To explore the antagonistic effect of gingerols against the inflammation induced by lectin from Pinellia ternata. In this study, ELISA method was used to determine the effect of different extracts from gingerols on the release of inflammatory factor TNF-α from macrophages induced by lectin from P. ternata. The fluorescence probe was used to determine the effect of gingerols on the changes in ROS of macrophages induced by lectin from P. ternata. The western-blot method was applied to study the effect of gingerols on the increase in expression of cell receptor interacting protein RIP3 in macrophages induced by lectin from P. ternata. The scanning electron microscope (SEM) was used to study the effect of gingerols on morphological changes in macrophages induced by lectin from P. ternata. According to the results, gingerols can significantly inhibit the release of inflammatory factor from macrophages induced by lectin from P. ternata, ROS overproduction and increase in RIP3 expression. SEM results showed that gingerols can inhibit the cytomorphosis and necrocytosis induced by lectin from P. ternata. Fresh ginger's detoxication may be related to gingerols' effects in inhibiing release of inflammatory factor, ROS overproduction and increase in RIP3 expression caused by macrophages induced by lectin from P. ternata, which are mainly inflammatory development.
Animals ; Catechols ; pharmacology ; Cells, Cultured ; Drug Antagonism ; Fatty Alcohols ; pharmacology ; Ginger ; chemistry ; Lectins ; toxicity ; Macrophages ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Pinellia ; chemistry ; toxicity ; Reactive Oxygen Species ; metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo investigate the application effect of damage control orthopedics for the treatment of severe multiple fractures.

METHODSFrom January 2014 to December 2016, 23 patients with severe multiple fractures were treated with the damage control orthopedics (DCO), included 14 males and 9 females with an average age of (41.57±8.29) years old ranging from 28 to 60 years old; the NISS averaged(27.70±5.44) points ranging from 18 to 40 points. As the control group, 27 patients with severe multiple fractures were treated by the early total care(ETC) technology from Jan. 2007 to Dec. 2019, included 16 males and 11 females with an average age of (38.33±9.99) years old ranging from 19 to 55 years old, the NISS averaged (31.07±6.46) points ranging from 20 to 43 points. The ICU recovery time, blood transfusion, total operation time, mortality, complication and length of hospital stay were observed and compared between two groups.

RESULTSIn the DCO group, there were 22 cases surviving and 1 case death, 3 cases of postoperative complication contained 2 cases of adult respiratory distress syndrome, 1 case pin of infection in external fixation. In ETC group, there were 25 cases surviving and 2 cases death, 10 cases of postoperative complication contained 4 cases of adult respiratory distress syndrome and 3 cases of pin infection in external fixation, 1 case of wound infection and 2 cases of multiple organ failure. There was statistically significant difference between two groups in blood transfusion in operation, the ICU recovery time, and complications(<0.05). There was no statistically significant difference in total operation time, length of hospital stay and mortality between two groups(>0.05).

CONCLUSIONSFor patients with severe multiple fractures, application of damage control orthopedics can significantly reduce the postoperative complications, ICU recovery time and intraoperative blood transfusion, provide a certain basis for clinical treatment of such patients.

OBJECTIVETo assess the experimental and clinical data regarding the effects of electromagnetic fields (EMFs) on fracture non-union.

DATA SOURCESThe English language literature regarding EMFs on fracture non-union were searched using MEDLINE, Web of Science and Embase, for the period January 2006 to June 2011. The search terms were electromagnetic fields and non-union/bone marrow stem cells (BMSCs)/bone.

STUDY SELECTIONArticles were included in the review if they were related to the use of EMFs on BMSCs or bone tissue. Papers without full manuscripts available were excluded.

RESULTSThe basic and clinical research in this field, while somewhat limited, supports the insightful application of EMFs to ameliorate disability due to fracture non-union.

CONCLUSIONSFurther basic and clinical research to validate the use of EMFs in facilitating function and bone reparative processes in fracture non-union is required.

Animals ; Bone Regeneration ; physiology ; Electromagnetic Fields ; Humans

OBJECTIVETo study the toxic mechanism of toxic raphides from Pinellia ternata.

METHODMouse peritoneal macrophage in vitro culture model was adopted to study dose-dependent and time-dependent curves of toxic raphides, with TNF-alpha, IL-1beta and IL-6 in supernatant as indexes. Scanning electron microscopy was used to observe the changes in surface morphology of raphides-treated macrophages. Macrophages-neutrophils co-cultured the transport model to study the effect of toxic raphides' stimulation of macrophages on neutrophils migration.

RESULTToxic raphides' stimulation of macrophages could cause the increase in the levels of TNF-alpha, IL-1beta and IL-6 released, and showed dose dependence and time dependence. Scanning electron microscopy showed that toxic raphides were swallowed by macrophages, with notable cell membrane creases, increase in the number of pseudopods and decrease in integrity of cell membranes, and could significantly induce migration of neutrophils.

CONCLUSIONThe inflammatory process induced by toxic raphides is mainly mediated by macrophages. The toxic mechanism of toxic raphides from P. ternata is that toxic raphides penetrate into tissues to activate resident macrophages, release phagocytic and inflammatory cytokines, and cause migration of neutrophils, which finally results in acute inflammatory response.

Animals ; Drugs, Chinese Herbal ; toxicity ; Inflammation Mediators ; toxicity ; Interleukin-1beta ; immunology ; Interleukin-6 ; immunology ; Macrophages, Peritoneal ; drug effects ; immunology ; Male ; Mice ; Mice, Inbred ICR ; Pinellia ; chemistry ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVETo extract and separate toxic components from Phytolaccae Radix, and to comare the changes in toxicity of Phytolaccae Radix before and after being processed with vinegar.

METHODThe mucous membrane irritation response, mouse peritoneal inflammation model and in vitro macrophages release NO model were applied to compared the changes in inflammatory toxicity of toxic components from Phytolaccae Radix before and after being processed with vinegar.

RESULTToxic components of Phytolacca Radix had significant inflammatory toxicity, which could cause conjunctival edema in rabbits, and increase of PGE2 and macrophages release NO content in peritoneal exudate in mice. After being processed with vinegar, they showed reduced irritation, which resulted in decrease of PGE2 and macrophages release NO content in peritoneal exudate in mice.

CONCLUSIONAfter being processed with vinegar, the toxicity of toxic components from Phytolacca Radix decreased obviously.

Acetic Acid ; chemistry ; Animals ; Chemistry, Pharmaceutical ; methods ; Drugs, Chinese Herbal ; isolation & purification ; toxicity ; Eye ; drug effects ; immunology ; Male ; Mice ; Mice, Inbred ICR ; Phytolacca ; chemistry ; Rabbits

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

BACKGROUNDRepair of large bone defects remains a challenge for clinicians. The present study investigated the ability of mesenchymal stem cells (MSCs) and/or periosteum-loaded poly (lactic-co-glycolic acid) (PLGA) to promote new bone formation within rabbit ulnar segmental bone defects.

METHODSRabbit bone marrow-derived MSCs (passage 3) were seeded onto porous PLGA scaffolds. Forty segmental bone defects, each 15 mm in length, were created in the rabbit ulna, from which periosteum was obtained. Bone defects were treated with either PLGA alone (group A), PLGA + MSCs (group B), periosteum-wrapped PLGA (group C) or periosteum-wrapped PLGA/MSCs (group D). At 6 and 12 weeks post-surgery, samples were detected by gross observation, radiological examination (X-ray and micro-CT) and histological analyses.

RESULTSGroup D, comprising both periosteum and MSCs, showed better bone quality, higher X-ray scores and a greater amount of bone volume compared with the other three groups at each time point (P < 0.05). No significant differences in radiological scores and amount of bone volume were found between groups B and C (P > 0.05), both of which were significantly higher than group A (P < 0.05).

CONCLUSIONSImplanted MSCs combined with periosteum have a synergistic effect on segmental bone regeneration and that periosteum plays a critical role in the process. Fabrication of angiogenic and osteogenic cellular constructs or tissue-engineered periosteum will have broad applications in bone tissue engineering.

Animals ; Bone Regeneration ; physiology ; Cells, Cultured ; Lactic Acid ; chemistry ; Mesenchymal Stromal Cells ; cytology ; Periosteum ; cytology ; Polyglycolic Acid ; chemistry ; Rabbits ; Tissue Engineering ; methods ; Tissue Scaffolds ; chemistry

Objective:To explore the risk factors of renal function progression in patients with acute renal injury (AKI) after moderate hypothermic circulatory arrest surgery in acute aortic dissection (AD).Methods:Retrospective analysis was made base on the data of 290 patients with acute AD who underwent surgical treatment from January 2014 to August 2022 in the Affiliated Hospital of Jining Medical University. According to the Kidney Disease: Improving Global Outcomes (KDIGO) AKI diagnostic criteria in 2015, patients with AKI after surgery were selected as the study objects. Patients with progressive deterioration of renal function or required continuous renal replacement therapy after AD operation were defined as the progression group of AKI, the other patients with gradual improvement of renal function after AD operation were defined as the improvement group of AKI. The clinical data of the two groups were compared, and the risk factors for the progression of AKI after AD were analyzed by multivariate logistic regression.Results:A total of 290 AD surgeries were completed, of which 143 cases developed AKI after surgery, including 81 cases in AKI progression group and 62 cases in AKI improvement group. In the progression group of AKI, before surgery the proportion of patients with coronary heart disease: 24.7% (20/81) vs.11.3% (7/62), serum creatinine (Scr) >133 μmol/L: 24.7% (20/81) vs. 3.2% (2/62), pericardial tamponade: 22.2% (18/81) vs. 8.1% (5/62), lower limb ischemia: 25.9% (21/81) vs. 3.2% (2/62) were significantly increased. Postoperative acute physiology and chronic health evaluation Ⅱ (APACHE) score: 14.00 (9.00, 19.75) scores vs. 10.00 (7.00, 12.00) scores, ICU hospitalization days: 8 (5, 13) d vs. 5 (3, 7) d, postoperative mortality: 24.7%(20/81) vs. 1.6%(1/62), the proportion of KDIGO phase 3 ratio: 46.9%(38/81) vs. 3.2%(2/62), postoperative infection: 61.7%(50/81) vs. 38.7% (24/62), low cardiac output syndrome: 29.6% (24/81) vs. 6.5% (4/62), cerebral infarction complications: 38.2%(31/81) vs. 16.1%(10/62), and mortality after surgery were also higher. Compared with improvement group of AKI, all differences were statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that preoperative lower limb ischemia ( OR = 9.430, 95% CI 1.975 to 45.032, P = 0.005), postoperative low cardiac output syndrome ( OR = 5.288, 95% CI 1.543 to 18.126, P = 0.008), and postoperative infection ( OR = 2.273, 95% CI 1.022 to 5.057, P = 0.044) were independent risk factors for the progression of AKI after AD surgery. Conclusions:The independent risk factors of renal function progression in patients with AKI after hypothermic circulatory arrest surgery in acute AD include preoperative lower limb ischemia, postoperative low cardiac output syndrome, and postoperative infection.

OBJECTIVETo investigate the correlation of single nucleotide polymorphisms (SNP) of XRCC1 gene to hereditary susceptibility of colorectal cancer.

METHODSXRCC1 genotypes in 124 colorectal cancer patients and 214 matched healthy people as control were analyzed by SnaP Shot SNP-typing technique. Five different inheritance models including codominant, dominant, recessive, overdominant and log-additive were analyzed using logistic regression model. The haplotype distribution was estimated with phase and its correlation with the risk of colorectal cancer was evaluated.

RESULTSThe frequencies of mutant 25487G-A, 25489C-T and 1799782C-T alleles were 0.20, 0.11, 0.32 respectively in the patients, and 0.23, 0.13, 0.34 in the controls. There was no significant correlation of polymophisms of XRCC1 gene to the risk of colorectal cancer in 5 different inheritance models (P>0.05). GCT, GCC, ACC and GTC were the most common haplotypes and the odds ratios were 1, 1.35, 0.90 and 0.84 respectively. There was no significant difference of distribution between 2 groups in haplotypes.

CONCLUSIONPolymorphisms of XRCC1 gene, including rs25487, rs25489, rs1799782, are not associated with to the risk of colorectal cancer.

Colorectal Neoplasms ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Models, Genetic ; Polymorphism, Single Nucleotide ; X-ray Repair Cross Complementing Protein 1

BACKGROUNDMicroRNAs (miRNAs) are small noncoding regulatory RNAs whose aberrant expression may be observed in many malignancies. However, few data are yet available on human primary medulloblastomas. This work aimed to identify that whether miRNAs would be aberrantly expressed in tumor tissues compared with non-tumorous cerebellum tissues from same patients, and to explore a possible role during carcinogenesis.

METHODSA high throughput microRNA microarray was performed in human primary medulloblastoma specimens to investigate differentially expressed miRNAs, and some miRNAs were validated using real-time quantitative RT-PCR method. In addition, the predicted target genes for the most significantly down- or up-regulated miRNAs were analyzed by using a newly modified ensemble algorithm.

RESULTSNine miRNA species were differentially expressed in medulloblastoma specimens versus normal non-tumorous cerebellum tissues. Of these, 4 were over expressed and 5 were under expressed. The changes ranged from 0.02-fold to 6.61-fold. These findings were confirmed using real-time quantitative RT-PCR for most significant deregulated miRNAs (miR-17, miR-100, miR-106b, and miR-218) which are novel and have not been previously published. Interestingly, most of the predicted target genes for these miRNAs were involved in medulloblastoma carcinogenesis.

CONCLUSIONSMiRNAs are differentially expressed between human medulloblastoma and non-tumorous cerebellum tissue. MiRNAs may play a role in the tumorigenesis of medulloblastoma and maybe serve as potential targets for novel therapeutic strategies in future.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Medulloblastoma ; genetics ; MicroRNAs ; genetics ; metabolism ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction