcp1 as previously reported. Nasal colonization of CTX-M-55-producing ST8369 E. coli strains has occurred among healthy individuals in one community. There is a potential risk of antimicrobial resistance dissemination between humans within one community through close contact or environment via aerosols or dust. Therefore, surveillance of nasal carriage of bla CTX-M in communities is warranted to further monitor the spread of the antimicrobial resistance genes in China.

Stereotactic Surgery for Treating Intractable Tourette Syndrome: A Single-Center Pilot Study.

To evaluate the potential effect of radiofrequency ablation and deep brain stimulation in patients with treatment-refractory Tourette syndrome (TS), this study enrolled thirteen patients with TS who were admitted to our hospital between August 2002 and September 2018. Four patients received a single- or multi-target radiofrequency ablation after local, potentiated, or general anesthesia; eight patients underwent deep brain stimulation (DBS) surgery; and one patient underwent both ablation and DBS surgery. The severity of tics and obsessive compulsive disorder symptoms and the quality of life were evaluated using the Yale Global Tic Severity Scale (YGTSS), Yale−Brown Obsessive Compulsive Scale (YBOCS), and Gilles de la Tourette Syndrome Quality of Life scale (GTS-QOL), respectively, before surgery, one month after surgery, and at the final follow-up after surgery, which was conducted in December 2018. A paired-sample t test and a multiple linear regression analysis were performed to analyze the data. All patients underwent the operation successfully without any severe complications. Overall, the YGTSS total scores at one month post-surgery (44.1 ± 22.3) and at the final visit (35.1 ± 23.7) were significantly decreased compared with those at baseline (75.1 ± 6.2; both p < 0.05). Additionally, the YBOCS scores at one month post-surgery (16.5 ± 10.1) and at the final visit (12.0 ± 9.5) were significantly decreased compared with those at baseline (22.5 ± 13.1; both p < 0.05). Furthermore, the GTS-QOL scores at one month post-surgery (44.0 ± 12.8) and at the final visit (31.0 ± 17.8) were significantly decreased compared with those at baseline (58.4 ± 14.2; both p < 0.05). Results from a multiple linear regression analysis revealed that the improvement in the YGTSS total score was independently associated with the improvement in the GTS-QOL score at one month post-surgery (standardized ß = 0.716, p = 0.023) and at the final visit (standardized ß = 1.064, p = 0.000). Conversely, changes in YBOCS scores did not correlate with changes in GTS-QOL scores (p > 0.05). Our results demonstrate that tics, psychiatric symptoms, and the quality of life in patients with intractable TS may be relieved by stereotactic ablation surgery and deep brain stimulation. Furthermore, it appears that the improvement in tics contributes more to the post-operative quality of life of patients than does the improvement in obsessive compulsive symptoms.

Enhancement of P2X3 Receptor-Mediated Currents by Lysophosphatidic Acid in Rat Primary Sensory Neurons.

Lysophosphatidic acid (LPA), a lipid metabolite, plays a role in both neuropathic and inflammatory pain through LPA1 receptors. P2X3 receptor has also been shown to participate in these pathological processes. However, it is still unclear whether there is a link between LPA signaling and P2X3 receptors in pain. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pretreatment of LPA concentration-dependently enhanced α,ß-methylene-ATP (α,ß-meATP)-induced inward currents mediated by P2X3 receptors. LPA significantly increased the maximal current response of α,ß-meATP, showing an upward shift of the concentration-response curve for α,ß-meATP. The LPA enhancement was independent on the clamping-voltage. Enhancement of P2X3 receptor-mediated currents by LPA was prevented by the LPA1 receptor antagonist Ki16198, but not by the LPA2 receptor antagonist H2L5185303. The LPA-induced potentiation was also attenuated by intracellular dialysis of either G-protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. Moreover, LPA significantly changed the membrane potential depolarization and action potential burst induced by α,ß-meATP in DRG neurons. Finally, LPA exacerbated α,ß-meATP- induced nociceptive behaviors in rats. These results suggested that LPA potentiated the functional activity of P2X3 receptors in rat primary sensory neurons through activation of the LPA1 receptor and its downstream PKC rather than Rho signaling pathway, indicating a novel peripheral mechanism underlying the sensitization of pain.