Air embolism caused by peripheral superficial vein catheterization: A case report.

BACKGROUND: Air embolization is usually an iatrogenic complication that can occur in both veins and arteries. Intravenous air embolization is mainly associated with large central vein catheters and mechanical ventilation. A 59-year-old woman was sent to our hospital with spontaneous cerebral hemorrhage and treated conservatively with a left forearm peripheral venous catheter infusion drug. After 48 hours, the patient's oxygen saturation decreased to 92 % with snoring breathing. Computer tomography of the head and chest revealed scattered gas in the right subclavian, the right edge of the sternum, the superior vena cava, and the leading edge of the heart shadow. METHODS: She was sent to the intensive care unit for high-flow oxygen inhalation and left-side reclining instantly. As the patient was at an acute stage of cerebral hemorrhage and did not take the Trendelenburg position. RESULTS: The computed tomography (CT) scan after 24 hours shows that the air embolism subsides. CONCLUSION SUBSECTIONS: Air embolism can occur in any clinical scenario, suggesting that medical staff should enhance the ability to identify and deal with air embolism. For similar cases in clinical practice, air embolism can be considered.

Efficacy of Fire-Needle Therapy in Improving Neurological Function Following Cerebral Infarction and Its Effect on Intestinal Flora Metabolites.

Objective: This study was to investigate the mechanism of action and clinical efficacy of fire-needle therapy in improving neurological function in patients with acute cerebral infarction (identified as a wind-phlegm-blood stasis syndrome in traditional Chinese medicine). Methods: We included patients diagnosed with acute cerebral infarction (wind-phlegm-blood stasis syndrome) admitted to the Encephalopathy and Acupuncture Center of the Second Affiliated Hospital of Tianjin University of Chinese Medicine. We randomly allocated them into the treatment and control groups, with 45 cases in each group. Acupuncture treatments that focused on regulating the mind and dredging the collaterals were used in the control group, while the treatment group additionally received fire-needle therapy. Our indicators included the National Institutes of Health Stroke Scale (NIHSS) scores, the Fugl-Meyer Assessment (FMA) scale, peripheral blood tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), hypersensitivity C-reactive protein (hs-CRP), and intestinal metabolites short-chain fatty acids (SCFAs). We measured these indicators before treatment and 14 days after treatment. Results: The post-treatment NIHSS scores of the two groups were significantly reduced (P < 0.05), and the treatment group showed a more significant decline in the score when compared to the control group (P < 0.05). The treatment group showing significant improvement in the domains of reflex activity, mobility, cooperative movement, and finger movement (P < 0.05). Both groups showed a significant decrease in the IL-17 and hs-CRP levels (P < 0.05), with the treatment group demonstrating a significant declining trend when compared to the control group (P < 0.05). The levels of acetic acid, propionic acid, butyric acid, and valeric acid all increased significantly in the two groups (P < 0.05), with acetic acid and butyric acid increasing significantly in the treatment group when compared to the control group (P < 0.05). Clinical efficacy rate: 78.6% of patients in the treatment group had an excellent rate, whereas it was 30.0% in the control group, and the difference was statistically significant (P < 0.001). Conclusion: Fire-needle therapy was effective in upregulating the SCFA content in patients with acute cerebral infarction (wind-phlegm-blood stasis syndrome), inhibiting the level of the inflammatory response, and improving the recovery of neurological functions. Clinical registration number: Registration website link: https://www.chictr.org.cn. Registration date: 2022/9/27. Registration number: ChiCTR2200064122.

Preparation, characterization and protective effect of chitosan - Tripolyphosphate encapsulated dihydromyricetin nanoparticles on acute kidney injury caused by cisplatin.

Dihydromyricetin (DMY) is a natural dihydroflavonol compound known for its diverse pharmacological benefits. However, its limited stability and bioavailability posed significant challenges for further applications. To address these issues, in this study, an ion crosslinking method was utilized to prepare chitosan nanoparticles that were loaded with DMY. The synthesized chitosan nanoparticles (CS-DMY-NPs) were spherical in shape with particle size and ζ potential of 198.7 nm and 45.05 mV, respectively. Furthermore, in vitro release experiments demonstrated that CS-DMY-NPs had sustained release and protective effects in simulated gastric and intestinal fluids. CS-DMY-NPs exhibited better antioxidant activity by ABTS and DPPH radical scavenging activity than free DMY. In vivo study showed that CS-DMY-NPs alleviated cisplatin-induced kidney damage by inhibiting oxidative stress and proinflammatory cytokines, and had better activity compared to DMY (free). Immunofluorescence data showed that CS-DMY-NPs activated the Nrf2 signaling pathways in a dose-dependent manner to combat cisplatin-induced kidney damage. Our results demonstrate that CS-TPP has good compatibility with DMY, and CS-DMY-NPs exhibited better protective effects against cisplatin-induced acute kidney injury (AKI) than free DMY.

Design, synthesis, and biological evaluation of acyl sulfonamide derivatives with spiro cycles as NaV1.7 inhibitors for antinociception.

Chronic pain, as an unmet medical need, severely impacts the quality of life. The voltage-gated sodium channel NaV1.7 preferentially expressed in sensory neurons of dorsal root ganglia (DRG) serves a promising target for pain therapy. Here, we report the design, synthesis, and evaluation of a series of acyl sulfonamide derivatives targeting Nav1.7 for their antinociceptive activities. Among the derivatives tested, the compound 36c was identified as a selective and potent NaV1.7 inhibitor in vitro and exhibited antinociceptive effects in vivo. The identification of 36c not only provides a new insight into the discovery of selective NaV1.7 inhibitors, but also may hold premise for pain therapy.

Investigating the adverse outcome pathways (AOP) of neurotoxicity induced by DBDPE with a combination of in vitro and in silico approaches.

Current studies have shown an association between DBDPE and neurotoxicity. In this study, the adverse outcome pathway (AOP) and mechanistic analysis of DBDPE-induced neurotoxicity were explored by a combination of in vitro and in silico approaches in SK-N-SH cells. DBDPE-induced oxidative stress caused DNA strand breaks, resulting in the activation of poly (ADP-ribose) (PAR) polymerase-1 (PARP-1). Activation of PARP1 could cause toxic damage in various organ systems, especially in the nervous system. DBDPE-induced apoptosis via the caspase-dependent intrinsic mitochondrial pathway and the PARP1-dependent pathway. Activation of PARP1 by DBDPE was deemed the initiating event, thereby affecting the key downstream biochemical events (e.g., ROS production, DNA damage, membrane potential changes, and ATP reduction), which induced apoptosis. Furthermore, excessive activation of PARP1 was accompanied by the translocation of the apoptosis-inducing factor (AIF), which was associated with PARP1-dependent cell death. The inhibition of PARP1 by PJ34 reduced DBDPE-induced apoptosis and maintained cellular ATP levels. PJ34 also prevented the translocation of AIF from the mitochondria to the nucleus. These findings improve the understanding of the mechanism of DBDPE-induced neurotoxic effects and provide a theoretical basis for the ecological risk of DBDPE.

DBDPE and ZnO NPs synergistically induce neurotoxicity of SK-N-SH cells and activate mitochondrial apoptosis signaling pathway and Nrf2-mediated antioxidant pathway.

Decabromodiphenyl ethane (DBDPE), a new brominated flame retardant, could negatively affect neurobehavior and pose health risks to humans. Humans are also exposed to widely used nanomaterials. This study investigated the combined toxic effects and action types of DBDPE and Zinc oxide nanoparticles (ZnO NPs) on human neuroblastoma SK-N-SH cells and the toxicity mechanisms. DBDPE inhibited the viability of SK-N-SH cells by 21.87% at 25 mg/L. ZnO NPs synergistically exacerbated the toxic effects of DBDPE. DBDPE and ZnO NPs caused excessive ROS production and inhibition of antioxidant enzyme (SOD and GSH) activity in cells, thus causing oxidative cellular damage. Moreover, DBDPE and ZnO NPs caused apoptosis by disrupting mitochondrial kinetic homeostasis, reducing mitochondrial membrane potential (MMP), increasing cytochrome C release and regulating Bax/Bcl-2 and Caspase-3 mRNA and protein expression. DBDPE and ZnO NPs increased the mRNA expression of nuclear factor erythroid 2- related factor (Nrf2) and its downstream genes. The molecular mechanisms revealed that oxidative stress, apoptosis and mitochondrial dysfunction were the critical factors in combined cytotoxicity. The bioinformatics analysis further indicated that co-exposure affected Nrf2 activation, apoptotic factors expression and mitochondrial fusion. The findings enrich the risk perception of neurotoxicity caused by DBDPE and ZnO NPs.

A Rapid and Simple Method for DNA Preparation of Magnaporthe oryzae from Single Rice Blast Lesions for PCR-Based Molecular Analysis.

Rice blast is one of the most destructive diseases of rice worldwide, and the causative agent is the filamentous ascomycete Magnaporthe oryzae. With the successful cloning of more and more avirulence genes from M. oryzae, the direct extraction of M. oryzae genomic DNA from infected rice tissue would be useful alternative for rapid monitoring of changes of avirulence genes without isolation and cultivation of the pathogen. In this study, a fast, low-cost and reliable method for DNA preparation of M. oryzae from a small piece of infected single rice leaf or neck lesion was established. This single step method only required 10 min for DNA preparation and conventional chemical reagents commonly found in the laboratory. The AvrPik and AvrPi9 genes were successfully amplified with the prepared DNA. The expected DNA fragments from 570 bp to 1,139 bp could be amplified even three months after DNA preparation. This method was also suitable for DNA preparation from M. oryzae strains stored on the filter paper. All together these results indicate that the DNA preparation method established in this study is reliable, and could meet the basic needs for polymerase chain reaction-based analysis of M. oryzae.

Wet End Chemical Properties of a New Kind of Fire-Resistant Paper Pulp Based on Ultralong Hydroxyapatite Nanowires.

In 2014, a new type of the fire-resistant paper based on ultralong hydroxyapatite (HAP) nanowires was reported by the author's research group, which had superior properties and promising applications in various fields, such as high-temperature resistance, fire retardance, heat insulation, electrical insulation, energy, environmental protection, and biomedicine. The wet end chemical properties of the fire-resistant paper pulp are very important for papermaking and mechanical performance of the paper, which play a guiding role in the practical production of the fire-resistant paper. In this paper, the wet end chemical properties of a new kind of fire-resistant paper pulp based on ultralong HAP nanowires are studied for the first time by focusing on the wet end chemical parameters, the effects of these parameters on the properties such as flocculation, retention, draining, and white water circulation of the fire-resistant paper pulp, and their effects on the properties of the as-prepared fire-resistant paper. The experimental results indicated that the wet end chemical properties of the new kind of fire-resistant paper pulp based on ultralong HAP nanowires were unique and entirely different from those of the traditional paper pulp based on plant fibers. The wet end chemical properties of the fire-resistant paper pulp were significantly influenced by the inorganic adhesive and its content, which affected the runnability of the paper machine and the properties of the as-prepared fire-resistant paper. The flocculation properties of the fire-resistant paper pulp based on ultralong HAP nanowires were affected by the conductivity and Zeta potential. The addition of the inorganic adhesive in the fire-resistant paper pulp based on ultralong HAP nanowires could significantly increase the conductivity of the fire-resistant paper pulp, reduce the particle size of paper pulp floccules, and increase the tensile strength of the fire-resistant paper. In addition, the fire-resistant paper pulp based on ultralong HAP nanowires in the presence of inorganic adhesive exhibited excellent antibacterial performance. This work will contribute to and accelerate the commercialization process and applications of the new type of the fire-resistant paper based on ultralong HAP nanowires.

Two novel lncRNAs AF111167.2 and AL162377.1 targeting miR-21-5p mediated down expression of SYDE2 correlates with poor prognosis and tumor immune infiltration of ccRCC.

Advanced clear cell Renal Cell Carcinoma (ccRCC) is notoriously known for its poor prognosis. Synapse defective protein 1 homolog 2 encoded by the SYDE2 gene is a Rho GTPase-activating protein whose functional tumorigenic significance is still unclear. Recent pan-cancer analysis using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) data showed the potential tumor-suppressing effects of SYDE2 in ccRCC. Subsequently, the TCGA, GTEx data, and human protein atlas were employed to assess the correlation between the SYDE2 expression, clinical data, and overall survival (OS) in ccRCC patients. Furthermore, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) contributing to SYDE2 down expression were identified by expression, relationship, and survival analysis. Eventually, two novel lncRNAs, AL162377.1 and AF111167.2, targeting the miR-21-5p axis, were identified in the SYDE2 upstream non-coding RNAs (ncRNAs)-related pathway in ccRCC. The expression level of SYDE2 highly depends on the tumor immune cell infiltration and immune checkpoint expression. In summary, these data demonstrated that lncRNAs/miRNAs-mediated down-regulation of SYDE2 is related to the tumor immune infiltration. Hence, giving an insight into the prognosis of ccRCC.

Identification of a Partial and Selective TRPV1 Agonist CPIPC for Alleviation of Inflammatory Pain.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, predominantly expressed in a subset of peripheral sensory neurons for pain signaling. Topical application of agonist capsaicin for desensitizing TRPV1 currents has been approved for relief of chronic pain. However, the potent TRPV1 capsaicin is not ingestible and even topical capsaicin causes common side effects such as skin irritation, swelling, erythema and pruritus, suggesting that a mild TRPV1 agonist might be helpful for reducing side effects while reliving pain. In this study, we reported on a partial and selective TRPV1 agonist 4-(5-chloropyridin-2-yl)-N-(1H-indazol-6-yl)piperazine-1-carboxamide named CPIPC that was modified based on targeting the residue Arg557, important for conversion between the channel antagonism and agonism. Whole-cell patch clamp recordings indicated a concentration-dependent activation of TRPV1 currents by CPIPC with an EC50 of 1.56 ± 0.13 µM. The maximum efficacy of CPIPC (30 µM) was about 60% of saturated capsaicin (10 µM). Repetitive additions of CPIPC caused TRPV1 current desensitization in both TRPV1-expressing HEK293 cells and dorsal root ganglion (DRG) sensory neurons. Oral administration of CPIPC dose-dependently alleviated inflammatory pain in mice. Further site-directed mutagenesis combined with molecular docking revealed that residue Arg557 is critical for TRPV1 activation by CPIPC. Taken together, we identified a novel partial and selective TRPV1 agonist CPIPC that exhibits antinociceptive activity in mice.

miR-9-5p promotes myogenic differentiation via the Dlx3/Myf5 axis.

MicroRNAs play an important role in myogenic differentiation, they bind to target genes and regulate muscle formation. We previously found that miR-9-5p, which is related to bone formation, was increased over time during the process of myogenic differentiation. However, the mechanism by which miR-9-5p regulates myogenic differentiation remains largely unknown. In the present study, we first examined myotube formation and miR-9-5p, myogenesis-related genes including Dlx3, Myod1, Mef2c, Desmin, MyoG and Myf5 expression under myogenic induction. Then, we detected the expression of myogenic transcription factors after overexpression or knockdown of miR-9-5p or Dlx3 in the mouse premyoblast cell line C2C12 by qPCR, western blot and myotube formation under myogenic induction. A luciferase assay was performed to confirm the regulatory relationships between not only miR-9-5p and Dlx3 but also Dlx3 and its downstream gene, Myf5, which is an essential transcription factor of myogenic differentiation. The results showed that miR-9-5p promoted myogenic differentiation by increasing myogenic transcription factor expression and promoting myotube formation, but Dlx3 exerted the opposite effect. Moreover, the luciferase assay showed that miR-9-5p bound to the 3'UTR of Dlx3 and downregulated Dlx3 expression. Dlx3 in turn suppressed Myf5 expression by binding to the Myf5 promoter, ultimately inhibiting the process of myogenic differentiation. In conclusion, the miR-9-5p/Dlx3/Myf5 axis is a novel pathway for the regulation of myogenic differentiation, and can be a potential target to treat the diseases related to muscle dysfunction.

Low doses of niclosamide and quinacrine combination yields synergistic effect in melanoma via activating autophagy-mediated p53-dependent apoptosis.

Malignant melanoma is a highly aggressive, malignant, and drug-resistant tumor. It lacks an efficient treatment approach. In this study, we developed a novel anti-melanoma strategy by using anti-tapeworm drug niclosamide and anti-malarial drug quinacrine, and investigated the molecular mechanism by in vitro and in vivo assays. Meanwhile, other types of tumor cells, immortalized epithelial cells and bone marrow mesenchymal stem cells were used to evaluate the universal role of anti-cancer and safety of the strategy. The results showed, briefly, an exposure to niclosamide and quinacrine led to an increased apoptosis-related protein p53, cleaved caspase-3 and cleaved PARP and autophagy-related protein LC3B expression, and a decreased expression of autophagy-related protein p62, finally leading to cell apoptosis and autophage. After inhibiting autophagy by Baf-A1, flow cytometry and western blot showed that the expression of apoptosis-related proteins was down-regulated and the number of apoptotic cells decreased. Subsequently, in the siRNA-mediated p53 knockdown cells, the expression of apoptosis-related proteins and the number of apoptotic cells were also reduced, while the expression of autophagy-related proteins including LC3B, p62 did not change significantly. To sum up, we developed a new, safe strategy for melanoma treatment by using low doses of niclosamide and quinacrine to treat melanoma; and found a novel mechanism by which the combination application of low doses of niclosamide and quinacrine exerts an efficient anti-melanoma effect through activation of autophagy-mediated p53-dependent apoptosis. The novel strategy was verified to exert a universal anti-cancer role in other types of cancer.

Streptococcus mutans-associated bacteria in dental plaque of severe early childhood caries.

BACKGROUND: Streptococcus mutans (S. mutans) is a potential pathogenic bacteria of dental caries. However, the level of S. mutans is low in some children with severe early childhood caries (SECC). AIM: To evaluate the effect of S. mutans level on dental microbiome and cariogenesis. METHODS: The oral microbiota was compared between caries-free group (CF) and SECC group.16S rRNA gene sequencing was used for S. mutans level bacterial community analysis. The candidate bacteria that were closely related with S. mutans abundance were identified and confirmed by absolute quantitative real-time PCR in clinical dental plaque samples from CF and SECC groups. RESULTS: Through in-depth analysis of dental plaque microorganism, Leptotrichia, Selenomonas and Prevotella_7 were found in the S. mutans-low group (p < 0.05) and Porphyromonas, Selenomonas_3 were found in the S. mutans-high group (p < 0.05). Through quantitative real-time PCR, Leptotrichia, Selenomonas and Prevotella_7 were identified as the potential biomarkers of SECC when S. mutans was at a low level. CONCLUSION: Leptotrichia, Selenomonas and Prevotella_7 are identified as potential biomarkers in SECC with a low abundance or without S. mutans. Our study may shed light on the understanding of caries occurrence in SECC with low abundance of S. mutans. ABBREVIATIONS: S. mutans, Streptococcus mutans; CF, caries-free; SECC, severe early childhood caries; ECC, early childhood caries; rRNA, ribosome RNA; qPCR, Quantitative real-time PCR; OTUs, operational taxonomic units; ANOVA, analysis of variance; LDA, Linear discriminant analysis; LEfSe, Linear discriminant analysis effect size; COG, Groups of proteins; NMDS, Non-MetricMulti-Dimensional Scaling; IL-1ß, interleukin -1ß; IL-6, interleukin-6; IL-8, interleukin-8; IL-10, interleukin-10.

DIC/Oxyma-based accelerated synthesis and oxidative folding studies of centipede toxin RhTx.

Coupling reagents play crucial roles in the iterative construction of amide bonds for the synthesis of peptides and peptide-based derivatives. The novel DIC/Oxyma condensation system featured with the low risk of explosion displayed remarkable abilities to inhibit racemization, along with efficient coupling efficiency in both manual and automated syntheses. Nevertheless, an ideal reaction molar ratio in DIC/Oxyma condensation system and the moderate reaction temperature by manual synthesis remain to be further investigated. Herein, the synthetic efficiencies of different reaction ratios between DIC and Oxyma under moderate reaction temperature were systematically evaluated. The robustness and efficiency of DIC/Oxyma condensation system are validated by the rapid synthesis of linear centipede toxin RhTx. Different folding strategies were applied for the construction of disulfide bridges in RhTx, which was further confirmed in assays of circular dichroism and patch-clamp electrophysiology evaluation. This work establishes the DIC/Oxyma-based accelerated synthesis of peptides under moderate condensation conditions, which is especially useful for the manual synthesis of peptides. Besides, the strategy presented here provides robust technical supports for the large-scale synthesis and oxidative folding of RhTx.

A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma.

SIMPLE SUMMARY: Clinically, aberrant lipid metabolism is responsible for overweight and/or obesity. Overweight is considered as an independent factor of cancer risk in 2019. Therefore, lipid metabolic reprogramming is an emerging hallmark of malignancy. It is an urgent need to comprehensively understand the relationship among lipid metabolism and HNSCC and identify a valuable biomarker for predicting prognosis of HNSCC patients. Three new findings were found in this study. Firstly, we identified the lipid-related differentially expressed genes (DEGs) by using the GEO microarrays and TCGA dataset. A novel lipid-related mRNA prognostic signature (LRPS, consisting of ADCY2, LIPE and OLR1) was developed, which could predict the survival and prognosis of HNSCC patients as an independent effective prognostic factor. Secondly, we found that the LRPS could indicate the type of infiltrated immune cells in HNSCC tumor microenvironment. Thirdly, we verified that the LPPS score could interpret the TP53 status of HNSCC. Our new findings indicated that LRPS has a potential to be a promising indicator of overall survival, TP53 status, and immune characteristics in HNSCC, and perhaps can monitor and guide the treatment efficacy and prognosis of HNSCC in the future. BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of lymph node metastasis and a high mortality. Lipid metabolic reprogramming is an emerging carcinogen as its role in fulfilling cancer growth and spread. However, little is known about the correlation between lipid metabolism and HNSCC. MATERIALS AND METHODS: Expressions of lipid-related genes were obtained from the Cancer Genome Atlas (TCGA) and Gene expression Omnibus (GEO) databases for differential and functional analyses. A total number of 498 patients from TCGA with complete information were included to identify a lipid-related prognostic signature (LRPS), based on ADCY2, LIPE, and OLR1, by using univariate and multivariate Cox regression analyses. LRPS-high and LRPS-low groups were accordingly divided to pathway and cell enrichment analyses. RESULTS: LRS-low patients had a better overall survival and relapse - free survival than LRS-high ones in HNSCC. The LRPS-high group was significantly related to perineural invasion of cancer, cancer-related pathways, high TP53 mutation rate, high proportion of natural killer T cells (NKT), dendritic cells, monocytes, Treg, and M1 and M2 macrophage infiltration in HNSCC tumor tissues. Conversely, the LRPS-low group correlated with DNA damage-related and T-cell-regulated pathways, low frequency of mutated TP53, and high infiltration of B cells and CD4+ effector cells including Th1 and Th2. CONCLUSION: LRPS has a potential to be a promising indicator of overall survival, prognosis, TP53 status, and immune characteristics in HNSCC.

Trigonal-Sparing vs. Trigonal-Involved OnabotulinumtoxinA Injection for the Treatment of Overactive Bladder: A Systematic Review and Meta-Analysis.

Objective: Overactive bladder (OAB) is a disease characterized by the presence of urinary urgency. We carried out a meta-analysis to assess the effectiveness and safety of trigonal-involved injection of onabotulinumtoxinA (BoNT-A) in comparison with the trigonal-sparing technique in cases with OAB [neurogenic detrusor overactivity (NDO) and idiopathic detrusor overactivity (IDO)]. Methods: Randomized controlled trials (RCTs) of BoNT-A injection for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The datum was calculated by RevMan version 5.3.0. The original references of relating articles were also reviewed. Results: In total, six RCTs involving 437 patients were included in our analysis. For OAB, the trigone-including group showed a different patient symptom score (p = 0.03), complete dryness rate (p = 0.002), frequency of incontinence episodes (p = 0.01), detrusor pressure at maximum flow rate (p = 0.01), and volume at the first desire to void (p = 0.0004) compared with the trigone-sparing group. Also, a trigone-including intradetrusor injection demonstrated a significant improvement in the patient symptom score (p = 0.0004), complete dryness rate (p = 0.0002), frequency of incontinence episodes (p = 0.0003), detrusor pressure at maximum flow rate (p = 0.01), and volume at the first desire to void (p = 0.00006) compared with the trigone-sparing group for treatment of NDO. The adverse events rates were similar in both groups. Conclusions: The meta-analysis has demonstrated that trigone-including BoNT-A injection was more effective compared with the trigone-sparing injection for the treatment of OAB, especially for NDO.

Curcumin inhibits the viability, migration and invasion of papillary thyroid cancer cells by regulating the miR-301a-3p/STAT3 axis.

Thyroid cancer is one of the most common malignant tumors, and the mortality rate associated with thyroid cancer has been increasing annually. Curcumin has been reported to exert an antitumor effect on papillary thyroid cancer (PTC), and the identification of additional mechanisms underlying the anticancer effect of curcumin on PTC requires further investigation. The present study aimed to explore the effects of curcumin on the viability, migration and invasion of PTC cells. TPC-1 cells were incubated with different concentrations of curcumin, and then, cell viability, migration and invasion, and wound healing were examined by CCK-8, Transwell and wound healing assays, respectively. Subsequently, microRNA (miR)-301a-3p mimics, miR-301a-3p inhibitors and signal transducer and activator of transcription (STAT)3 overexpression vector were transfected into TPC-1 cells, and cell viability, migration, and invasion were reassessed in these transfected cells. Matrix metallopeptidase (MMP)-2, MMP-9, epithelial-mesenchymal transition (EMT)-related markers, and Janus kinase (JAK)/STAT signaling pathway components were assessed by western blot analysis. Curcumin significantly inhibited cell viability, migration and invasion and downregulated MMP-2, MMP-9 and EMT marker expression. Additionally, curcumin decreased STAT3 expression by upregulating miR-301a-3p expression, and the inhibition of miR-301a-3p and the overexpression of STAT3 reversed the effects of curcumin on cell viability, migration and invasion, and MMP-2, MMP-9 and EMT marker expression in TPC-1 cells. Furthermore, curcumin suppressed the JAK/STAT signaling pathway through the miR-301a-3p/STAT3 axis. The data of the present study indicated that curcumin could inhibit the viability, migration and invasion of TPC-1 cells by regulating the miR-301a-3p/STAT3 axis. These findings may provide a possible strategy for the clinical treatment of PTC.

Inhibition of Nav1.7 channel by a novel blocker QLS-81 for alleviation of neuropathic pain.

Voltage-gated sodium channel Nav1.7 robustly expressed in peripheral nociceptive neurons has been considered as a therapeutic target for chronic pain, but there is no selective Nav1.7 inhibitor available for therapy of chronic pain. Ralfinamide has shown anti-nociceptive activity in animal models of inflammatory and neuropathic pain and is currently under phase III clinical trial for neuropathic pain. Based on ralfinamide, a novel small molecule (S)-2-((3-(4-((2-fluorobenzyl) oxy) phenyl) propyl) amino) propanamide (QLS-81) was synthesized. Here, we report the electrophysiological and pharmacodynamic characterization of QLS-81 as a Nav1.7 channel inhibitor with promising anti-nociceptive activity. In whole-cell recordings of HEK293 cells stably expressing Nav1.7, QLS-81 (IC50 at 3.5 ± 1.5 µM) was ten-fold more potent than its parent compound ralfinamide (37.1 ± 2.9 µM) in inhibiting Nav1.7 current. QLS-81 inhibition on Nav1.7 current was use-dependent. Application of QLS-81 (10 µM) caused a hyperpolarizing shift of the fast and slow inactivation of Nav1.7 channel about 7.9 mV and 26.6 mV, respectively, and also slowed down the channel fast and slow inactivation recovery. In dissociated mouse DRG neurons, QLS-81 (10 µM) inhibited native Nav current and suppressed depolarizing current pulse-elicited neuronal firing. Administration of QLS-81 (2, 5, 10 mg· kg-1· d-1, i.p.) in mice for 10 days dose-dependently alleviated spinal nerve injury-induced neuropathic pain and formalin-induced inflammatory pain. In addition, QLS-81 (10 µM) did not significantly affect ECG in guinea pig heart ex vivo; and administration of QLS-81 (10, 20 mg/kg, i.p.) in mice had no significant effect on spontaneous locomotor activity. Taken together, our results demonstrate that QLS-81, as a novel Nav1.7 inhibitor, is efficacious on chronic pain in mice, and it may hold developmental potential for pain therapy.