Objective To study the changes of connexin 32(Cx32) and Cx43 signals in the dorsal horn of spinal cord of rat with neuropathic pain induced by spared nerve injury(SNI) to sciatic nerve,and the analgeaic effect of 10μl carbenoxolone(CBX,a gap junction blocker,1mmol/L)on neuropathic pain via intrathecal administration. Methods Adult SD rats were randomly divided into 3 groups,normal group(the animals did not receive any treatment),sham group(incised the skin and only exposed the sciatic nerve) and the SNI group,exposed three branches of the sciatic nerve,i.e.the tibial nerve,the common peroneal nerve and the sural nerve,and cut the tibial nerve and the common peroneal nerve but remained sural nerve.The paw withdrawal mechanical threshold(PWMT) of normal,sham and SNI groups was measured at 1day before SNI and at 3,5,10,20 and 30 days after SNI,then the animals were killed and the spinal cords(L4-S1 segments) were removed and were used for Western blotting and anti-Cx32 and anti-Cx43 immunofluorescent staining.CBX was intrathecally injected at 20 days after SNI,and measured PWMT induced with an innocuous mechanical von Frey filaments stimulation. Results The PWMT of left behind leg in normal and sham groups did not reduce,while the left behind leg in SNI animals developed a conspicuous hypersensitivity to innocuous mechanical von Frey filaments stimulation.The PWMT of SNI rat decreased significantly as compared with normal and sham groups,and peaked at 20 days after SNI,it could maintain for as long as the animals were monitored.Anti-Cx32 and anti-Cx43 immunofluorescent reaction in the dorsal horn of spinal cord of SNI side increased significantly as compared with that in normal and sham group or the non-SNI side.After intrathecal injection of CBX 3hours,the PWMT of SNI side increased from the(2.5±1.0)g to(20.0±3.2)g,CBX inhibited the mechanical allodynia.In NS intrathecal injection group did not affect PWMT on SNI rats.Conclusion The gap junction plays an important role in the pathophysiologic process of chronic neuropathic pain.
This study aimed at investigating the clinical effect and safety of albumin binding paclitaxel (Nab-P) for the first-line treatment of advanced primary liver cancer. Clinical data of 23 patients with primary liver cancer, who were treated in the first-line tumor treatment Department in the PLA General Hospital from May 2014 to December 2015, were analyzed retrospectively. The patients were divided into an observation group and a control group, according to their treatment plan. The patients in the observation group (12) received Nab-P treatment (5 cases of Nab-P combined with tegeor, 5 cases of Nab-P combined with capecitabine, and 2 cases of Nab-P single drug), and the patients in the control group (11) received gemcitabine combined with oxaliplatin. Each treatment cycle lasted for 21 days, and the treatment effect was evaluated once every two cycles, while the adverse reactions were assessed after every cycle. The survival rates of the different groups were compared using the chi-square test or the Fisher's exact test, the Kaplan Meier survival curve, and the log rank test. Results from all patients were used to evaluate treatment efficacy and adverse reactions. In the observation group, there were 2 cases of partial remission, 7 cases of disease stability, and 3 cases of disease progress; in the control group, there were 2 cases of partial remission, 5 cases of disease stability, and 4 cases of disease progress. There was no significant difference in disease control rate between the two groups (75% vs. 64%, χ² = 0.350, P > 0.05). There was no significant difference in the median progression free survival time between the two groups (5.1 (2.7-6.7) months versus 4.3 (2.5-54) months, χ² =0.647, P > 0.05). No serious side effects were observed in any of the two groups. Among the observed side effects were some PLT toxicity and increased AST (Aspartate transaminase) incidence, which showed a statistically significant difference between the two groups (χ² = 5.490, P = 0.036 for PLT; χ² = 6.135, P = 0.027 for AST). The new Nab-P-based drug regimen has a good effect against primary liver cancer, and the side effects are tolerable. However, the sample size used in this study was small and further clinical studies using larger samples are required to verify the results.
OBJECTIVE To evaluate the expression of CXCR4 in oral squamous cell carcinoma (OSCC) and its influence on the proliferation of OSCC cells. METHODS The expression of CXCR4 was evaluated by immunohistochemical study in 91 surgically resected oral squamous cell carcinoma, and the relation between the staining and clinicopathological features was examined. Flow cytometry was used to detect CXCR4 expression in oral squamous cell carcinoma cell line. MTT assay was used to evaluate the SDF-1/CXCR4 influence on proliferation of tumor cells. RESULTS The expression of CXCR4 in OSCC was 62.6% and there was a significant association between the expression of CXCR4 and lymph node metastases (P < 0.05), tumor size (P < 0.01) and tumor histology grade (P < 0.01). In flow cytometry, a significant shift in fluorescent staining was seen in cells. In MTT assay, recombinant SDF-1 stimulated proliferation of OSCC cell and CXCR4 neutralization by monoclonal antibodies decreased proliferation. CONCLUSIONS The expression of CXCR4 was significantly correlated with the clinicopathological features and tumor proliferation. CXCR4 might be a valuable biomarker to predict the progression of OSCC.
Abstract Background Leading to a sustained epidemic spread with >2,000,000 confirmed human infections, including >100,000 deaths, COVID-19 was caused by SARS-CoV-2 and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of SARS-CoV-2 into the cell, contains two functional domains: an ACE2 receptor binding domain and a second domain necessary for fusion of the coronavirus and cell membranes. FURIN activity, exposes the binding and fusion domains, is essential for the zoonotic transmission of SARS-CoV-2. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, FURIN enzyme and ACE2 receptor were expressed in airway epithelia, cardiac tissue, and enteric canals, which considered as the potential target organ of the virus. However, report about the expression of FURIN and ACE2 in oral tissues was limited. Methods In order to investigate the potential infective channel of new coronavirus in oral cavity, we analyze the expression of ACE2 and FURIN that mediate the new coronavirus entry into host cells in oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemical staining experiment was performed to confirm the expression of ACE2 and FURIN in the protein level. Results The bioinformatics results indicated the differential expression of ACE2 and FURIN on epithelial cells of different oral mucosal tissues and the proportion of FURIN-positive cells was obviously higher than that of ACE2-positive cells. IHC experiments revealed that both the ACE2-positive and FURIN-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, which further confirm the bioinformatics results. Conclusions Based on these findings, we speculated that SARS-CoV-2 could effectively invade oral mucosal cells though two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by FURIN protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.
Background: Early neurological improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue in a prospective cohort. Methods: In INTRECIS study, five centers were designed to consecutively collect the blood sample from enrolled patients. Enrolled patients with ENI and without ENI were matched by propensity score matching with the ratio of 1:1. Preset 49 biomarkers were measured through protein microarray analysis. Enrichment of Gene Ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers. Results: Of 358 patients, 19 occurred ENI, who were assigned as ENI group, while 19 matched patients without ENI were assigned as Non ENI group. A total of nine biomarkers were found different, among which levels of chemokine (C-C motif) ligand (CCL)-23, chemokine (C-X-C motif) ligand (CXCL)-12, insulin-like growth factor binding protein (IGFBP)-6, interleukin (IL)-5, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, plasminogen activator inhibitor (PAI)-1, platelet-derived growth factor (PDGF)-AA, suppression of tumorigenicity (ST)-2, and tumor necrosis factor (TNF)-α were higher in ENI group, compared with those in Non ENI group. Conclusions: Our finding found that serum levels of CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α at admission were associated with post-thrombolytic ENI in ischemic stroke. The role of these biomarkers warrant further investigation.
Abstract Background : To evaluate whether oral lichen planus (OLP) is a risk factor for peri-implant diseases (PIDs) with a systematic review and meta-analysis. Methods : Six electronic databases including Medline, Web of Science, etc. were searched. Included studies are observational human studies written in English. Population of interest were those with/without OLP who received dental implant treatment. Follow-up time after implantation is from one month to 20 years. The quality of the included literature regarding risk of bias and methodology was assessed with Newcastle-Ottawa Scale or the Agency for Healthcare Research and Quality. The data involving exposure (OLP), primary outcomes (implants having PIDs) and secondary outcomes (probing depth/PD, bleeding on probing/BOP and bone loss/BL) and potential confounders were extracted. Heterogeneity was assessed by I² tests. Dichotomous data were expressed as risk ratio (RR) and 95% confidence interval (CI) which were calculated with a fixed effect model. Results : Of 139 literatures, two studies were enrolled and evaluated as high quality, which totally contained 68 participants receiving 222 (OLP vs. non-OLP, 112 vs. 110) implants with 12 to 120-month follow-up time. Proportions of implants with PIDs between OLP and non-OLP groups were as follows: 19.6% (22/112) vs. 22.7% (25/110) for PIM; 17.0% (19/112) vs. 10.9% (12/110) for PI. Meta-analysis found no recognizable difference in number of implants with PIDs (PI: RR = 1.49, 95% CI 0.77-2.90, P = 0.24; PIM:RR = 0.88, 95% CI 0.53 -1.46, P = 0.61; PIDs: RR = 1.08, 95% CI 0.75 -1.55, P = 0.68) or BOP (RR = 0.90, 95% CI: 0.70-1.15, P = 0.40) between OLP and non-OLP groups. Conclusions : Available literature regarding the effects of OLP on PIDs remains very limited. Existing evidence seems not support OLP as a suspected risk factor for PIDs. Large-scale prospective trials are required to test the findings. Keywords : dental implants; peri-implant diseases; oral lichen planus; systematic review; meta-analysis.
Accumulating evidence indicates that oxidative stress plays a critical role in Parkinson's disease (PD). Our previous work has shown that 100 Hz electro-acupuncture (EA) stimulation at ZUSANLI (ST36) and SANYINJIAO (SP6) protects neurons in the substantia nigra pars compacta from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in male C57BL/6 mice, a model of PD. In the present study we administered 100 Hz EA stimulation at the two acupoints to MPTP-lesioned mice for 12 sessions starting from the day prior to the first MPTP injection. We found that in the striatum of MPTP treated mice 100 Hz EA stimulation effectively inhibited the production of hydrogen peroxide and malonaldehyde, and increased glutathione concentration and total superoxide dismutase activity through biochemical methods. However, it decreased glutathione peroxidase activity via biochemical analysis and did not affect the level of 1-methyl-4-phenylpyridinium in the striatum revealed by high performance liquid chromatography with ultraviolet detection. These data suggest that 100 Hz EA stimulation at ST36 and SP6 has antioxidative effects in the MPTP model of PD. This data, along with our previous work, indicates that 100 Hz EA stimulation at ST36 and SP6 protects the nigrostriatal system by multiple mechanisms including antioxidation and antiapoptosis, and suggests that EA stimulation is a promising therapy for treating PD.
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