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Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma, which indicates a high potential of malignancy. The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life; however, it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management. As a major problem in the field of head and neck pathologies, it is imperative to identify biomarkers of malignant transformation in oral leukoplakia. In this review, we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside. Although no single biomarker has yet been applied in the clinical setting, profiling for genomic instability might be a promising adjunct.
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Objective To investigate the mechanism of action of Huzhang Qingmai decoction (HZQMY) on the improvement of cognitive function in mice with chronic cerebral ischemia from the perspective of intestinal flora. Methods A mouse model of chronic cerebral ischemia was established by placing microcoils around the bilateral common carotid arteries to induce bilateral carotid artery stenosis (BCAS). After 12 weeks of intragastric administration, the cognitive function of the mice was measured by the Morris water maze; the myelin damage was analyzed by LFB staining; The contents of the cecum of the mice in each group were extracted and analyzed by 16S rRNA sequencing. Results The results of the water maze experiment showed that the mice in the HZQMY group had a significantly shorter escape latency, increased the number of crossings platform and the percentage of target quadrants. LFB staining showed that the white matter damage in the model group was severe; the white matter damage in the HZQMY group was milder. The results of 16S rRNA sequencing showed that compared with the model group, the abundance of Verrucomicrobiota, Akkermansia, and ErysiPelatoclostridium capsulatum in the intestinal flora in HZQMY group was significantly reduced (P<0.05), while the abundances of Eubacterium_xylanoPhilum and Allobaculum were significantly increased (P<0.05). Conclusion The protective effect of HZQMY, which has the effect of improving cognitive function in mice with chronic cerebral ischemia, may be related to the regulation of intestinal flora in mice with chronic cerebral ischemia.
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Objective To explore the mechanism of motherwort in the treatment of nerve injury. Methods The active components of motherwort were obtained by searching TCMSP and BATMAN-TCM databases. The action targets of candidate compounds were collected and predicted from TCMSP and SwissTargetPrediction (STP) databases. The target genes corresponding to the active components of motherwort were obtained by using the standardized database of disease targets (Uniprot). The potential targets of motherwort in the treatment of nerve injury were obtained by mapping the disease genes of nerve injury with the three databases of Genecards, DisGenet and OMIM. The network topology analysis software Cytoscape 3.6.0 was used to construct the action target network of motherwort active components. The protein interaction platform database (STRING) was used to construct the interaction relationship between action targets. The target protein interaction (PPI) network was constructed by introducing Cytoscape 3.6.0 software. Through STRING database, GO enrichment analysis and KEGG pathway enrichment analysis were carried out to analyze the target points of motherwort in the treatment of nerve injury. Results 19 active components were screened from motherwort, involving 654 action targets, including 426 action targets related to nerve injury and 6 key targets. These target genes were mainly involved in biological regulation, oxidative stress response and cell communication and other biological processes. Molecular functions were mainly related to protein binding, ion binding and catalytic reduction. They were enriched outside the cell membrane. Its mechanism was related to signal pathways such as MAPK, Toll-like receptor, PI3K-Akt, TNF, IL-17, and apoptosis. Conclusion The active components of motherwort may play a protective role on nerve injury through anti-inflammation, anti-apoptosis and promoting cell growth.
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Innate immunity is the host's first line defense against pathogens invading to the body. Detection of abnormal nucleic acids in the cytoplasm showed that some conserved pathogen associated molecular patterns (PAMPS) triggered type I interferon (IFN) -mediated innate immune responses. The DNA sensor— cGAS (cGAMP Synthase) recognizes and binds to host or pathogen cytoplasmic DNA, promotes the formation of the second messenger cGAMP (cyclic GMP-AMP), and triggers STING (stimulator of interferon genes) dependent downstream signaling. Here we briefly describe the latest progress of the cGAS-cGAMP-STING pathway and its important role in antivirus, and provide new ideas for virus prevention research and new direction for the development of antiviral drugs.
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Ossifying fibroma (OF) and fibrous dysplasia (FD) are two fibro-osseous lesions with overlapping clinicopathological features, making diagnosis challenging. In this study, we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations (CNAs) using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples. Freshly frozen tissue specimens from OF (n = 29) and FD (n = 28) patients were obtained for analysis. Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection (LCM), with ~30-50 cells (5 000-10 000 µm
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Humans , DNA Copy Number Variations , Diagnosis, Differential , Fibroma, Ossifying/genetics , Fibrous Dysplasia of Bone/genetics , Galactosyltransferases , Jaw , Neoplasm Recurrence, Local , Nuclear Proteinsالملخص
Objective To investigate the effects of upadacitinib on the polarization and inflammation of BV2 microglia after oxygen glucose deprivation/recovery (OGD/R) and to explore its mechanism of action. Methods The experiment was divided into 3 groups: control group, OGD group and upadacitinib treatment group. After BV2 cells were treated with OGD/R, MTT was used to detect cell survival rate. Wound scratch assay was used to detect the cell migration ability. qPCR was used to detect mRNA levels of M1-type polarization markers (CD11b, CD32, iNOS) and M2-type polarization markers (Arg-1, IL-10, CD206) of BV2 cells. ELISA was used to detect the levels of IL-1β, IL-6, and TNF-α in the culture medium. Western blot was used to detect the expression levels of JAK1/STAT6 pathway-related proteins. Results Upadacitinib increased the survival of BV2 cells after OGD/R (P<0.05), reduced the polarization of BV2 cells to M1 type (P<0.05). Upadacitinib significantly decreased the migration ability of BV2 cells induced by OGD/R (P<0.05), reduced the inflammatory factors secreted by BV2 cells induced by OGD/R: IL-1β, IL-6, TNF-α (P<0.05). Upadacitinib increased the survival rate of co-cultured PC12 cells (P<0.05). Upadacitinib significantly inhibited the expression levels of p-JAK1 and p-STAT6 proteins in BV2 cells activated by OGD/R induction (P<0.05). Conclusion Upadacitinib decreases polarization of BV2 induced by OGD/R to M1 type and reduces inflammation, which is related to JAK1/STAT6 pathway.
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Objective:To report our experience in successful limb salvage in 2 cases of femoral fracture of Gustilo type ⅢC after warm ischemia beyond 10 hours.Methods:From February 2016 to April 2017, 2 patients with femoral fracture of Gustilo type ⅢC were treated at The Great Wall Orthopaedic and Hand Surgery Hospital after warm ischemia beyond 10 hours.Both of them were male, 42 and 27 years of age.After debridement, bone shortening for 8.0 cm and 10.0 cm respectively was followed by replantation. The fractures were fixated end to end with a compression plate, the femoral artery was anastomosed directly and the muscles were sutured end to end.Secondary osteotomy was conducted 4 months after successful replanta-tion, followed by unilateral external fixation for reconstruction.Limb lengthening began one week after sec-ondary osteotomy.The efficacy was assessed by the Paley criteria.Results:Scattered irregular necrosis occurred in the leg muscles but was cured by dermatoplasty through a decompressive incision 40 days after debridement for 4 times.The affected limbs in the 2 cases were successfully saved and lengthened to the same length as the opposite one.The limbs were lengthened for 8.0 and 10.0 cm and for 3.0 and 3.5 months, respectively.The unilateral external fixator was worn for 29 and 24 months, respectively.The plantar sensation recovered to S4 one year after operation.Follow-up at 6 months after removal of external fixation showed excellent bony outcomes and good functional outcomes in both cases According to the Paley criteria.Conclusion:For femoral fracture of Gustilo type ⅢC after warm ischemia beyond 10 hours, thorough debridement, plate fixation, bone shortening and replantation at one stage, followed by secondary limb lengthening using unilateral external fixation, may be practical and effective procedures, as long as in-dications for limb salvage should be comprehensively followed.
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Objective To establish a high-throughput in-vitro screening cell model for anti-atherosclerosis leading compounds.Methods Hypoxia response element (HRE) was cloned into a luciferase reporter vector, pGL3-Enhancer, to construct pGL3-HIF-1α-HRE.The THP-1human monocyte cell line was infected with the pGL3-HIF-1α-HRE and a stable cell line, THP-1-HIF-1α-HRE, was screened.Results Real-time PCR assay showed that HIF-1αexpression and luciferase activity in THP-1-HIF-1α-HRE cells was effectively upregulated by hypoxia.The increase of HIF-1αexpression and luciferase activity induced by hypoxia was significantly inhibited by lovastatin or curcumin.Conclusion THP1-HIF-1α-HRE, an in-vitro cell model for high-throughput screening lead compounds for anti-atherosclerosis (AS) was successfully established.
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Objective To explore the efficacy of temporary titanium plate screwing for positional maintenance in reduction and internal fixation for displaced acetabular fractures.Methods A retrospective study was conducted of the 28 patients (28 hips) with displaced acetabular fracture who had been treated by open reduction and internal fixation from October 2013 to March 2016.They were 20 males and 8 females,aged from 24 to 68 years (average,42.3 years).The time from injury to surgery ranged from 7 to 21 days(average,14.5 days).According to the Letournel-Judet classification,there were 2 posterior column fractures,4 transverse fractures,5 posterior column plus posterior wall fractures,6 transverse plus posterior wall fractures,2 T-shaped fractures,3 anterior and posterior transverse fractures and 6 double column fractures.The posterior acetabular approach or combined anterior and posterior approach was used.In all the patients temporary titanium plate screwing was conducted to fix one side of the fracture so as to facilitate accomplishment of open reduction and internal fixation without losing the indirect anatomic reduction of the intraarticular fracture.After the open reduction and internal fixation was accomplished,the temporary screw fixation was removed in 26 patients but retained in 2 patients as needed.The reduction quality,complications and outcomes at the final follow-ups were recorded.Results All the 28 patients were followed up for 10 to 36 months (mean,15.6 months).By the Matta criteria,anatomical reduction was achieved in 26 cases,unsatisfactory reduction in one and poor reduction in one,yielding an anatomic reduction rate of 92.9％.By the improved Mere d'Aubigne & Postel criteria,the clinical outcomes at the final follow-up were excellent in 27 cases and good in one,yielding a good to excellent rate of 100％.Postoperatively,heterotopic ossification of different severities occurred in 11 cases but did not affect their joint function;transient paralysis of the sciatic nerve was reported in 6 cases but recovered 3 months after surgery.No complications like avascular necrosis of the femoral head or walking pain were observed during follow-ups.Conclusion Temporary fixation with titanium plate screws during open reduction and internal fixation for displaced acetabular fractures can effectively improve the reduction and fixation of the articular surface,leading to satisfactory short-term clinical outcomes.
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Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations (at ∼80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1 cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.
الموضوعات
Humans , Anilides , Pharmacology , Basal Cell Nevus Syndrome , Hedgehog Proteins , Genetics , Pharmacology , Molecular Targeted Therapy , Odontogenic Cysts , Genetics , Therapeutics , Odontogenic Tumors , Genetics , Therapeutics , Pyridines , Pharmacologyالملخص
Objective To study the protective effect of Fu-Yuan-Xing-Nao decoction (FYXND) on rats with middle cere-bral ischemia reperfusion injury .Methods Male Sprague-Dawley rats were randomly divided into sham ,ischemia-reperfusion , and low ,middle ,high FYXND dose (5 .5 ,11 ,22 g/kg) groups .Rats model was induced by 2 h of middle cerebral artery oc-clusion and 24 h reperfusion .The neurological deficit score of each group was evaluated .The infarct size was measured by the 2 ,3 ,5-triphenyltetra-zolium(TTC) chloride staining assay .The pathological changes of brain tissue were observed by HE stai-ning assay .The changes of Nissl bodies were observed by Nissl staining .Tunnel staining was used to observe the apoptosis of neurons in brain .Serum levels of superoxide dismutase (SOD)and Malondialdehyde (MDA ) were measured .Results Com-pared with the model group ,neurological outcomes were improved in all three groups of low ,middle and high FYXND dose (5 .5 ,11 ,22 g/kg) .Significantly reduced infarct brain volume was observed with TTC staining in all three FYXND groups . The results from HE staining assay indicated that the pathological structure of brain tissue was improved in the treatment groups .The numbers and morphology of Nissl corpuscles in the treated group were also improved based on the results of Nissl staining .Both the Tunnel staining positive cells and the rate of apoptosis were decreased .Compared with the model group , FYXND increased the rat serum SOD level and decreased the MDA level .Conclusion FYXND has protective effects on cere-bral ischemia reperfusion injury in rats .
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Tanshinone ⅡA is a kind of phenanthraquinone derivatives derived from Salvia miltiorrhiza,which is one of the main active components of Danshen to play the protective role of cerebral ischemic injury.Inflammation plays an important role in the pathogenesis of cerebral ischemia.In recent years,much evidence shows that immune cells,adhesion molecules,in-flammatory mediators have been involved in the pathogenesis of immune response in the central nervous system through induc-tion or regulation of cerebral ischemia.In this paper,the research progress of mechanism of inflammatory response of tanshi-none ⅡA after cerebral ischemia was reviewed,which provided a new idea for the study of the protective mechanism of tanshi-none ⅡA in cerebral ischemia.
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Objective To study the extraction technology and optimize the extraction process of Fuyuan Xingnao gran-ule.Methods The preliminary extraction process was designed by routine extraction method combined with the results of pharmacological activity experiment.The extraction process was optimized with orthogonal test.Results The extract was ob-tained by ethanol reflux extraction,water decoction extraction or ethanol precipitation followed by filtration and concentration. The optimal process for ethanol reflux extraction was extracting twice with 50% ethanol.The ratio of liquor to dry material was 8∶1 for the first time and 6∶1 for the second time.The extraction time was 120 minutes for the first time and 80 minutes for the second time.The optimal process for water decoction extraction was extracting twice with 120 minutes and 80 minutes each time.The ratio of liquor to dry material was 10∶1 for the first time and 8∶1 for the second time.The extraction temper-ature was100 ℃.The best ethanol precipitation process was 16 hour extraction with 80% ethanol.The ratio of ethanol to dry material was 2∶1.Conclusion The quality of Fuyuan Xingnao granule extract with this optimized extraction process was in line with requirements of Pharmacopoeiaof the People's Republic of China 2015,4 Volumes(0104 granule).
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Objective To investigate the feasibility and clinical effect of Kocher-Langebeck (K-L) approach without cutting the short external rotator muscles of hip for treatment of cetabular posterior column fractures.Methods A retrospective case series study was performed on 28 patients with acetabular fractures admitted from June 2015 to February 2017.There were 23 males and 5 females,averagely aged 43.6 years (range,26-71 years).According to the Letournel classification,there were 9 patients with simple fractures,14 back wall and back pillar fractures and 5 cross fractures.All patients were combined with posterior dislocation.The patients were given tibial tubercle traction after hip joint reduction in the hospital.During the surgery,K-L approach was adopted without cutting the short external rotator muscles of hip.Operation duration and intraoperative bleeding were recorded.Visual analogue score (VAS) was recorded before and after operation.The X-ray at 1 day,6 weeks,3 months and 1 year after operation were reviewed to evaluate fracture healing time.Matta criteria were used to assess the surface flatness of joint.The modified Merle d'Aubigné-Postel scoring system was applied to evaluate the function of hip joint.Intraoperative and postoperative complications were recorded.Results The operation duration was 76-120 min (mean,94 min),and the intraoperative blood loss was 120-320 ml (mean,265 ml).All patients were followed up for average 16 months (range,10-24 months).Preoperative VAS was 5-10 points [(7.5 ± 1.3) points],and 0-3 points [(0.9 ± 0.8) points] 6 months after operation (P ＜ 0.01).All fractures healed and the average healing duration was 10.1 weeks (range,6-12 weeks).According to the Matta criteria,24 patients were graded excellent and 4 good,with excellence rate of 100％.According to the modified Merle d'Aubigné-Postel grading system,clinical results were graded excellent in 23 patients,good in 5,with excellence rate of 100％.Transient sciatic nerve injury occurred in 3 patients after surgery,and the nerve function of these patients fully recovered within 3 months after operation.There were no infection,heterotopic ossification and other complications.The wound healing was good,without liquefaction or cracking.Sciatic nerve injury was found in five patients,three of whom were performed with a transient lesion and recovered within 3 months.Conclusion In the posterior pathway surgery for acetabular posterior column fractures,the K-L approach without cutting the short external rotator muscles of hip can be used to complete the internal fixation with a high rate of fracture healing,sound reduction outcome,satisfactory functional recovery and few complications.
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Objective To explore the application of micro screws in holistic management of comminuted fracture of posterior acetabular wall combined with posterior hip dislocation.Methods From October 2013 to March 2016,38 patients (38 hips) were managed for comminuted fracture of posterior acetabular wall combined with posterior hip dislocation.They were 29 males and 9 females,aged from 15 to 71 years (average,38.6 years).According to the Letournel-Judet classification,there were 35 simple fractures of posterior acetabular wall and 3 complex fractures (2 fractures of posterior column plus posterior wall and one transverse plus posterior wall fracture).All fractures were comminuted and involved the posterior wall.The posterior Kocher-Langenbeck approach was selected for all the patients.Intraoperative exploration revealed the comminuted posterior walls were complicated with broken acetabular rims and ruptured glenoid rims to various degrees.Micro screws or micro screw-plate system were used to repair the comminuted fractures and broken acetabular rims,bridge support fixation with a locking plate followed pelvic reconstruction,and at the same time the ruptured glenoid rims were sutured so that the whole posterior articular structure around the posterior wall was repaired and reconstructed in a holistic manner.Results All the 38 patients were followed up for 12 to 36 months (average,17.6 months).By the Matta assessment,the reduction was excellent in 36 cases and fine in 2,giving an excellent to good rate of 100％.All fractures got united after 9 to 14 weeks (average,10.2 weeks).By the improved Merle d'Aubigne & Postel criteria,the clinical outcome was excellent in 35 cases and good in 3,giving an excellent to good rate of 100％.After surgery,heterotopic ossification occurred in one case,and transient paralysis of the sciatic nerve in 3 cases.No infection,necrosis of the femoral head,joint pain,joint malfunction or unstable walking was observed.Conclusion In the management of comminuted fracture of posterior acetabular wall combined with posterior hip dislocation,the lesions of the whole posterior wall can be repaired primarily in a holistic manner by repairing the shattered posterior wall of the acetabulum wth micro plate and screw system and simultaneous suture and fixation of the broken actabular rim and ruptured glenoid rim.
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Objective To investigate effectiveness of the modified Kocher-Langenbeck (K-L) approach for acetabular fractures.Methods A consecutive series of 58 patients with acetabular fracture were treated operatively from January 2013 to December 2016.They were divided into 2 groups according to the approaches used.In the experimental group of 30 patients (25 males and 5 females with an average age of 42.6 ± 13.8 years),the modified K-L approach was used not to dissect the external rotation short muscles and the anterior approach was also used when necessary.In the control group of 28 patients (24 males and 4 females with an average age of 45.2 ± 10.2 years),the traditional K-L approach was used and in combination with the anterior approach when necessary.The 2 groups were comnpared in terms of operation time,intraoperative blood loss,reduction,fracture union time and functional recovery of the affected hip at the last follow-up.Results The experimental group reported significantly shorter operation time (94.2 ± 32.8 min) and significantly less intraoperative bleeding (220.8 ± 96.7 mL) than the control group (135.8 ± 88.0 min and 405.5 ±95.7 mL) (P ＜ 0.05).According to the Matta's criteria for reduction,the experimental group had 24 excellent,4 good and 2 fair cases (an excellent to good rate of 93.3％) while the control group had 20 excellent,3 good and 5 fair cases (an excellent to good rate of 82.1％),showing no significant differences between the 2 groups (P ＞ 0.05).All the 58 patients obtained follow-up for 6 to 24 months (average,16 months).The fracture union time was 10.1 ± 1.9 weeks for the experimental group and 9.9 ±2.1 weeks for the control group,showing no significant differences between the 2 groups (P ＞ 0.05).According to the modified Merle d'Aubigne & Postel scoring for the functional recovery of the affected hip at the last follow-up,the experimental group had 23 excellent,5 good and 2 fair cases (an excellent to good rate of 93.3％) while the control group had 12 excellent,6 good,6 fair and 4 poor cases (an excellent to good rate of 64.2％),showing a significant difference between the 2 groups (P ＜ 0.05).Conclusion Compared with the traditional K-L approach,the modified K-L approach has advantages of small trauma,less hemorrhage and good postoperative recovery so that it can be a good choice among the posterior approaches for acetabular fractures.
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People do have some risks of exposing to the radiation during their daily life .Longtime or megadose ionizing radiation can induce tissue damage ,which is related to cell apoptosis ,necrosis and inflammation ,etc ..Currently ,more and more radio protective agents were developed and several signaling pathways were involved .NFκB ,MAPK ,PI3k/Akt ,p53 and STAT3 signaling pathways were reviewed in this article .
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Objective To evaluate the efficacy of Scrophularia ningpoensis granules combined with fosinopril in treatment of congestive heart failure.Methods 60 congestive heart failure patients were randomly divided into 2 groups, 30 patients in the treatment group and 30 patients in the control group.Besides the conventional therapy, the control group was treated with fosinopril and the treatment group received Scrophularia ningpoensis granules plus fosinopril for 90 days.Left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and serum B-type brain natriuretic peptide (BNP) were measured before and after treatment.Results The total effective rate in the treatment group and the control group were 90%, but significantly effective number in the treatment group was higher than the control group.The levels of BNP, LVEDD and LVESD in both groups were decreased, while LVEF was increased after the treatment.The difference was statistically significant (P<0.01).The degree of improvement of heart function in the treatment group was better than that in the control group (P<0.05).Conclusion The combination therapy of Scrophularia ningpoensis granules and fosinopril is efficacious in treating CHF.
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Traumatic brain injuries(TBI) have caused severe injuries and deaths all over the world ,but so far research-ers have not found an effective drug in treating TBI on clinic .However ,peptides have gradually been in a hot research with its advantages which include safety and tolerance etc .The neuroprotective and anti-inflammatory effects of several peptide com-pounds in traumatic brain injury are reviewed in this paper .
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Oral and maxillofacial development is the course that the oral students first learn, and their mastery directly influences the study of other courses that follow. The application of mind mapping in the teaching of the development of oral maxillofacial region can make the temporal and spatial features of oral and maxillofacial development in the form of visual presentation, help students build development mode of thinking, stimulate students' interest in learning, improve the quality of teaching of oral histopathology, and promote the new teaching concept in oral pathology teaching.