ABSTRACT
OBJECTIVE@#Programmed cell death 6 (PDCD6), a Ca 2+-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas (HCCs).@*METHODS@#The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium (MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3β/β-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6.@*RESULTS@#The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6 promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3β/β-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis.@*CONCLUSION@#PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3β/β-catenin signaling and might be a potential target for HCC progression.
Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , beta Catenin/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Cell Line , Cell Proliferation , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Calcium-Binding Proteins/metabolism , Apoptosis Regulatory Proteins/geneticsABSTRACT
ObjectiveThe study aims to determine whether the horizontal posterior displacement of the distal clavicle in patients with acromioclavicular joint dislocation can be corrected via the application of modified intraoperative axillary fluoroscopy. MethodsFrom February 2019 to April 2021， 50 patients with Rockwood type Ⅲ acromioclavicular joint dislocation eligible for inclusion were randomly divided into two groups： the normal （32 cases） and the experimental （18 cases）. The conventional anteroposterior position radiographs were obtained to detect the surgery effect on the patients in the normal group. In experimental group， modified intraoperative axillary radiographs were obtained， with the concept of polar coordinates introduced to reduce the horizontal posterior translation of the clavicle. Then we compared the perioperative parameters， such as average operative time， intraoperative blood loss between the two groups. The Constant score was used for assessing the postoperative function of the shoulder joint in the follow-up visits. ResultsNo statistically significant difference was found in gender， age， duration of injury， underlying diseases， intraoperative blood loss and operative time between the two groups. The postoperative shoulder function score of the experimental group was higher than that of the normal group. ConclusionsThe application of modified intraoperative axillary fluoroscopy is recommendable for accurately reducing posterior translation of the distal clavicle， and meanwhile helpful for the precise placement of the clavicular plate.
ABSTRACT
@#BACKGROUND: Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy (SAE) is a major complication. Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions. Our study aimed to explore the potential protective function of rosuvastatin against SAE. METHODS: Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the “Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome” study (SAILS trial, ClinicalTrials.gov number: NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of the SAILS dataset. Baseline characteristics, therapy outcomes, and adverse drug events were compared between groups. RESULTS: A total of 86 patients were eligible for our study. Of these patients, 51 were treated with rosuvastatin. There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group (32.1% vs. 57.1%, P=0.028). However, creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group (233 [22-689] U/L vs. 79 [12-206] U/L, P=0.034). CONCLUSION: Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.
ABSTRACT
In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of 1H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.
ABSTRACT
Esophageal carcinoma is one of the malignant tumors with a high mortality rate， accounting for nearly 570，000 cancer deaths worldwide annually， and this number is increasing year by year. In recent years， despite the continuous improvement of treatment programs for esophageal carcinoma， the overall five-year survival rate of esophageal carcinoma is still less than 20% due to the development of drug resistance and the tolerance of patients during the treatment process. Tumor microenvironment （TME） is composed of various cells and related components with tumor cells as the core and featured by hypoxia， acidosis， chronic inflammation and immunosuppression， which plays an important role in the progression of tumors. Studies have found that tumor-associated fibroblasts， tumor-associated macrophages， myeloid-derived suppressor cells and regulatory T cells in TME can promote the proliferation， migration， invasion， and lymph node metastasis of cancer cells by secreting cytokines and activating pro-inflammatory pathways， and promote cancer progression by inducing the drug resistance of cancer cells and evading immunosuppression. Because cancer-associated cells in TME are genetically more stable than cancer cells， have fewer mutations and have lower chance of drug resistance， targeting cancer-associated cells in TME by regulating TME is a new research direction of cancer therapy. Traditional Chinese medicine has the advantages of multi-component and multi-target. It can participate in the regulation of TME through multiple ways， reduce the number of cancer-associated cells in TME， inhibit crosstalk between TME and cancer cells， and restore immune cell function. It is an important source for the regulation of TME and the research and development of drugs targeting cancer-associated cells in TME. In this paper， the role of cancer-associated cells in the TME of esophageal cancer and the current application of traditional Chinese medicine targeting cancer-associated cells in TME are reviewed， so as to provide reference for the research and development of TME targeted drugs for esophageal carcinoma.
ABSTRACT
In recent years, the focus of anti-cancer agents has gradually shifted from cytotoxic chemotherapy to molecular-targeted agents that interfere with frequently overexpressed or mutated molecules in cancer cells. Compared with cytotoxic chemotherapy, molecular-targeted therapy is a new biological therapy with higher specificity and lower toxicity, however, the adverse reactions caused by molecular-targeted agents cannot be ignored. Diarrhea is one of the most common adverse drug reactions, which could seriously affect the quality of life and even lead to treatment discontinuation and consequently decreased cancer control. To provide a reference for relevant research and clinical medication, we review the current reports on the incidence, pathogenic mechanism, and management of diarrhea induced by the molecular-targeted agents.
ABSTRACT
OBJECTIVE@#To investigate the relationship between the levels of ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH) and interleukin-6 (IL-6) in peripheral serum and cytokine release syndrome (CRS) in patients with relapse and/or refractory multiple myeloma (R/R MM) after receiving chimeric antigen receptor T cells (CAR-T) immunotherapy.@*METHODS@#Twenty-eight patients with R/R MM were treated with 1×10@*RESULTS@#Among the 28 patients, 27 cases (96.4%) developed CRS, 24 cases (85.7%) in 1-2 grade CRS and 3 cases (10.7%) in 3-5 grade. The severity grade of CRS of 27 patients was positively correlated with the peak values of ferritin, CRP, LDH, and IL-6 in peripheral blood (r@*CONCLUSION@#After receiving CAR-T cellular immunotherapy, the incidence of CRS in patients with R/R MM is higher, but most of them are in grade 1 or 2. The severity of CRS is positively correlated with the levels of ferritin, CRP, LDH and IL-6 in peripheral blood.
Subject(s)
Animals , Humans , Mice , Antigens, CD19 , Cytokine Release Syndrome , Immunotherapy, Adoptive , Multiple Myeloma/therapy , Neoplasm Recurrence, Local , Receptors, Chimeric AntigenABSTRACT
To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml
ABSTRACT
OBJECTIVE@#To observe the changes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and nerve function in patients with spinal tuberculosis before and after surgery, explore the timing of surgical intervention, and evaluate its influence on surgical safety.@*METHODS@#A retrospective analysis was conducted on 387 patients with spinal tuberculosis who received surgical treatment from March 2012 to March 2017, including 278 males and 109 females, aged 12 to 86 years old with an average of (49.9±19.1) years. There were 64 cases of cervical tuberculosis, 86 cases of thoracic tuberculosis, 76 cases of thoracolumbar tuberculosis and 161 cases of lumbar tuberculosis. There were 297 patients with single segmental involvementand 90 patients with multiple segmental involvement. Among them, 62 cases presented neurological damage, and preoperative spinal cord neurological function depended on ASIA grade, 5 cases of grade A, 8 cases of grade B, 39 cases of grade C, and 10 cases of grade D. According to the duration of preoperative antituberculosis treatment, the patients were divided into group A (256 cases, receiving conventional quadruple antituberculosis treatment for 2-4 weeks before surgery) and group B (131 cases, receiving conventional quadruple antituberculosis treatment for more than 4 weeks before surgery). The two groups were compared in terms of gender, age, preoperative complicated pulmonary tuberculosis, lesion site, lesion scope, surgical approach, drug resistance and other general clinical characteristics. ESR, CRP, visual analogue scale(VAS), Oswestry Disability Index (ODI), Frankel grade and postoperative complications were observed.@*RESULTS@#All 387 patients were followed up for 12 to 36 (18.3±4.5) months. There were no significant differences in gender, age, preoperative pulmonary tuberculosis, lesion site, lesion range, surgical approach, preoperative drug resistance and other characteristics between two groups. A total of 32 patients in two groups did not heal after surgery, with an incidence rate of 8.27%. The VAS and spinal cord dysfunction index of the two groups were significantly improved after surgery (@*CONCLUSION@#After 2-4 weeks of anti tuberculosis treatment before operation, patients with spinal tuberculosis could be operated upon with ESR and CRP in a descending or stable period. In principle, patients with spinal tuberculosis and paraplegia should be treated as soon as possible after active preoperative management of the complication without emergency surgery.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult , Blood Sedimentation , Retrospective Studies , Spinal Fusion , Thoracic Vertebrae , Tuberculosis, Spinal/surgeryABSTRACT
OBJECTIVE@#To investigate the expression of WTAP gene in acute myeloid leukemia (AML) and its clinical significance.@*METHODS@#74 acute myeloid leukemia patients with non-M3 type and 19 normal donors were selected, and real-time quantitative polymerase chain reaction was used to detect the mRNA expression level of WTAP gene in their bone marrow cells. The relationship between the mRNA expression level of WTAP gene and the clinical characteristics was analyzed.@*RESULTS@#The relative mRNA expression of WTAP gene in the non-M3 AML group was significantly higher than that in the healthy control group, and the difference showed statistically significant (P0.05) according to the classification of FAB. The mRNA expression level of WTAP gene in FLT3-ITD mutated AML patients was higher than that in FLT3-ITD unmutated group (P=0.016), and the mRNA expression level of WTAP gene in AML patients with CEBPα mutation was lower than that in CEBPα unmutated group (P=0.016). The expression level of WTAP mRNA was positively correlated with WT1 expression (r=0.6866, P0.05). The expression level of WTAP mRNA showed no obvious effect on the complete remission of patients after first treatment. The different expression level of WTAP gene at initial diagnosis showed also no effect on the overall survival time of patients.@*CONCLUSION@#The expression level of WTAP gene is increasing in new diagnosed non-M3 acute myeloid leukemia. There is a positive correlation between the expression level of WTAP gene and the expression level of WT1 fusion gene. WTAP mRNA always shows higher expression in patients with FLT3-ITD mutation than that in patients without FLT3-ITD mutation, and shows lower expression in patients with CEBPα mutation than that in unmutated group.
Subject(s)
Humans , Cell Cycle Proteins , Karyotype , Leukemia, Myeloid, Acute/genetics , Mutation , Prognosis , RNA Splicing Factors , Remission Induction , fms-Like Tyrosine Kinase 3/geneticsABSTRACT
Objective To explore the effects of Lycium barbarum soup on retina histological structure and related active substances in mice injured by heroin. Method Totally 120 Kunming mice were randomly divided into control group, heroin group, Lycium barbarum 1 group and Lycium barbarum 2 group. The mice were intraperitoneal
ABSTRACT
Aim To investigate the effects of sinapine thiocyanate (ST) on the malignant biological behavior of cutaneous squamous cell carcinoma A431 and Colo-16 cells, and its mechanism. Methods The fibroblast cells were treated with 20 μmol · L
ABSTRACT
OBJECTIVE@#To compare the clinical effects of three different methods of binding multi-fold rib graft, iliac bone graft and titanium mesh graft in tuberculosis of thoracic vertebra by approach of transverse rib process.@*METHODS@#A hundred and seven patients with tuberculosis of thoracic vertebra received surgical treatment from January 2010 to December 2016 were retrospectively analyzed. The patients were divided into three groups according different methods of bone graft. The surgical approach of the transverse rib process was used in all 107 patients, after thoroughly remove the necrotic tissue of tuberculosis, three different bone grafts were used respectively including iliac bone graft (36 cases, group A), binding multi-fold rib graft (35 cases, group B), titanium mesh bone graft (36 cases, group C). Perioperative indexes, the time required for bone graft during operation, intraoperation blood loss, the loss rate of the anterior edge of the lesion, Cobb angle, postoperative bone graft fusion time, spinal nerve recovery and Oswestry Disability Index were compared among three groups.@*RESULTS@#All the patients were followed up for 13 to 24 months, and the operation time required for bone graft was (23.2±4.1) min in group A, (23.8± 4.4)min in group B, and (25.5±4.2) min in group C, with no statistically significant difference among three groups (@*CONCLUSION@#The approach of transverse rib process for debridement of lesions can effectively treat tuberculosis of thoracic vertebra by binding multi-fold rib graft, iliac bone graft and titanium mesh graft, but binding multi-fold rib graft can effectively avoid iliac bone donor complications, and is an effective alternative to iliac bone graft, which is worth popularizing.
Subject(s)
Humans , Bone Transplantation , Lumbar Vertebrae , Retrospective Studies , Ribs/surgery , Spinal Fusion , Surgical Mesh , Thoracic Vertebrae/surgery , Titanium , Treatment Outcome , Tuberculosis, Spinal/surgeryABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
ABSTRACT
Protein phosphorylation is one of the main ways to activate protein bioactivity and make it participate in cell life activities. Researches have shown that approximately 30% of proteins in the human body are modified by phosphorylation at different levels and at different sites. If the protein phosphorylation modification level or site is abnormal, it will cause the occurrence and development of malignant tumors. Malignant tumors have always been a kind of diseases that endanger human life and health. According to statistics, as many as 18 million malignant tumors and more than 9.6 million deaths occur every year worldwide. With the continuous recognition on the abnormality of protein phosphorylation modification in tumorigenesis and development, the research and development of drugs for abnormality of protein phosphorylation modification has become a focus in the field of tumor therapy at present. Each traditional Chinese medicine(TCM) can be regarded as a natural molecular library, and it participates in the regulation of protein phosphorylation modification level with the advantages of multiple components and multiple targets, with slight side effect and low drug resistance, so TCM is one of the main sources of drug development for regulating protein phosphorylation modification levels. Through the search of multiple databases at home and abroad, it was found that certain monomers, parts extracted from TCM, single-TCM and TCM compounds can affect the tumor progression by regulating the level of protein phosphorylation and exert better anti-tumor effect. Based on the current research status of protein phosphorylation regulation by TCM at home and abroad, we found that TCM can inhibit tumor cell proliferation, invasion and metastasis, angiogenesis, and maintenance of stem cell stemness by regulating protein phosphorylation levels, and exert antitumor effects by promoting apoptosis. In order to clarify the molecular mechanism of TCM in regulating protein phosphorylation level and exerting antitumor effect, and provide evidences for the development and clinical application of antitumor TCM, the authors reviewed the mechanism of TCM in regulating protein phosphorylation level and exerting their antitumor effect from different ways in this paper.
ABSTRACT
Objective:To investigate the topological alterations in brain functional networks following comprehensive treatment including brain-computer interface (BCI) training in subacute stroke subjects. Methods:From January, 2018 to June, 2019, 14 subacute stroke patients with moderate to severe upper limbs paralysis accepted routine physical therapy, occupational therapy and BCI training based on motor imagery, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT) and Wolf Motor Function Test (WMFT) before and after treatment, while the functional connectivity (FC) was investigated with resting state functional magnetic resonance imaging. Results:The scores of FMA-UE, ARAT and WMFT increased after treatment (|t| > 5.298, Z = -3.297, P < 0.01). The FC also increased across the whole brain, including temporal, parietal, occipital lobes and subcortical regions. The FC between left piriform cortex of parietal lobule (BA5L) and right medial surface of temporal lobe (BA48R), as well as those between left precentral gyrus (BA4L) and right anterior transverse temporal gyrus (BA41R) (r > 0.416, P < 0.05). Conclusion:Comprehensive rehabilitation including BCI training may promote recovery of motor function and activities of FC in brain in subacute stroke patients.
ABSTRACT
OBJECTIVE@#To investigate the clinical effect of One-stage posterior debridement combined with lumbar-ilium fixation and bone graft fusion for the treatment of lumbosacral tuberculosis.@*METHODS@#The clinical data of 31 patients with lumbosacral tuberculosis treated by one-stage posterior debridement combined with lumbar-ilium fixation and bone graft fusion from January 2013 to February 2018 were retrospectively analyzed. There were 18 males and 13 females, aged from 18 to 77 years old with an average of (45.9±9.1) years. The lesion segment was form L to S. The preoperative ASIA grading showed that 2 cases were grade B, 17 cases were grade C, 12 were grade D. Pre- and post-operative C reactive protein (CRP), visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), ASIA grade, lumbosacral angle and intervertebral space height were analyzed, the surgery complications, stability of internal fixation, bone fusion were observed.@*RESULTS@#All the 31 patients were followed up for 10 to 24 months with an average of (16.0±3.1) months. One patient with local infection and subcutaneous hydrops was cured by dressing change. Other 30 cases got primary healing without sinus formation and no recurrence of spinal tuberculosis. All the patients were cured, no internal fixation loosening and breakage were found. All bone fusion was successful with an average fusion time of (4.7±1.1) months. At the final follow-up, ESR and CRP were normal, the VAS was decreased from (6.13±1.21) points preoperatively to (1.92±0.57) pioints, the ASIA grading showed that 2 cases were grade C, 6 cases were grade D, and 23 cases were grade E. The lumbosacral angle and intervertebral space height was increased from preoperative (21.42±3.75) °, (7.84±0.41) mm to (27.21±3.12) °, (9.80±0.38) mm at the final follow-up, respectively.@*CONCLUSION@#One-stage posterior debridement combined with lumbar-ilium fixation and bone graft fusion is a practicable, effective and safe method for the treatment of lumbosacral tuberculosis. It can be recommended in clinical application.
ABSTRACT
Objective: To investigate whether and how Fusobacterium nucleatum-related bacterial biofilm modulates the infiltration of tumor-associated macrophages into tumor microenvironment and the response to chemotherapy in colon cancer patients. Methods: Both biofilm-based F.n-culture medium (BF-CM) and planktonic F.n-culture medium, (P-CM) Fusobacterium nucleatum was cultured, and the culture-medium was collected to coculture with CRC cell lines and macrophages. Quantified real time PCR( qRT-PCR) was used to measure genes related to chemoresistance, CCK8 assay was conducted to measure proliferation inhibition rate of chemicals to cancer cells, qRT-PCR was used to measure the expression of genes related to macrophage polarization. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were conducted to evaluate existence of bacterial biofilm and infiltration of macrophages in tumor tissues of colon cancer. Results: Expression of chemoresistance-related genes(e.g. MDR1/Abcb1a/ Abcb1b) were higher in BF-CM treated CRC cells than those in P-CM treated cells. CRC cell inhibition level via LOHP/5-FU were reduced with F.n culture medium(metabolites) co-culture, and much lower in BF-CM group. Expression of M2-polarization markers were also higher after BF-CM treated macrophages than P-CM. Biofilm positivity was higher in recurrent(confirmed by PET-CT, CT, or colonoscopy) colon cancer patients with post-resection adjuvant chemotherapy, than that in non-recurrent ones; correlated with infiltration rate of M2 macrophages. Conclusion: Fusobacterium nucleatumrelated bacterial biofilm can induce M2-polarization of intratumor macrophages and could promote chemoresistance to chemicals in CRC cells, which may contribute to prognosis of colon cancer patients.
ABSTRACT
BACKGROUND@#Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients.@*METHODS@#We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identified for meta-analysis. Main outcomesincluded cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR).@*RESULTS@#Sixteen RCTs involving 1,334 patients were identified. Compared with the atropine-or penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07–1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01–1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06–0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04–1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also significantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS.@*CONCLUSION@#Atropine combined with penehyclidine benefits OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.
ABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.