Perfusion outcomes with near-infrared indocyanine green imaging system in laparoscopic total mesorectal excision for mid-rectal or low-rectal cancer (POSTER): a study protocol.

INTRODUCTION: Anastomotic leakage (AL) is defined as the failure of complete healing or disruption of the anastomosis subsequent to rectal cancer surgery, resulting in the extravasation of intestinal contents into the intra-abdominal or pelvic cavity. It is a serious complication of rectal cancer surgery, accounting for a considerable increase in morbidity and mortality. The use of fluorescence imaging technology in surgery allows surgeons to better evaluate blood perfusion. However, the conclusions of some existing studies are not consistent, so a consensus on whether the near-infrared indocyanine green (NIR-ICG) imaging system can reduce the incidence of AL is needed. METHODS: This POSTER trial is designed as a multicentre, prospective, randomised controlled clinical study adhering to the "population, interventions, comparisons, outcomes (PICO)" principles. It is scheduled to take place from August 2019 to December 2024 across eight esteemed hospitals in China. The target population consists of patients diagnosed with rectal cancer through pathological confirmation, with tumours located≤10 cm from the anal verge, eligible for laparoscopic surgery. Enrolled patients will be randomly assigned to either the intervention group or the control group. The intervention group will receive intravenous injections of ICG twice, with intraoperative assessment of anastomotic blood flow using the near-infrared NIR-ICG system during total mesorectal excision (TME) surgery. Conversely, the control group will undergo conventional TME surgery without the use of the NIR-ICG system. A 30-day follow-up period postoperation will be conducted to monitor and evaluate occurrences of AL. The primary endpoint of this study is the incidence of AL within 30 days postsurgery in both groups. The primary outcome investigators will be blinded to the application of ICG angiography. Based on prior literature, we hypothesise an AL rate of 10.3% in the control group and 3% in the experimental group for this study. With a planned ratio of 2:1 between the number of cases in the experimental and control groups, and an expected 20% lost-to-follow-up rate, the initial estimated sample size for this study is 712, comprising 474 in the experimental group and 238 in the control group. ETHICS AND DISSEMINATION: This study has been approved by Ethics committee of Beijing Friendship Hospital, Capital Medical University (approval number: 2019-P2-055-02). The results will be disseminated in major international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04012645.

Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis.

Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10-3). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.

A theoretical study on the second-order nonlinear optical properties of Pt(II) bis-acetylide complexes: substituent and redox effects.

Density functional theory studies on the geometric and electronic structures, UV-vis absorption spectra, and second-order nonlinear optical (NLO) properties of four-coordinate Pt(II) bis-acetylide complexes, cis-[Pt(CNtBu)(ADC)(CCR)2] , have been employed. The effects of ligand variation and the single electron redox process on the structures and NLO response of complexes have also been investigated. It shows that the variations of the ligand and electron have little effect on the geometries of the complexes, but there is a significant effect on their electronic structures and NLO responses. The introduction of a single -NO2 group in acetylide ligands increases the first hyperpolarizability of complex 12 times, while one electron lost in five complexes enhances the first hyperpolarizability 496 times at the most. Both methods are considered effective ways for improving the NLO response of Pt(II) bis-acetylide complexes. Based on the analysis of the electronic and optical properties of fifteen studied complexes, the increase of NLO response is mainly ascribed to strong oscillator strengths, lower electron transition energy, and well-directed effective charge transfer. This work reveals some underlying relationships between the NLO responses and electronic structures of complexes, which is helpful for the design and synthesis of high-performance NLO materials of Pt(II) bis-acetylide complexes.

Fractionation, identification and umami characteristics of flavor peptides in natural brewed soy sauce.

To investigate the umami mechanisms and characteristics of soy sauce flavor peptides, four fractions from natural brewed soy sauce were separated using ultrafiltration and Sephadex G-15 gel filtration chromatography. Sensory and ligand-receptor interaction tests showed that the umami strengths of the fractions were related as follows: U1 > U2, G3 > G2, and G3 > U1. Peptide identification revealed that the < 550-Da peptides might be the major contributors to the umami taste of U1 and G3. The higher umami strength of G3 might be attributable to its higher content of umami peptides. G3's concentration-relative umami intensity curve was plotted using a two-alternative forced choice test. It was also revealed that less sourness, higher saltiness and cool (4 ℃) and hot (50 ℃) serving conditions were conductive to the umami perception of G3. The results could provide a reference for the application of soy-sauce flavor peptides in food.

Management and prediction of immune-related adverse events for PD1/PDL-1 immunotherapy in colorectal cancer.

Programmed cell death protein (PD-1) is an important immunosuppressive molecule, which can inhibit interaction between PD-1 and its ligand PD-L1, further enhancing the T cell response and anti-tumor activity, which is called immune checkpoint blockade. Immunotherapy, represented by immune checkpoint inhibitors, has opened up a new era of tumor treatment and is gradually being applied to colorectal cancer recently. Immunotherapy was reported could achieve a high objective response rate (ORR) for colorectal cancer with high microsatellite instability (MSI), thus opening up a new era of colorectal cancer immunotherapy. Along with the increasing use of PD1 drugs in colorectal cancer, we should pay more attention to the adverse effects of these immune drugs while seeing the hope. Immune-related adverse events (irAEs) caused by immune activation and immune homeostasis during anti-PD-1/PD-L1 therapy can affect multi-organ and even be fatal in serious cases. Therefore, understanding irAEs is essential for their early detection and appropriate management. In this article, we review the irAEs that occur during the treatment of colorectal cancer patients with PD-1/PD-L1 drugs, analyze the current controversies and challenges, and point out future directions that should be explored, including exploring efficacy predictive markers and optimizing the paradigm of individualized immunotherapy.

Ectopic expression of Nav1.7 in spinal dorsal horn neurons induced by NGF contributes to neuropathic pain in a mouse spinal cord injury model.

Neuropathic pain (NP) induced by spinal cord injury (SCI) often causes long-term disturbance for patients, but the mechanisms behind remains unclear. Here, our study showed SCI-induced ectopic expression of Nav1.7 in abundant neurons located in deep and superficial laminae layers of the spinal dorsal horn (SDH) and upregulation of Nav1.7 expression in dorsal root ganglion (DRG) neurons in mice. Pharmacologic studies demonstrated that the efficacy of the blood-brain-barrier (BBB) permeable Nav1.7 inhibitor GNE-0439 for attenuation of NP in SCI mice was significantly better than that of the BBB non-permeable Nav1.7 inhibitor PF-05089771. Moreover, more than 20% of Nav1.7-expressing SDH neurons in SCI mice were activated to express FOS when there were no external stimuli, suggesting that the ectopic expression of Nav1.7 made SDH neurons hypersensitive and Nav1.7-expressing SDH neurons participated in central sensitization and in spontaneous pain and/or walking-evoked mechanical pain. Further investigation showed that NGF, a strong activator of Nav1.7 expression, and its downstream JUN were upregulated after SCI in SDH neurons with similar distribution patterns and in DRG neurons too. In conclusion, our findings showed that the upregulation of Nav1.7 was induced by SCI in both SDH and DRG neurons through increased expression of NGF/JUN, and the inhibition of Nav1.7 in both peripheral and spinal neurons alleviated mechanical pain in SCI mice. These data suggest that BBB permeable Nav1.7 blockers might relieve NP in patients with SCI and that blocking the upregulation of Nav1.7 in the early stage of SCI via selective inhibition of the downstream signaling pathways of NGF or Nav1.7-targeted RNA drugs could be a strategy for therapy of SCI-induced NP.

Incidence and Risk Factors of Surgical Complications and Anastomotic Leakage After Transanal Total Mesorectal Excision for Middle and Low Rectal Cancer.

PURPOSE: Transanal total mesorectal excision (taTME) is a promising surgical procedure for middle and low rectal cancer; however, it is linked to significant morbidity. This study aimed to determine the incidence of postoperative surgical complications and anastomotic leakage following taTME and to identify their associated risk factors. METHODS: The prospective clinical data of 114 patients, who underwent taTME and primary anastomosis for mid-low rectal cancer between November 2016 and June 2022, were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinical characteristics and risk factors for predicting surgical complications and anastomotic leakage. RESULTS: Surgical complications occurred in 40 (35.1%) patients within the first 30 days following surgery. Based on the Clavien-Dindo classification, minor complications (Clavien-Dindo grades I + II) accounted for 30.7%, while major complications (Clavien-Dindo grades III + IV) accounted for only 4.4%. None of the patients died within 30 days. The incidence of anastomotic leakage was 15.8%: 4.4% as grade A (5 cases), 9.6% as grade B (11 cases), and 1.8% as grade C (2 cases). Preoperative T3-4 was identified as an independent risk factor for surgical complications (p = 0.031) by multivariate analysis. American Society of Anesthesiology score ≥ 3 (P = 0.021) and incomplete total mesorectal excision specimens (P = 0.030) were significantly associated with the risk of anastomotic leakage. CONCLUSIONS: In this study, the incidence of surgical complications and anastomotic leakage in taTME aligned with previously reported rates. Preoperative T3-4 was significantly associated with surgical complications. American Society of Anesthesiology score ≥ 3 and incomplete TME specimens independently increased the risk of anastomotic leakage.

Design of Airborne Large Aperture Infrared Optical System Based on Monocentric Lens.

Conventional reconnaissance camera systems have been flown on manned aircraft, where the weight, size, and power requirements are not stringent. However, today, these parameters are important for unmanned aerial vehicles (UAVs). This article provides a solution to the design of airborne large aperture infrared optical systems, based on a monocentric lens that can meet the strict criteria of aerial reconnaissance UAVs for a wide field of view (FOV) and lightness of airborne electro-optical pod cameras. A monocentric lens has a curved image plane, consisting of an array of microsensors, which can provide an image with 368 megapixels over a 100° FOV. We obtained the initial structure of a five-glass (5GS) asymmetric monocentric lens with an air gap, using ray-tracing and global optimization algorithms. According to the design results, the ground sampling distance (GSD) of the system is 0.33 m at 3000 m altitude. The full-field modulation transfer function (MTF) value of the system is more than 0.4 at a Nyquist frequency of 70 lp/mm. We present a primary thermal control method, and the image quality was steady throughout the operating temperature range. This compactness and simple structure fulfill the needs of uncrewed airborne lenses. This work may facilitate the practical application of monocentric lens in UAVs.

Prognostic nutrition index predicts short-term surgical complications in patients with rectal cancer after laparoscopic surgery.

Purpose: Surgical complications following laparoscopic rectal cancer surgery remain a major clinical problem. The prognostic nutritional index (PNI) is reportedly associated with postoperative outcomes. We aimed to evaluate the correlation between PNI and short-term surgical complications in patients with rectal cancer after laparoscopic surgery. Methods: The prospective clinical data of 225 patients with rectal cancer receiving laparoscopic surgery between January 2021 and April 2022 were retrospectively analyzed. The cut-off values and diagnostic accuracy of PNI preoperatively and on postoperative day (POD) 1 were determined using receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were performed to identify clinical characteristics and risk factors for surgical complications. Results: In total, 81 (36.0%) patients developed surgical complications. The optimal cut-off value for preoperative PNI was 40.15, and that for PNI on POD 1 was 35.28. The DeLong test found no statistically between-group difference in the area under the ROC curve (P = 0.598). Multivariate analysis identified that a preoperative PNI ≤40.15 [odds ratio (OR): 2.856, 95% confidence interval (CI): 1.287-6.341, P = 0.010] and PNI on POD 1 ≤35.28 (OR: 2.773, 95% CI: 1.533-5.016, P = 0.001) were independent risk factors for surgical complications. Patients with a preoperative PNI ≤40.15 or PNI on POD 1 ≤35.28 were more likely to have surgical complications after laparoscopic surgery for rectal cancer (61.1% vs. 31.2%, P = 0.001; 53.0% vs. 28.9%, P = 0.001). Conclusion: Preoperative and POD 1 PNI were independent predictors of short-term surgical complications after laparoscopic surgery for rectal cancer.

The taTME learning curve for mid-low rectal cancer: a single-center experience in China.

PURPOSE: As transanal total mesorectal excision (taTME) is performed worldwide, the optimization of existing training and guidance programs to enhance new taTME learners' competence in performing this procedure is warranted. This study aimed to evaluate the taTME learning curve in patients with mid-low rectal cancer. METHODS: Patients who underwent taTME for mid-low rectal cancer between October 2015 and August 2021 at a single center were included. A cumulative sum (CUSUM) learning curve analysis was performed with the total operation time as the study outcome. The learning curve was analyzed using risk-adjusted CUSUM analysis, with postoperative complications and anastomotic leakage (AL) as outcomes. RESULTS: In total, 104 consecutive patients were included in this study. The CUSUM learning curve for total operative time started declining after 42 cases (309.1 ± 84.4 vs. 220.2 ± 46.4, P < 0.001). The risk-adjusted CUSUM (RA-CUSUM) learning curve for postoperative complications fluctuated in cases 44-75 and declined significantly after case 75. The RA-CUSUM learning curve for AL declined after 68 cases. CONCLUSIONS: taTME had learning curves of 42, 75, and 68 cases for total operative time, postoperative complications, and AL, respectively. A surgeon may require 42 and 75 cases to achieve "proficiency" and "mastery" in taTME procedures, respectively.

Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer.

Immunotherapies, especially the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, have revolutionized the therapeutic strategies of various cancers. As for colorectal cancer (CRC), the current clinical application of PD-1/PD-L1 inhibitors are mainly used according to the mutation pattern, which is categorized into deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI-H) and proficient mismatch repair (pMMR), or non-high levels of microsatellite instability (non-MSI-H). PD-1/PD-L1 inhibitors have been proven to have favorable outcomes against dMMR/MSI-H CRC because of more T-cell infiltration into tumor tissues. Nevertheless, the effectiveness of PD-1/PD-L1 inhibitors in pMMR/non-MSI-H CRC is still uncertain. Because of the quite-lower proportion of dMMR/MSI-H in CRC, PD-1/PD-L1 inhibitors have been reported to combine with other antitumor treatments including chemotherapy, radiotherapy, and targeted therapy for better therapeutic effect in recent clinical trials. Neoadjuvant therapy, mainly including chemotherapy and radiotherapy, not only can reduce clinical stage but also benefit from local control, which can improve clinical symptoms and the quality of life. Adding immunotherapy into neoadjuvant therapy may change the treatment strategy of primary resectable or some metastatic CRC. In this review, we focus on the development of neoadjuvant anti-PD-1/PD-L1 therapy and discuss the future perspectives in CRC.

Abdomen anatomic characteristics on CT scans as predictive markers for short-term complications following radical resection of colorectal cancer.

Background: Prediction and management of short-term postoperative complications in patients with colorectal cancer are essential in postoperative rehabilitation. Through CT scan images, we can easily measure some parameters of abdomen anatomic characteristics. This study aimed to assess whether there is a relationship between the abdomen anatomic characteristics and short-term postoperative complications. Materials and methods: We conducted a retrospective study. Eighty patients in each complication group and non-complication group were recruited with propensity score match. Demographics, perioperative laboratory results and surgical information were collected and compared between groups with univariate analysis. Significant elements were brought into subsequent logistic regression analysis and ROC analysis for further identification. Results: Univariate analysis showed that preoperative white blood cells, preoperative neutrophil counts, rectus abdominis thickness (RAT), subcutaneous fat thickness (SFT), and abdomen depth (AD) were significantly different between the complication group and non-complication group. Logistic regression analysis demonstrated that higher RAT (p = 0.002), SFT (p < 0.001) and AD (p < 0.001) independently predicted the incidence of short-term postoperative complications. Conclusions: In this study on patients undergoing radical resection of colorectal cancer, abdomen anatomic characteristics including higher RAT, SFT and AD are associated with an increased risk of short-term postoperative complications.

A Case of CD5-Positive Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type Secondary to Chronic Lymphedema.

ABSTRACT: Primary cutaneous lymphoma occurring at the site of lymphedema is a rare complication. A total of 13 cases of primary cutaneous lymphoma associated with chronic lymphedema have been reported in international studies. We reported a case of cutaneous diffuse large B-cell lymphoma (DLBCL) (leg type) secondary to chronic lymphedema of the lower limbs. Histopathology showed hyperkeratosis of epidermis, acanthosis, and significant edema in the superficial dermis, with diffuse mononuclear infiltration in the dermis. Immunohistochemical studies revealed the expression of CD5, CD20, Pax-5, Bcl-2, Bcl-6, MUM-1, c-myc, and Ki-67. Therefore, the diagnosis of cutaneous DLBCL (leg type) was made. The study further confirmed the association between lymphoma and lymphedema. Especially, it showed CD5 expression. CD5-positive DLBCLs is a specific subgroup of DLBCLs, only approximately 10% of DLBCLs express CD5.

Spinal Cord Stimulation and Treatment of Peripheral or Central Neuropathic Pain: Mechanisms and Clinical Application.

Spinal cord stimulation (SCS) as an evidence-based interventional treatment has been used and approved for clinical use in a variety of pathological states including peripheral neuropathic pain; however, until now, it has not been used for the treatment of spinal cord injury- (SCI-) induced central neuropathic pain. This paper reviews the underlying mechanisms of SCS-induced analgesia and its clinical application in the management of peripheral and central neuropathic pain. Evidence from recent research publications indicates that nociceptive processing at peripheral and central sensory systems is thought to be modulated by SCS through (i) inhibition of the ascending nociceptive transmission by the release of analgesic neurotransmitters such as GABA and endocannabinoids at the spinal dorsal horn; (ii) facilitation of the descending inhibition by release of noradrenalin, dopamine, and serotonin acting on their receptors in the spinal cord; and (iii) activation of a variety of supraspinal brain areas related to pain perception and emotion. These insights into the mechanisms have resulted in the clinically approved use of SCS in peripheral neuropathic pain states like Complex Regional Pain Syndrome (CRPS) and Failed Back Surgery Syndrome (FBSS). However, the mechanisms underlying SCS-induced pain relief in central neuropathic pain are only partly understood, and more research is needed before this therapy can be implemented in SCI patients with central neuropathic pain.

A duplex SYBR green I-based real-time polymerase chain reaction assay for concurrent detection of feline parvovirus and feline coronavirus.

Feline coronavirus (FCoV) contains two serotypes, feline enteric coronavirus (FECV) and Feline infectious peritonitis virus (FIPV). FECV and feline parvovirus (FPV) can cause similar clinical symptoms in cats, such as diarrhea. The objective of this study was to establish a duplex SYBR Green I-based quantitative polymerase chain reaction (qPCR) assay for rapid and simultaneous detection of FPV and FCoV. Two pairs of specific PCR primers were designed to target fragments of the VP2 gene of FPV and of the 5' UTR gene of FCoV, respectively. The assay distinguished between the two viruses based on the melting curves (melting temperatures 77.0 ± 0.5 °C [FPV] and 80.5 ± 0.5 °C [FCoV]). The minimum limits of FPV and FCoV detection were 4.74 × 101 copies/µL and 7.77 × 101 copies/µL, respectively. The assay showed excellent reproducibility and reliability, based on the mean coefficient of variation. In conclusion, this novel duplex SYBR Green I-based qPCR assay is sensitive and can specifically, reliably, and rapidly detect FPV and FCoV (co-)infections.

MicroRNA-96 is required to prevent allodynia by repressing voltage-gated sodium channels in spinal cord.

Voltage-gated sodium channels (Navs) 1.7, 1.8, and 1.9 are predominately expressed in peripheral sensory neurons and are critical for action potential propagation in nociceptors. Unexpectedly, we found that expression of SCN9A, SCN10A, SCN11A, and SCN2A, the alpha subunit of Nav1.7, Nav1.8, Nav1.9 and Nav1.2, respectively, are up-regulated in spinal dorsal horn (SDH) neurons of miR-96 knockout mice. These mice also have de-repression of CACNA2D1/2 in DRG and display thermal and mechanical allodynia that could be attenuated by intrathecal or intraperitoneal injection of Nav1.7 or Nav1.8 blockers or Gabapentin. Moreover, Gad2::CreERT2 conditional miR-96 knockout mice phenocopied global knockout mice, implicating inhibitory neurons; nerve injury induced significant loss of miR-96 in SDH GABAergic and Glutamatergic neurons in mice which negatively correlated to up-regulation of Nav1.7, Nav1.8, Nav1.9 and Scn2a, this dis-regulation of miR-96 and Navs in SDH neurons contributed to neuropathic pain which can be alleviated by intrathecal injection of Nav1.7 or Nav1.8 blockers. In conclusion, miR-96 is required to avoid allodynia through limiting the expression of VGCCs and Navs in DRG and Navs in SDH in naïve and nerve injury-induced neuropathic pain mice. Our findings suggest that central nervous system penetrating Nav1.7 and Nav1.8 blockers may be efficacious for pain relief.

Prolonged Analgesia by Spinal Cord Stimulation Following a Spinal Injury Associated With Activation of Adult Neural Progenitors.

OBJECTIVES: Responses of spinal progenitors to spinal cord stimulation (SCS) following spinal cord injury (SCI) in rats were assessed to reveal their potential contribution to SCS-induced analgesia. METHODS: Spinal epidural electrodes were implanted in rats at T12 rostral to a quadrant dorsal horn injury at T13. Further groups additionally received either a microlesion to the dorsolateral funiculus (DLF) or gabapentin (10 mg/kg). SCS was performed at 25 Hz for 10 minutes on day 4 (early SCS) and at 10 Hz for 10 minutes on day 8 (late SCS) after injury. Paw withdrawal threshold (PWT) was measured before injury, 30 minutes before or after SCS, and before cull on day 14, followed by immunostaining assessment. RESULTS: Paw withdrawal thresholds in uninjured animals (51.0 ± 4.0 g) were markedly reduced after SCI (17.3 ± 2.2 g). This was significantly increased by early SCS (38.5 ± 5.2 g, P < 0.01) and further enhanced by late SCS (50.9 ± 1.9 g, P < 0.01) over 6 days. Numbers of neural progenitors expressing nestin, Sox2, and doublecortin (DCX) in the spinal dorsal horn were increased 6 days after SCS by 6-fold, 2-fold, and 2.5-fold, respectively (P < 0.05 to 0.01). The elevated PWT evoked by SCS was abolished by DLF microlesions (48.9 ± 2.6 g vs. 19.0 ± 3.9 g, P < 0.01) and the number of nestin-positive cells was reduced to the level without SCS (P < 0.05). Gabapentin enhanced late SCS-induced analgesia from 37.0 ± 3.9 g to 54.0 ± 0.8 g (P < 0.01) and increased gamma-aminobutyric acid (GABA)-ergic neuronal marker vesicular GABA transporter-positive newborn cells 2-fold (P < 0.01). CONCLUSIONS: Spinal progenitor cells appear to be activated by SCS via descending pathways, which may be enhanced by gabapentin and potentially contributes to relief of SCI-induced neuropathic pain.

Dysregulated Expression of Long Noncoding RNAs in Endometriosis.

Endometriosis is a common debilitating gynecologic disease. Almost 10% of reproductive-age women are affected by this disease; they commonly suffer pelvic pain and/or infertility. Early diagnosis of this multifactorial disease remains difficult because its etiology is not clear and the early symptoms are nonspecific. In addition, many reproductive-age women are unwilling to undergo invasive laparoscopic surgery because of the possibility of decreasing fertility. Thus, identifying biomarkers for the early diagnosis of endometriosis a key focus of current research. Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts that have length of > 200 nucleotides and lack protein-coding ability but still influence gene expression in various ways. With advances in genome-wide analysis, researchers have determined that lncRNAs play an important role in many human diseases, particularly tumors. Moreover, the role of lncRNAs in the pathogenesis of endometriosis has been continually recognized. In this review, we discuss the status of current research on dysregulated lncRNAs and their roles in the pathogenesis of endometriosis. We aim to stimulate new investigations toward the identification of lncRNAs as biomarkers for the early diagnosis and therapy of this long-term gynecological disease.

Exogenous hydrogen sulfide prevents lipopolysaccharide-induced inflammation by blocking the TLR4/NF-κB pathway in MAC-T cells.

Mastitis impairs animal health and results in economic loss. Lipopolysaccharide (LPS) may cause immune response and inflammation in the bovine mammary gland. Hydrogen sulfide (H2S) is the third gasotransmitter that acts as an anti-inflammation regulator in many cells. Despite the importance of H2S in regulating inflammation, the effect and mechanism of exogenous H2S on LPS-induced inflammation in bovine mammary epithelial cells are unknown. In the present study, with NaHS as a donor of H2S, the bovine mammary epithelial cell line (MAC-T) was applied as an in vitro model to study the role of H2S on LPS-induced MAC-T cells. The results verified that the cell viability was diminished by LPS but restored by exogenous H2S at a physiologically relevant concentration (10 µM). Additionally, the production of H2S was mitigated in the LPS-induced MAC-T cells. Meanwhile, exogenous H2S decreased the intracellular ROS production and mRNA expression levels of the pro-inflammatory cytokines, TNF-α, IL-1ß, IL-8, and IL-6. Furthermore, exogenous H2S inhibited the mRNA expression of TLR4 and activation of NF-κB signaling pathway. In summary, exogenous H2S exerts anti-inflammatory effects through attenuating oxidative stress and blocking the TLR4/NF-κB pathway in the LPS-induced bovine mammary epithelial cells. Our findings might clarify new prophylactic approaches for mastitis.

Salmonella enterica serotype typhimurium and S. Stanley differ in genomic evolutionary patterns and early immune responses in human THP-1 cell line and CD14+ monocytes.

Salmonella Typhimurium and S. Stanley are the most prevalent serogroup B serovars to infect humans in Taiwan. The aim was to determine possible factors to influence the prevalence between S. Typhimurium and S. Stanley. Genotypes were determined by pulsed field gel electrophoresis (PFGE) analysis and the intracellular survival, phagocytosis, reactive oxygen species (ROS) production of human monocyte THP-1 cell and tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and IL-1ßexpression in peripheral blood CD14+ cells after infection were analyzed. 182 S. Stanley was clonal disseminated with main pulsotypes 2 from 2004 to 2007. Overall S. Typhimurium evolved more genotypes, while S. Stanley conserved in genotypes. Human blood CD14+ monocytes expressed TNF-α, IL-6 and IL-1ß differently among serovars and bacterial conditions (live vs. killed). Live S. Stanley and S. Typhimurium suppressed the TNF-α and IL-6 expression compared to killed bacteria. However, live S. Typhimurium stimulated more IL-1ß expression than the killed bacteria, but S. Stanley expressed similar IL-1ß levels in both conditions. Furthermore, S. Stanley and S. Typhimurium differed in intracellular survival in the THP-1 cells, an early decrease for S. Stanley, not for S. Typhimurium. Additionally, higher reactive oxygen species (ROS) production in THP-1 cells was found agsinst S. Stanley infection, not found in S. Typhimurium. However, some isolates of S. Stanley could recover from early loss to become more in the monocytes than S. Typhimurium. Difference in phagocytized number, intracellular survival, ROS production and IL-1ß expression may contribute to prevalence different between two serovars.