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1.
World J Clin Cases ; 11(33): 8003-8012, 2023 Nov 26.
Article in English | MEDLINE | ID: mdl-38075574

ABSTRACT

BACKGROUND: The recovery time of hand wounds is long, which can easily result in chronic and refractory wounds, making the wounds unable to be properly repaired. The treatment cycle is long, the cost is high, and it is prone to recurrence and disability. Double layer artificial dermis combined with autologous skin transplantation has been used to repair hypertrophic scars, deep burn wounds, exposed bone and tendon wounds, and post tumor wounds. AIM: To investigate the therapeutic efficacy of autologous skin graft transplantation in conjunction with double-layer artificial dermis in treating finger skin wounds that are chronically refractory and soft tissue defects that expose bone and tendon. METHODS: Sixty-eight chronic refractory patients with finger skin and soft tissue defects accompanied by bone and tendon exposure who were admitted from July 2021 to June 2022 were included in this study. The observation group was treated with double layer artificial dermis combined with autologous skin graft transplantation (n = 49), while the control group was treated with pedicle skin flap transplantation (n = 17). The treatment status of the two groups of patients was compared, including the time between surgeries and hospital stay. The survival rate of skin grafts/flaps and postoperative wound infections were evaluated using the Vancouver Scar Scale (VSS) for scar scoring at 6 mo after surgery, as well as the sensory injury grading method and two-point resolution test to assess the recovery of skin sensation at 6 mo. The satisfaction of the two groups of patients was also compared. RESULTS: Wound healing time in the observation group was significantly longer than that in the control group (P < 0.05, 27.92 ± 3.25 d vs 19.68 ± 6.91 d); there was no significant difference in the survival rate of skin grafts/flaps between the two patient groups (P > 0.05, 95.1 ± 5.0 vs 96.3 ± 5.6). The interval between two surgeries (20.0 ± 4.3 d) and hospital stay (21.0 ± 10.1 d) in the observation group were both significantly shorter than those in the control group (27.5 ± 9.3 d) and (28.4 ± 17.7 d), respectively (P < 0.05). In comparison to postoperative infection (23.5%) and subcutaneous hematoma (11.8%) in the control group, these were considerably lower at (10.2%) and (6.1%) in the observation group. When comparing the two patient groups at six months post-surgery, the excellent and good rate of sensory recovery (91.8%) was significantly higher in the observation group than in the control group (76.5%) (P < 0.05). There was also no statistically significant difference in two point resolution (P > 0.05). The VSS score in the observation group (2.91 ± 1.36) was significantly lower than that in the control group (5.96 ± 1.51), and group satisfaction was significantly higher (P < 0.05, 90.1 ± 6.3 vs 76.3 ± 5.2). CONCLUSION: The combination of artificial dermis and autologous skin grafting for the treatment of hand tendon exposure wounds has a satisfactory therapeutic effect. It is a safe, effective, and easy to operate treatment method, which is worthy of clinical promotion.

3.
Nat Commun ; 14(1): 1340, 2023 03 11.
Article in English | MEDLINE | ID: mdl-36906670

ABSTRACT

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.


Subject(s)
Bile Duct Neoplasms , Biliary Tract Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biliary Tract Neoplasms/drug therapy , Biliary Tract Neoplasms/pathology , Cisplatin/therapeutic use , Deoxycytidine/therapeutic use , Gemcitabine
4.
Mol Neurobiol ; 60(4): 2086-2098, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36602702

ABSTRACT

Central post-stroke pain (CPSP) is a highly refractory form of central neuropathic pain that has been poorly studied mechanistically. Recent observations have emphasized the critical role of the spinal dorsal horn in CPSP. However, the underlying mechanisms remain unclear. In this study, rats were subjected to thalamic hemorrhage to investigate the role of spinal monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine receptor 2 (CCR2) in the development of CPSP. Immunohistochemical staining and ELISA were used to assess the expression changes of c-Fos, Iba-1, GFAP, MCP-1, and CCR2 in the dorsal horn of the lumbar spinal cord following thalamic hemorrhage, and the involvement of spinal MCP-1 in CPSP was examined by performing intrathecal anti-MCP-1 mAb injection to neutralize the spinal extracellular MCP-1. We demonstrated that intra-thalamic collagenase microinjection induced persistent bilateral mechanical pain hypersensitivity and facilitated the spontaneous pain behaviors evoked by intraplantar bee venom injection. Accompanying CPSP, the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn was significantly increased up to 28 days post-intra-thalamic collagenase microinjection. Intrathecal injection of minocycline and fluorocitrate dramatically reverses the bilateral mechanical pain hypersensitivity. Moreover, intra-thalamic collagenase microinjection dramatically induced the up-regulation of MCP-1 but had no effect on the expression of CCR2 in the bilateral lumbar spinal dorsal horn, and MCP-1 was primarily localized in the neuron. Intrathecal injection of anti-MCP-1 mAb was also able to reverse CPSP and reduce the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn. These findings indicated that spinal MCP-1 contributes to CPSP by mediating the activation of spinal neurons and glial cells following thalamic hemorrhage stroke, which may provide insights into pharmacologic treatment for CPSP.


Subject(s)
Chemokine CCL2 , Neuralgia , Rats , Animals , Chemokine CCL2/metabolism , Central Nervous System Sensitization , Rats, Sprague-Dawley , Hyperalgesia/metabolism , Neuralgia/metabolism , Spinal Cord/metabolism , Spinal Cord Dorsal Horn/metabolism
5.
Front Immunol ; 13: 943066, 2022.
Article in English | MEDLINE | ID: mdl-36159865

ABSTRACT

Background: Immune checkpoint inhibitor (ICI)-combined chemotherapy in advanced intrahepatic cholangiocarcinoma has been proved to have more efficacy in a series of clinical trials. However, whether the tumor microenvironment (TME) plays a vital role in immune-combined therapy has not been rigorously evaluated. Methods: Firstly, we assayed the immunogenic properties of GEM-based chemotherapy. Then, 12 ICC patients treated with PD-1 inhibitor (sintilimab) combined with gemcitabine and cisplatin (GemCis) from a phase 2 clinical trial (ChiCTR2000036652) were included and their immune-related gene expression profiles were analyzed using RNA from baseline tumor samples. Immune-related signature correlating with clinical outcome was identified according to the 12 ICC patients, and its predictive value was validated in an ICC cohort with 26 patients. Multiplexed immunofluorescence (mIF) and flow cytometry (FCM) analysis were performed to evaluate the immune-related molecules with therapeutic outcomes. Results: GEM-based chemotherapy induced immunogenic cell death of cholangiocarcinoma cells, together with increased CD274 expression. In an ICC cohort, we found that upregulation of immune-checkpoint molecules and immune response-related pathways were significantly related to better clinical outcome. On the contrary, baseline immune-cell proportions in tumor tissues did not show any correlation with clinical benefit between responders and non-responders. Immune-related signature (including six genes) correlating with clinical outcome was identified according to the 12 ICC patients, and its predictive value was validated in a small ICC cohort with 26 patients. Conclusion: Immune-related RNA signature predicts the outcome of PD-1 inhibitor-combined GEMCIS therapy in advanced intrahepatic cholangiocarcinoma, which could be tested as a biomarker for immune-chemotherapy in the future.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/genetics , Bile Ducts, Intrahepatic/metabolism , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/genetics , Cholangiocarcinoma/metabolism , Cisplatin/therapeutic use , Clinical Trials, Phase II as Topic , Humans , Immune Checkpoint Inhibitors/therapeutic use , RNA , Tumor Microenvironment
6.
Ying Yong Sheng Tai Xue Bao ; 33(9): 2321-2330, 2022 Sep.
Article in Chinese | MEDLINE | ID: mdl-36131646

ABSTRACT

Crown width is a critical variable in reflecting the individual tree growth status and in developing forest growth and yield models. With the crown width base model as reference, we developed the crown width quantile regression models for different quantiles (0.50, 0.90, 0.93, 0.95, 0.96, 0.99) based on the data of 2763 Korean pines in 66 permanent plots from the 10-55 years old plantations in Dabiangou forest farm, mountainous areas of eastern Liaoning Province. We used the reparameterization method by introducing the single tree competition index (Rd) and used the dummy variable method by introducing stand density and forest layer variables. We then selected optimal quantile of maximum crown width in the stand by comparing our model developed routine to the traditional methods. The final crown width linear mixed effect quantile regression model was developed based on the optimal quantile at the plot level. The influence of each variable on crown width was analyzed to reflect the difference of crown width among individual trees in the stand. The models with different stand densities and forest layers had significant difference based on F statistical test: the Ra2 of the model increased by 0.0104, the root mean square error decreased by 0.0115 and the mean square error reduction was 7.4%, after the variables of forest layer, forest density, and competition being incorporated into the basic model. The developed quantile regression model performed better than that of the ordinary least square method in simulating the maximum crown width of a single tree in the forest stand. The selected best quantile of the quantile regression model for the upper forest layer and lower forest layer was 0.96 and 0.93, respectively. The linear quantile regression model with the mixed effect was superior to the traditional quantile regression model in Akaike, Bayesion and HQ information criterion and other evaluation para-meters, the standard error for the parameters of estimates was significantly reduced, and the introduced mixed effect well explained differences among different plots. For the upper forest layer and lower forest layer, the maximum crown width decreased with increasing stand density, increased with increasing relative diameters. The influence of stand density on the crown width of the lower forest layer was greater than that of the upper forest layer. The crown width would increase first and then decrease with the increases of DBH when the stand density was large enough. The mixed effect of the quantile regression model developed here could significantly improve the fitting stability of the model. The sustainable development of Korean pine plantation in the mountainous area of eastern Liaoning Pro-vince should be realized by adjusting stand density and moderate tending and thinning in the future.


Subject(s)
Forests , Pinus , China , Linear Models , Republic of Korea , Trees
7.
Front Immunol ; 13: 920253, 2022.
Article in English | MEDLINE | ID: mdl-35911687

ABSTRACT

Background: Patients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear. Methods: A total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively. Results: To the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (>10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1-mutant patients. Conclusions: Genomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.


Subject(s)
Laryngeal Neoplasms , Receptor, Notch1 , Cyclin-Dependent Kinase Inhibitor p16 , Humans , Immunity/genetics , Laryngeal Neoplasms/complications , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/surgery , Mutation , Neoplasm Recurrence, Local/pathology , Receptor, Notch1/genetics , Receptor, Notch1/immunology
8.
Anticancer Drugs ; 33(10): 1186-1190, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35946569

ABSTRACT

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved response in all stages of patients with EGFR positive mutations in nonsmall cell lung cancer. However, the primary resistance mechanism of EGFR-TKIs has not been thoroughly revealed. Here, we described a case of a 64-year-old male with lung adenocarcinoma presented primary resistance on osimertinib combined with bevacizumab and platinum-based chemotherapy, next-generation sequencing revealed EGFR exon 21 L858R mutation and MET gene amplification. Afterward, savolitinib monotherapy was started until now, and the treatment was temporarily successful, the last follow-up clinical evaluation was near complete response, the progression-free survival has over 7 months. Our case highlights that EGFR-TKIs may be not the optimal choice for lung adenocarcinoma with primary EGFR -sensitive mutation with MET amplification simultaneously, whereas MET inhibitor alone may be an effective treatment option. In clinical practice, we should fully consider the possibility of primary resistance in EGFR-TKIs administration.


Subject(s)
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Acrylamides , Adenocarcinoma of Lung/drug therapy , Aniline Compounds/therapeutic use , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Humans , Indoles , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Protein Kinase Inhibitors/pharmacology , Pyrazines , Pyrimidines , Triazines
10.
Front Oncol ; 12: 853211, 2022.
Article in English | MEDLINE | ID: mdl-35359396

ABSTRACT

Niraparib, an oral, potent, highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, has promising clinical benefit for maintenance treatment of patients with ovarian cancer in partial response to platinum-based chemotherapy, especially in patients with BRCA mutation. In publicly available niraparib treatment-related adverse events, gastrointestinal disorders and hematological toxicities were most commonly reported with manageable safety profile. Herein, we first describe a severe and never-reported pulmonary embolism (PE) associated with the use of niraparib in a patient with BRCA mutation advanced high-grade serous ovarian cancer and received anticoagulant therapy after PE. There have been no reports of PE caused by the use of niraparib in patients with advanced high-grade serous ovarian cancer; knowledge of the occurrence of PE after the use of niraparib may assist other clinicians in managing this rare but potentially serious toxic effect.

11.
Front Oncol ; 12: 837219, 2022.
Article in English | MEDLINE | ID: mdl-35299735

ABSTRACT

Novel adjuvant strategies are needed to optimize outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). The adjuvant treatment of ROS Proto-Oncogene 1 (ROS1) fusion-positive resected NSCLC is challenging because there is no curative confirmed randomized controlled trial. Next-generation sequencing (NGS) and immunohistochemistry (IHC) staining were performed on the biopsy sample. In this case, we identified a novel LDLR-ROS1 fusion in a resectable stage IIIA NSCLC patient. The patient received crizotinib as adjuvant treatment and achieved recurrence-free survival (RFS) for 29 months, without significant symptoms of toxicity. In this case, we report a novel LDLR-ROS1 fusion responding to crizotinib in a patient with lung adenocarcinoma, supporting the use of adjuvant treatment with the ROS1 inhibitor exerting clinical survival benefit in ROS1 fusion-positive resected NSCLC.

13.
Oral Oncol ; 121: 105436, 2021 10.
Article in English | MEDLINE | ID: mdl-34371452

ABSTRACT

BACKGROUND: Sarcomatoid carcinoma (SC) of the head and neck (HN) is a rare disease that has both sarcomatoid and cancerous components. The genetic background and mechanisms of tumorigenesis remain largely unrevealed, and the progress of precision therapy has been limited. METHODS: Targeted DNA-based next-generation sequencing (NGS) was performed by a 539 genes panel of pan-cancer in 12 patients with SC of the HN to identify their genetic alterations and investigate clinically actionable mutations for use in precision treatment. RESULTS: TP53 was identified as the most frequently mutated gene. Genes related to the cell cycling, chromatin remodeling and histone modification were found to be frequently mutated in patients with SC of the HN. Alterations in receptor tyrosine kinases (RTKs) were also found in six patients. In addition, four patients had mutations in members of the downstream RAS and PI3-kinase pathways, PIK3CA was identified as the most frequently mutated gene in this pathway. The tumor mutation burden (TMB) value ranged from 0.71 to 14.71 per megabase, with a median of 4.34. The TMB value of PIK3CA mutation patients was significantly higher than that of PIK3CA wild-type patients. CONCLUSIONS: This was the first study to investigate genomic alterations specifically in Chinese patients with SC of the HN. Our research results showed that 10 out of 12 patients can match the targeted therapies or immunotherapy currently available in clinical practice or active clinical trials, suggesting precision therapy has the potential utility to improve the long-term prognosis for patients with the rare disease. Due to the small number of patients in this study, the findings need to be validated in a larger cohort.


Subject(s)
Carcinoma , Head and Neck Neoplasms/genetics , Biomarkers, Tumor , Carcinoma/genetics , China , Class I Phosphatidylinositol 3-Kinases/genetics , DNA Mutational Analysis , Genomics , Humans , Mutation , Rare Diseases
14.
Invest New Drugs ; 39(5): 1436-1438, 2021 10.
Article in English | MEDLINE | ID: mdl-33913072

ABSTRACT

Gastric cancer (GC) has the third highest rate of cancer incidence and mortality worldwide. First-line immune checkpoint inhibitor (ICI) therapy for advanced GC led to landmark breakthroughs, but which GC patients are most likely to benefit from ICI therapy needs to be investigated in depth and identified via valuable biomarkers. In this letter, we describe superior outcomes in Asian patients than in North American and European patients treated with ICI therapy, and we speculate that positive H. pylori status may be a beneficial prognostic factor for ICI therapy in patients with GC. Many studies have revealed that H. pylori-activated immune responses improve prognosis in patients with GC via increased PD-L1 expression and CD3+ T cells. We propose that H. pylori status should be emphasized in ongoing or forthcoming ICI therapy trials to maximize the benefits of treatment for patients with advanced GC. Further research is required to better understand the mechanisms of inflammation and cancer progression.


Subject(s)
Helicobacter Infections/epidemiology , Immune Checkpoint Inhibitors/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/ethnology , CD3 Complex/metabolism , Hedgehog Proteins/metabolism , Helicobacter pylori , Humans , Racial Groups , Stomach Neoplasms/pathology
15.
Invest New Drugs ; 39(5): 1419-1421, 2021 10.
Article in English | MEDLINE | ID: mdl-33835358

ABSTRACT

Compound epidermal growth factor receptor (EGFR) mutations are defined as double or multiple independent mutations of the EGFR tyrosine kinase domain (TKD), in which an EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutation is identified together with a mutation of unclarified clinical significance. Lung adenocarcinoma with compound EGFR mutation shows poor clinical response to EGFR-TKIs. Kobayashi et al. reported a non-small-cell lung cancer (NSCLC) patient whose tumor had EGFR exon21 L858R/A871G mutation presented rapid disease progression to erlotinib. However, in this case, we present an EGFR exon21 L858R/A871G mutation patient exerted significant benefit to icotinib, another first-generation EGFR-TKI, indicating that different EGFR-TKIs have diversiform sensitive sites and therapeutic effects, consistent mutation sites might achieve heterogeneous benefits from different EGFR-TKIs. Our case report provides promising EGFR-TKI for clinical treatment with EGFR exon21 L858R/A871G mutation in NSCLC. More dedicated efforts are needed to clarify their biologic effects on disease course and drug responsiveness.


Subject(s)
Adenocarcinoma of Lung/drug therapy , Antineoplastic Agents/therapeutic use , Lung Neoplasms/drug therapy , Protein-Tyrosine Kinases/antagonists & inhibitors , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Crown Ethers , ErbB Receptors/genetics , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Quinazolines
18.
Pain Physician ; 21(5): E555-E564, 2018 09.
Article in English | MEDLINE | ID: mdl-30282403

ABSTRACT

BACKGROUND: Over-expression of spinal protein kinase Cγ(PKCγ) contributes to the induction of persistent bilateral hyperalgesia following inflammatory injury, yet the role of spinal PKCγ in short- and long-lasting pain behavior is poorly understood. OBJECTIVE: This study aimed to characterize the contribution of spinal PKCγ to spontaneous pain and long-lasting bilateral hyperalgesia in formalin-induced inflamed mice using pharmacological inhibition. STUDY DESIGN: Laboratory animal study. SETTING: The study was performed in the Department of Human Anatomy and K.K. Leung Brain Research Centre, Preclinical School of Medicine, the Fourth Military Medical University (Xi'an, China) and the Department of Anesthesiology, Fuzhou General Hospital (Fuzhou, China). METHODS: Male mice were unilaterally intraplantarly injected with formalin to induce inflammatory pain. Spontaneous pain behaviors, including flinches and lickings, were recorded by off-line video during the first hour post-injection and counted. Using von Frey tests, long-lasting bilateral mechanical paw withdrawal thresholds were determined before injection and at indicated time points thereafter. Temporal expression of spinal PKCγ was observed by immunohistochemical staining. For pharmacological inhibition, mice were treated daily with intrathecal Tat carrier or selective PKCγ inhibitor KIG31-1, from 1 hour prior to 10 days after formalin injection. Spontaneous pain behaviors and long-lasting bilateral mechanical hyperalgesia were assessed. Spinal PKCγ expression was also observed by using immunohistochemical staining and western blot. RESULTS: The number of PKCγ-immunoreactive (ir) spinal neurons was significantly higher at 10 days, but not 2 hours, after formalin intraplantar injection, and accompanied by long-lasting bilateral hyperalgesia. Furthermore, long-lasting bilateral hyperalgesia could be reversed by pharmacological inhibition of over-expressed spinal PKCγ; however, pretreating with intrathecal KIG31-1 showed no antinociceptive effects on short-term spontaneous pain behaviors. LIMITATIONS: All results were obtained from the mice and no PKCγ inhibitors were available through clinical practice. Therefore, it remains difficult to draw definitive connections between animal research and human application. CONCLUSION: Our findings suggest that spinal PKCγ plays a predominant role in long-lasting bilateral hyperalgesia, but not in the spontaneous pain behaviors induced by formalin. KEY WORDS: Formalin, spontaneous pain, mechanical hyperalgesia, protein kinase C gamma, KIG31-1, mice.


Subject(s)
Chronic Pain/enzymology , Hyperalgesia/enzymology , Protein Kinase C/metabolism , Spinal Cord/enzymology , Animals , Behavior, Animal/drug effects , China , Chronic Pain/chemically induced , Formaldehyde/toxicity , Hyperalgesia/chemically induced , Male , Mice , Pain Measurement/methods , Rats, Sprague-Dawley , Spinal Cord/drug effects
19.
Huan Jing Ke Xue ; 38(10): 4084-4091, 2017 Oct 08.
Article in Chinese | MEDLINE | ID: mdl-29965191

ABSTRACT

A C2-C6 hydrocarbons monitoring campaign was carried out in the Beijing Southeastern Urban Area during December 2015. Twenty-five compounds excluding benzene were detected by an on-line VOCs analyzer; the sum of their concentrations is referred to as C2-C6 HCs in this study. During the monitoring period, C2-C6 HCs ranged from 12.4×10-9 to 297.5×10-9. The mean value of C2-C6 HCs reached 29.4×10-9, 63.2×10-9, 85.5×10-9, 94.9×10-9, and 131.8×10-9, respectively, in AQ Ⅰ (air quality) (hourly PM2.5<35 µg·m-3), AQ Ⅱ (hourly PM2.5:35-75 µg·m-3), AQ Ⅲ (hourly PM2.5:75-150 µg·m-3), AQ Ⅳ (hourly PM2.5:150-250 µg·m-3), and AQ Ⅴ (hourly PM2.5:>250 µg·m-3). Moreover, the mole percentage of alkanes, alkenes, and ethyne significantly varied, 47% vs. 59%, 45% vs. 30%, and 7% vs. 12% (AQ I vs. AQ V). The diurnal variation of C2-C6 HCs presented two peaks at 08:00-09:00 and 17:00-18:00 not only in clean days (when 24-h PM2.5<75 µg·m-3) but also in polluted days (when 24-h PM2.5>75 µg·m-3). This result is consistent with the normal traffic pattern and indicates the significant impact of vehicle emissions on atmospheric hydrocarbon concentrations. Furthermore, we calculated the HCs/CO (×10-9/×10-6) ratio to prevent the impact of meteorological diffusion on C2-C6 HCs and to trace the physical transport process and the chemical degradation process of hydrocarbons. The C2-C6 HCs/CO ratio and the individual hydrocarbon to CO ratio presented a notable decreasing trend with worsening air quality, 90.6 (AQ Ⅰ), 63.8 (AQ Ⅱ), 56.9 (AQ Ⅲ), 37.4 (AQ Ⅳ), and 36.4 (AQ Ⅴ). However, the rate of decrease in the ratio of individual hydrocarbons to CO in the polluted period (AQ Ⅲ-Ⅴ) relative to the clean period (AQ I-Ⅱ) was never effectively related to the kinetic parameters of the reactions with the OH radical. Therefore, the strong chemical degradation of C2-C6 hydrocarbons in the polluted air was denied as the main reason. The HYSPLIT trajectory model showed that the transported air mass from the north and northwest and from the south and southwest prevail in the clean period and in the polluted period, respectively. Compared to the northern region, there were more sources of fossil fuel combustion in the southern region, which led to a lower HCs/CO ratio for the air mass in the southern region. Therefore, the increase in C2-C6 hydrocarbons during the polluted period was not only caused by the accumulation of local emissions but also by the air mass transport from the south.

20.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(12): 1609-1615, 2016 Dec 20.
Article in Chinese | MEDLINE | ID: mdl-27998853

ABSTRACT

OBJECTIVE: To evaluate the sensitivity and specificity of CD8+CD28+/CD8+CD28- T lymphocyte balance in predicting the gastrointestinal hemorrhage (GH) in patients with inflammatory bowel disease (IBD). METHODS: Forty-nine IBD patients, including 30 with ulcerous colitis (UC) and 19 with Crohn's disease (CD), were enrolled to test peripheral blood CD8+CD28+ and CD8+CD28- T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic (ROC) curves were used to test the efficiency of CD8+CD28+/CD8+CD28- T lymphocyte balance to predict GH. The differences in lasting time of remission (LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8+ T lymphocytes and the factors were analyzed. RESULTS: The utilization rates of immunosuppressant, steroids, and biological agent (BA) were significantly higher in CD patients than in UC patients (P=0.003, 0.043 and 0.002, respectively). The frequencies of CD8+CD28+T cells were obviously higher in UC patients than those in CD patients (t=3.022, P=0.004). CD8+CD28+T cells, CD8+CD28- T cells, and especially CD8+CD28+/CD8+CD28- ratio (area under curve of 0.977, P=0.000; cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH (P<0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer (Χ2=9.730, P=0.002; Χ2=15.981, P=0.000). CD8+CD28+/CD8+CD28- ratio was significantly related to both BA (P=0.009) and surgery (P=0.038). CONCLUSION: Both decreased CD8+CD28+T cells and elevated CD8+CD28-T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.


Subject(s)
CD28 Antigens , CD8 Antigens , CD8-Positive T-Lymphocytes , Gastrointestinal Hemorrhage/immunology , Inflammatory Bowel Diseases/immunology , Colitis, Ulcerative/immunology , Crohn Disease/immunology , Flow Cytometry , Humans , ROC Curve , Sensitivity and Specificity
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