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Objective:To investigate genetic variation profiles of δ-globin (HBD gene) and hematological phenotypes in Guangdong population.Methods:Retrospective case analysis was performed in this study. Blood samples of 11 616 couples who participated in free thalassemia screening in Guangzhou from July 2020 to December 2022 were collected which underwent blood routine tests and hemoglobin (Hb) capillary electrophoresis. According to the results, 154 samples were enrolled in this study: (1)group of 35 cases with HbA 2 <2.0% but no HbF band; (2)group of 64 cases with HbA 2 < 2.0% and HbF band; (3)group of 25 cases with HbA 2 <2.0% and suspected HbA 2 variants; (4) group of 25 cases with HbA 2 ≥2.0% and <3.5% and HbF band, as well as abnormal blood routine report [mean corpuscular volume (MCV) <82 fl and/or mean corpuscular hemoglobin (MCH) <27 pg]; (5)group of 5 cases with HbA 2 ≥2.0% and <3.0% accompanied with β thalassemia gene carriers Sanger sequencing was used to detect single nucleotide variants of δ-globin. Results:(1) A total of 22 genetic variations were detected, including 6 de novo variations, and the top 3 genetic variations were respectively c.-127T>C (57.02%, 65/114), c.-80T>C (9.65%, 11/114), c.349C>T (7.89%, 9/114). (2) In group of patients with HbA 2 <2.0% but no HbF band, 22 cases (62.85%, 22/35) had HBD gene variation, including 7 cases with MCV and MCH lower than reference values, 4 cases with α thalassemia; 13 cases had no HBD gene variation, including 12 cases with lower MCV and MCH. Among 19 cases with abnormal blood routine test results, levels of HbA 2 in patients (7 cases) with HBD gene variation were lower compared with those without HBD gene variation (12 cases) ( P<0.01%). (3)In group of patients with HbA 2<2.0% with HbF band, 59 cases (92.18%, 59/64) had HBD gene variations whose mutations all occurred in promoter region, and the HbF were all lower than 5.0%; 5 cases with HbF >5.0% had no HBD gene variation. (4) In group of patients with HbA 2 <2.0% and suspected HbA 2 variants, the detection rate was 100% (25/25) and δ-globin variants <1.0%. (5) In group of patients with HbA 2 ≥2.0% and <3.5% and HbF band accompanied with abnormal blood routine results, no HBD gene variation was found. (6) In group of 5 patients with HbA 2 ≥2.0% and <3.0% with β thalassemia gene carriers, HBD gene variation were found in all cases, and the level of HbA 2 was (2.62±0.17)% and HbF was (3.62±2.22)%. Conclusions:There are various genotypes of HBD gene variation, among which HBD: c.-127T>C is the most common in Guangdong population in China. Mutations in the promoter region may cause decrease in HbA 2 and increase in HbF which is mostly less than 5% but exceeds 5.0% when combined with β thalassemia. Our study enriched the gene mutation profiles of HBD gene in Guangdong population.
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Objective To observe the effects of tetrandrine on the proliferation,migration,and invasion of melanoma cell B16,and to explore its effects on epithelial mesenchymal transition(EMT)and potential regulatory mechanisms.Methods(1)The proliferation of B16 cells was detected by CCK-8 assay after 0,2,4,6,8 and 10 μmol·L-1 of tetrandrine intervention for 24 and 48 hours.The colony formation ability of B16 cells was detected by plate clone formation assay after 1,2 and 4 μmol·L-1 of tetrandrine intervention;the migration and invasion ability of B16 cells was detected by cell scratch assay and Transwell invasion assay;the expressions of N-cadherin,Vimentin and E-cadherin related to EMT in B16 cells were detected by Western Blot assay.The mouse melanoma lung metastasis model was replicated by tail vein injection of B16 cells to observe the effects of tetrandrine(50 and 100 mg·kg-1)administered by gavage on the number of metastatic tumor nodules in the lungs of mice.(2)The CTD,SwissTargetPrediction and Similarity Ensemble Approach databases were used to predict the targets of tetrandrine;the GeneCards database was used to search for targets related to melanoma disease;the intersection of these two databases was taken as the potential target of tetrandrine for melanoma treatment.The intersected targets were imported into STRING database to construct protein-protein interaction(PPI)network and screen the core targets;the intersected targets were imported into DAVID database for GO function and KEGG pathway enrichment analysis;and molecular docking between tetrandrine and the core targets was verified by Autodock software.(3)In vivo experimental validation:after intervention of 1,2 and 4 μmol·L-1 tetrandrine,Western Blot method was used to detect the expression of the key pathway AKT/NF-κB/CREB pathway-related proteins;and AKT agonist SC79 was used to validate the replication experiments.Results(1)The IC50 of B16 cells intervened by tetrandrine was 4.273 and 4.085 μmol·L-1 at 24 and 48 hours.Compared with the control group,the colony forming ability,scratch healing rate and invasion rate of cells in the 1,2 and 4 μmol·L-1 tetrandrine group were all significantly reduced(P<0.05,P<0.01,P<0.001);the expressions of cellular Vimentin and N-cadherin protein expressions were significantly down-regulated(P<0.01,P<0.001),and E-cadherin protein expression was significantly up-regulated(P<0.01,P<0.001).Compared with the model control group,the number of melanoma lung metastatic nodules was significantly reduced in the mice in the high-dose group of tetrandrine(P<0.05).(2)A total of 60 potential targets were obtained for the treatment of melanoma with tetrandrine;core targets such as AKT1,TNF,CCND1,RELA,CASP9,CHUK,and CREBBP were further screened,among which AKT1 was the most strongly interacting target;the signaling pathways such as apoptosis,FoxO,TNF,PI3K-AKT,and NF-κB were mainly involved.The molecular docking showed that tetrandrine had strong binding activity with AKT1,TNF,RELA and other core targets.Compared with the control group,protein expressions of p-AKT/AKT,p-NF-κB p65/NF-κ B p65,and p-CREB/CREB were significantly down-regulated in the cells of the tetrandrine 1,2,and 4 μmol·L-1 groups(P<0.05,P<0.01);protein expressions of p-AKT and p-NF-κB p65 were significantly up-regulated in the cells of the SC79 group(P<0.001).Compared with the SC79 group,protein expressions of p-AKT,p-NF-κB p65,and p-CREB were significantly down-regulated in the cells of the 2 μmol·L-1 tetrandrine+ SC79 group(P<0.001).Conclusion Tetrandrine may inhibit the proliferation,migration,invasion and EMT of mouse melanoma by regulating the AKT/NF-κB/CREB pathway,and thus inhibit the lung metastasis of mouse melanoma.
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Axonal demyelination is an important factor causing neurological dysfunction after spinal cord injury. Retaining the integrity of myelin sheath and promoting remyelination play an important role in the functional recovery of spinal cord injury. The bottleneck of the failure of remyelination is the inability of myelin-forming cells (oligodendrocytes and Schwann cells) to differentiate and mature. In recent years related research on spinal cord injury demyelination has found that cell transplantation, neuregulin-1 and hydrogel can effectively enhance remyelination, and identified aquaporin-4 (aquaporin-4, AQP4), metal-loproteinase (Matrix metailoproteinase, MMP) may be a potential therapeutic target to promote myelin recovery after spinal cord injury. This review discusses the research progress of enhancing remyelination after spinal cord injury, providing ideas for the further development of new methods for the treatment of spinal cord injury.
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Objective: To assess the effectiveness of transanal drainage tube (TDT) in reducing the incidence of anastomotic leak following anterior resection in patients with rectal cancer. Methods: We conducted a systematic search for relevant studies published from inception to October 2022 across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. Meta-analysis was performed using Review Manager 5.4 software. The primary outcomes included total incidence of anastomotic leak, grade B and C anastomotic leak rates, reoperation rate, anastomotic bleeding rate, and overall complication rate. Results: Three randomized controlled trials involving 1115 patients (559 patients in the TDT group and 556 in the non-TDT group) were included. Meta-analysis showed that the total incidences of anastomotic leak and of grade B anastomotic leak were 5.5% (31/559) and 4.5% (25/559), respectively, in the TDT group and 7.9% (44/556) and 3.8% (21/556), respectively, in the non-TDT group. These differences are not statistically significant (P=0.120, P=0.560, respectively). Compared with the non-TDT group, the TDT group had a lower incidence of grade C anastomotic leak (1.6% [7/559] vs. 4.5% [25/556]) and reoperation rate (0.9% [5/559] vs. 4.3% [24/556]), but a higher incidence of anastomotic bleeding (8.2% [23/279] vs. 3.6% [10/276]). These differences were statistically significant (P=0.003, P=0.001, P=0.030, respectively). The overall complication rate was 26.5%(74/279) in the TDT group and 27.2% (75/276) in the non-TDT group. These differences are not statistically significant (P=0.860). Conclusions: TDT did not significantly reduce the total incidence of anastomotic leak but may have potential clinical benefits in preventing grade C anastomotic leak. Notably, placement of TDT may increase the anastomotic bleeding rate.
Subject(s)
Humans , Anastomotic Leak/etiology , Rectal Neoplasms/complications , Drainage , Anastomosis, Surgical/adverse effects , Reoperation/adverse effects , Hemorrhage , Retrospective StudiesABSTRACT
The correct alignment of the knee joint is considered to be one of the most influential factors in determining the long-term prognosis after total knee arthroplasty(TKA). In order to achieve the correct alignment goal, many different alignment concepts and surgical techniques have been established. For example, mechanical alignment(MA), kinematic alignment(KA) and functional alignment(FA) have their own characteristics. MA focuses on achieving neutral alignment of the limbs, parallel and equal bone gaps during stretching and flexion. KA aims to restore the patient 's natural joint line, make the joint level and angle normal and improve the physiological soft tissue balance, and strive to reproduce the normal knee function;among them, functional alignment(FA) developed with robot-assisted surgery technology is a relatively new alignment concept. It not only considers the alignment of the body, but also aims to achieve flexion and extension balance, while respecting the native soft tissue capsule. It not only restores the plane and slope of the in situ joint line accurately during the operation, but also takes into account the balance of soft tissue, which is a better alignment method. Therefore, it is of great significance to correctly construct the lower limb force line of patients, which is helpful to restore knee joint function, relieve pain symptoms and prolong the service life of prosthesi. However, compared with traditional TKA, the operation time of robot-assisted FA-TKA is prolonged, which means that the probability of postoperative infection will be greater. At present, most studies of FA technology report short-term results, and the long-term efficacy of patients is not clear. Therefore, long-term research results are needed to support the application of this technology. Therefore, the author makes a review on the research status of functional alignment.
Subject(s)
Humans , Arthroplasty, Replacement, Knee/methods , Robotics , Knee Joint/surgery , Osteoarthritis, Knee/surgery , Knee , Knee Prosthesis , Biomechanical PhenomenaABSTRACT
Objective: To investigate the effect and its underlying molecular mechanisms of essential oil from Saussurea costus in esophageal cancer cell line Eca109. Methods: The chemical composition of essential oil from Saussurea costus was investigated by gas chromatography-mass spectrometry (GC-MS). The anti-proliferative, anti-migrative, and apoptotic effects of essential oil from Saussurea costus against Eca109 cells were analyzed. Moreover, the expression of proteins associated with cell cycle, metastasis, and apoptosis was determined. Results: GC-MS analysis showed that essential oil from Saussurea costus was predominantly comprised of sesquiterpenes. Saussurea costus essential oil inhibited the viability of Eca109 cells in a dose-and time-dependent manner with IC 50 values of (24.29±1.49), (19.16±2.27) and (6.97±0.86) μg/mL at 12, 24, and 48 h, respectively. The expression levels of target proteins in the cell cycle (phase G 1 /S), including cyclin D1, p21, and p53, were affected by Saussurea costus essential oil. The essential oil also downregulated the expression of metastasis-related proteins MMP-9 and MMP-2. Moreover, it induced apoptosis of Eca109 cells through the mitochondrial pathway, as well as inhibition of STAT3 phosphorylation. Conclusions: The essential oil from Saussurea costus exhibited anti-proliferative, anti-migrative, and apoptotic effects on Eca109 cells, and could be further explored as a potential anti-esophageal cancer agent.
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[Abstract] Objective To investigate the effects of the downregulation of draxin expression on the projection characteristics of 23C10-positive neural fibers in the chick embryonic hindbrain. Methods The vitro incubation of HH stages 21-22 chick embryonic hindbrain biopsy with alkaline phosphatase (ALP) protein was used as control group. The incubation of HH stages 21-22 chick embryonic hindbrain biopsy with draxin-ALP fusion protein was used as experimental group. The number of embryonic hindbrain for each group was 10. To detect whether 23C10-positive neural fibers could directly bind to draxin protein or not;In ovo electroporation using empty vector in the chick embryonic hindbrain was used as control group. In ovo electroporation with small interfering RNA(siRNA) expressing vector for reducing draxin expression in the chick embryonic hindbrain was used as experimental group. The number of embryonic hindbrain for each group was 18. The effect of the down-regulation of draxin expression and the change of projection characteristics of 23C10-positive neural fibers were observed to check whether the down-regulation of draxin expression would affect the distribution of 23C10-positive fibers. Results Most portion of draxin protein could overlap with 23C10-positive neural fibers in HH stages 21-22 chick embryonic hindbrain biopsies; After expression of the siRNA plasmid against draxin by electroporation, the expression level of draxin protein was significantly reduced, and the distribution of 23C10-positive fibers was scattered in the dorsal hindbrain on the electroporated side at HH stages 25-26 of chick embryos (P < 0. 05) . Conclusion Draxin protein may directly bind to 23C10-positive fibers in hindbrain, and it plays an important regulatory role in the fasciculation of 23C10-positive fibers during chick embryonic development.
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Treatment and rehabilitation of spinal cord injury has been a major problem in the medical field‚ and little progress has been achieved in the improvement of neuronal function following injury. Secondary damage is the main cause of neurological dysfunction after spinal cord injury‚ and inflammation is the most important pathological process in the secondary injury stage. In the acute phase‚ it is believed that the reduction of secondary damage by inhibiting neuroinflammation can reduce the damage of nerve function and achieve neuroprotection. The inflammasome is a type of protein complex‚ which is assembled and named by the receptor proteins of the NLRs family and the PHYIN family of pattern recognition receptors as the main framework. Common inflammasomes include NLRP1‚ NLRP3‚ NLRC4 (IPAF)‚ and AIM2 etc. When infected or stimulated by injury‚ inflammasomes assemble in the cytoplasm and activate the pro-inflammatory protease caspase-1. Activated caspase-1 promotes the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18 on the one hand‚ and mediates pyroptosis on the other hand. Pyroptosis is a way of programmed cell death induced under pathological conditions of inflammation and stress. Cell swelling and rupture and the release of cell contents are its main characteristics. Both pro-inflammatory cytokines and intracellular substances released by pyroptosis can be used as pro-inflammatory signals to trigger an inflammatory response. Recently‚ it has been discovered that inflammasomes participate in the activation of the inflammatory cascade after spinal cord injury by inducing the release of pro-inflammatory factors and mediating pyroptosis‚ and then aggravate secondary neuroinflammation. Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response‚ promote the survival of nerve cells‚ and achieve neuroprotective effects. Therefore‚ the inflammasome is expected to become a new target for the treatment of spinal cord injury. This article reviewed the structure of the inflammasome and its role in spinal cord injury‚ activation mechanism and treatment‚ which may provide ideas for the follow-up research.
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A spinal cord injury is a serious disease, and there is currently no effective treatment. The inflammatory reactions start within a few hours after damages to spinal cord tissues and peak within a few days and they may continue for several years. Reducing the inflammatory response after the spinal cord injury is one of the important treatment strategies. Butyrate and β-hydroxybutyrate are two closely related substances. They have similar structures and differ in only one hydroxyl group. They have attracted widespread attention because of their good anti-inflammatory properties in many diseases. Recently it has been demonstrated that butyrate and β-hydroxybutyrate can inhibit the activity of the NF-κB / NLRP3 inflamma-some signaling pathway and reduce the expression of pro-inflammatory factors; or by enhancing the level of antioxidant molecules, it can reduce the inflammatory response after spinal cord injury. Therefore, butyrate and β-hydroxybutyrate may be promising treatments after a spinal cord injury. Here we review the structure and production of butyrate and β-hydroxybutyrate, the mechanism of anti-inflammatory effects in a spinal cord injury, and the treatment prospects, in order to provide theoretical references for researchers in this field.
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Objective: To investigate the effect and its underlying molecular mechanisms of essential oil from Saussurea costus in esophageal cancer cell line Eca109. Methods: The chemical composition of essential oil from Saussurea costus was investigated by gas chromatography-mass spectrometry (GC-MS). The anti-proliferative, anti-migrative, and apoptotic effects of essential oil from Saussurea costus against Eca109 cells were analyzed. Moreover, the expression of proteins associated with cell cycle, metastasis, and apoptosis was determined. Results: GC-MS analysis showed that essential oil from Saussurea costus was predominantly comprised of sesquiterpenes. Saussurea costus essential oil inhibited the viability of Eca109 cells in a dose-and time-dependent manner with IC 50 values of (24.29±1.49), (19.16±2.27) and (6.97±0.86) μg/mL at 12, 24, and 48 h, respectively. The expression levels of target proteins in the cell cycle (phase G 1 /S), including cyclin D1, p21, and p53, were affected by Saussurea costus essential oil. The essential oil also downregulated the expression of metastasis-related proteins MMP-9 and MMP-2. Moreover, it induced apoptosis of Eca109 cells through the mitochondrial pathway, as well as inhibition of STAT3 phosphorylation. Conclusions: The essential oil from Saussurea costus exhibited anti-proliferative, anti-migrative, and apoptotic effects on Eca109 cells, and could be further explored as a potential anti-esophageal cancer agent.
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OBJECTIVES@#Electroacupuncture can enhance autophagic flow, promote neuronal regeneration, axonal and myelin remodeling to achieve the protection of spinal cord injury, but its role in neurogenic urine retention is not completely clear. This study aims to investigate whether the mechanism of electroacupuncture in the treatment of neurogenic urine retention is through autophagy mediated by adenosine monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.@*METHODS@#A rat model of neurogenic urine retention after sacral spinal cord injury was established. The rats with successful model were randomly divided into a model group, an electroacupuncture group (electro-acupuncture for Ciliao, Zhongji, and Sanyinjiao by electronic stimulation, once a day, 20 min each time for 7 days), and an electroacupuncture+AMP-activated protein kinase (AMPK) inhibitor group (on the basis of the treatment of electroacupuncture group, 100 μg of AMPK inhibitor compound C was injected intramuscularly around the L2-3 intervertebral space on the 1st and 4th day). The normal group did not receive any treatment. The maximum bladder volume, bladder basal pressure, leak point pressure, and bladder compliance were recorded by multi-channel physiological recorder; the morphology of bladder tissue was observed by HE staining; autophagy was observed under transmission electron microscope; the expressions of LC3II and Beclin1 protein were observed by immunofluorescence staining; the protein levels of AMPK, phosphorylated-AMPK (p-AMPK), mTOR, phosphorylated-mTOR (p-mTOR), microtubule associated protein 1 light chain 3 (LC3) II and Beclin1 in bladder tissue were detected by Western blotting.@*RESULTS@#Compared with the normal group, the maximum bladder capacity, leak point pressure, bladder compliance, p-AMPK, LC3II, Beclin1 protein expressions in the bladder tissue of the model group increased, and the p-mTOR protein expressions were decreased (all P<0.05); compared with the model group, the maximum bladder capacity, bladder compliance, p-mTOR protein expression in the bladder tissue of the electroacupuncture group were decreased, and the p-AMPK, LC3II, and Beclin1 protein expressions were increased (all P<0.05); compared with the electroacupuncture group, the maximum bladder capacity, bladder compliance, p-mTOR protein expression in the bladder tissue of the electroacupuncture+AMPK inhibitor group were increased, the p-AMPK, LC3II, and Beclin1 protein expressions were decreased (all P<0.05). In the model group, the bladder became larger, with unclear and varying degrees of degeneration, severe tissue damage and autophagosome appeared; the bladder of the electroacupuncture group was smaller than that of the model group, and all levels were clearly visible with autophagy bodies; the layers were slightly disordered and damaged in the electroacupuncture + AMPK inhibitor group.@*CONCLUSIONS@#Electroacupuncture can activate autophagy through AMPK/mTOR pathway, thereby reducing neurogenic urine retention caused by spinal cord injury.
Subject(s)
Animals , Rats , AMP-Activated Protein Kinases , Autophagy , Beclin-1 , Electroacupuncture , Mammals , Rats, Sprague-Dawley , Spinal Cord Injuries , TOR Serine-Threonine KinasesABSTRACT
Objective:To systematically evaluate the effect of targeting mitochondria on spinal cord injury animal models, and provide experimental evidence. Methods:Literatures about animal experiments of targeting mitochondria treatment for spinal cord injury were searched in PubMed, Web of Science, Web of Knowledge, CNKI and Wanfang database from establishment to February, 2021. Three researchers independently screened the literatures and extracted the data, and they were summarized by qualitative analysis. Results:Eleven animal experimental studies were enrolled, including 548 animals with spinal cord injury. Six studies selected male or female Sprague-Dawley rats, and the rats in eight studies weighed 150~275 g. The animal models of spinal cord injury in all studies focused on T9~T11 contusive spinal cord injury, but there were differences in the use of spinal cord strikers and striking strength. The type, time, frequency, concentration and dosage of intervention drugs were all different. Due to the large heterogeneity of the included studies in animal species, animal models and outcome measures, qualitative analysis was conducted. Conclusion:Targeting mitochondria for spinal cord injury in animals could promote the recovery of motor function, reduce the damaged spinal cord tissue and increase the remaining tissue, enhance the ability of anti-oxidation and anti-apoptosis, and enhance mitochondrial biogenesis. Limited by the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
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OBJECTIVE@#To identify differentiation related miRNA and evaluate roles of miRNA during ATRA induced myeloid differentiation.@*METHODS@#The small RNA sequencing was used to analyze differential expressed miRNAs in ATRA induced NB4 cells. Then the several up or down-regulated miRNA were selected as the research candidates. SgRNAs targeting the genome of each miRNA were designed and NB4 cells with inducible expression of Cas9 protein were generated. After transduced sgRNA into NB4/Cas9 cells, the mutation level by PCR and surveyor assay were evaluated. The cell differentiation level was investigated by surface CD11b expression via flow cytometry.@*RESULTS@#A total of 410 mature miRNAs which expressed in NB4 cells were detected out after treated by ATRA, 74 miRNAs were up-regulated and 55 were down-regulated miRNAs with DNA cleavage generated by CRISPR/Cas9 was assayed directly by PCR or surveyor assay, quantitative PCR showed that the expression of miRNA was downregulated, which evaluated that gene edition successfully inhibitied the expression of mature miRNA. MiR-223 knockout showed the myeloid differentation of NB4 significantly inhibitied, while miRNA-155 knockout showed the myeloid differentation of NB4 cells significantly increased.@*CONCLUSION@#CRISPR/Cas9 is a powerful tool for gene editing and can lead to miRNA knockout. Knockouts of miR-223 and miR-155 have shown a differentiation-related phenotype, and the potential mechanism is the integrative regulation of target genes.
Subject(s)
CRISPR-Cas Systems , Cell Differentiation , Gene Editing , MicroRNAs/genetics , Sequence Analysis, RNA , TretinoinABSTRACT
Objective:To investigate the changes of genus-level gut microbiome in patients with spinal cord injury and its significance in clinical rehabilitation. Methods:Fecal samples were collected from 23 patients with spinal cord injury (patients group) and 21 healthy volunteers (control group). Gut microbiome was detected by 16S rDNA high-throughput sequencing. Bioinformatics methods such as species composition analysis and Random Forest were used to analyze the distribution and difference of genus-level gut microbiome between two groups. Results:Compared with the control group, the increased important marker genera in the patients group were as follows: UBA1819, Ruminiclostridium 9, Ruminococcaceae NK4A214 group, Ruminococcus 2, Ruminococceae UCG-005, Ruminiclostridium 5, Flavonifractor belonging to Ruminococceae; Aglistes, dgA-11 gut group, Rikenaceae RC9 gut group belonging to Rikenellaceae; [Eubacterium] oxidoreducens group belonging to Lachnospiraceae; Intestinibacter belonging to Peptostreptococcaceae; Escherichia-Shigella belonging to Enterobacteriaceae; Tannerellaceae belonging to Parabacteroides (|U| > 1.962, P < 0.05). The decreased marker genera in the patients group was Fusobacterium of Fusobacteriaceae (|U| = -2.284, P < 0.05). Conclusion:There are significant differences of gut microbiome in spinal cord injury patients. The relative abundance of Ruminococcaceae relating to depression, Ruminococcus relating to central nervous system diseases, and enteropathogenic bacteria such as Escherichia-Shigella and Erysipelothrix increase; and the relative abundance of butyrate-producing bacteria and anti-inflammatory bacteria benefitting to the intestine decrease; which may play a role in clinic.
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Results and Conclusion A total of 236 authors were included, out of whom 49 authors published more than three papers, and high-yielding authors were mainly represented by Zeng Y S and Chen L. There were 162 countries/institutions involved, out of which 85 published more than three papers. Seventy-five journals were included, out of which Exp Neurol was the one with the most articles. There were 107 key words included, and the hot words were spinal cord injury, MSCs, transplantation, bone marrow, repair, and functional recovery, which formed six cluster groups. The trend was to extract and culture progenitor cells and induce their directional differentiation; mechanism of immune regulation, anti-inflammatory and nerve regeneration in the treatment of spinal cord injury by MSCs, as well as the research of tissue engineering technology, biological materials in this field. Objective:To analyze the research status and hotspots of mesenchymal stem cells (MSCs) for treatment of spinal cord injury in the past five years. Methods:The related literatures from 2014 to 2018 in Science Citation Index-Expanded (SCI-E) of Web of Science (WOS) were included. CiteSpace software was used to analyze the cooperation relationship of authors, countries and research institutions. The keywords were taken as nodes for co-occurrence analysis, cluster analysis, dynamic frontier evolution and burst analysis. The co-citation of journals and literatures were taken as nodes for analysis, meanwhile, the visual maps were drawn and the results were analyzed.
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Chinese herbal compound Nao-Fu-Cong (NFC) has been mainly used to treat cognitive disorders in Traditional Chinese Medicine (TCM). The present study aimed to investigate whether its neuroprotective effects might be related to the inhibition of JNK/CHOP/Bcl2-mediated apoptosis pathway or not. We randomly assigned STZ (60 mg·kg)-induced diabetic rats into control group, diabetic model group and NFC groups (low-dose, medium-dose and high-dose). The primary culture of hippocampal neurons were transferred into different culture media on the third day. The cells were then divided into control group, high-glucose group, NFC (low-dose, medium-dose and high-dose) groups, CHOP si-RNA intervention group, JNK pathway inhibitor SP600125 group and oxidative stress inhibitor N-acetylcysteine (NAC) group. NFC significantly improved the cognitive function of diabetic rats, and had neuroprotective effect on hippocampal neurons cultured in high glucose. Further research results showed that NFC could reduce the apoptosis of hippocampal neurons in rats with diabetic cognitive dysfunction. NFC had inhibitory effects on CHOP/JNK apoptosis pathway induced by high glucose, and also decreased the levels of ROS and increased the mitochondrial membrane potential. These suggested that the neuroprotective effect of NFC might be related to the inhibition of CHOP and JNK apoptotic signaling pathways, and the cross pathway between oxidative stress and mitochondrial damage pathway.
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The WD40 transcription factor family is a gene superfamily widely found in eukaryotes, which is closely related to plant growth and development regulation. It has been reported that the WD40 transcription factor was involved in the synthesis of anthocyanins, which is one of the vital components of safflower flavonoid compounds. In this study, 40 CtWD40 members in the safflower genome were identified though bioinformatics tools and gene expression analysis methods. According to the WD40 protein sequence and phylogenetic characteristics of Arabidopsis and other plants, the safflower CtWD40 family was classified into 7 subfamilies. Conservative motif analysis was used to reveal the specific conserved motifs and gene structures of each subfamily member, and there exist a certain degree of similarities in the conserved motifs and gene structure between the closely related family members. Subsequently, the search for cis-acting elements of gene promoters found CtWD40-specific promoter elements, revealing the metabolic pathways which may involve. Next, enrichment of function analysis was employed to analyze the functional categories and cellular localization of the CtWD40 protein. Furthermore, the interactions between CtWD40 proteins predicted its potential regulatory function. Finally, 19 members of the safflower CtWD40 subfamily were analyzed by qRT-PCR, the result showed the expression patterns of these members were different in diverse tissue and flowering period. This study provides a basis for the functional and expression research of the CtWD40 genes.
Subject(s)
Carthamus tinctorius , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Plant , Genome, Plant , Multigene Family , Phylogeny , Plant Proteins , Genetics , Transcription Factors , GeneticsABSTRACT
OBJECTIVE@#To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients.@*METHODS@#53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing.@*RESULTS@#21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy.@*CONCLUSION@#A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.
Subject(s)
Humans , Chromosomes, Human, Pair 11 , Hematopoietic Stem Cell Transplantation , In Situ Hybridization, Fluorescence , Leukemia, Myeloid, Acute , Mutation , Prognosis , fms-Like Tyrosine Kinase 3ABSTRACT
BACKGROUND@#Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis.@*METHODS@#We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12.@*RESULTS@#The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported.@*CONCLUSION@#During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Subject(s)
Humans , Double-Blind Method , Follow-Up Studies , Ointments , Psoriasis/drug therapy , Resorcinols , Severity of Illness Index , Stilbenes , Treatment OutcomeABSTRACT
OBJECTIVE@#To compare the clinical effects of ultrasonic subgingival debridement and ultrasonic subgingival debridement combined with manual root planing on severe periodontitis and then to investigate the necessity and significance of manual root planing.@*METHODS@#Twenty-three patients with severe periodontitis participated in this split-mouth randomized-controlled clinical trial. Baseline examination and randomization were performed after supragingival scaling: each of the upper and lower jaws had a quadrant as the test group treated with ultrasonic subgingival debridement combined with manual root planing, whereas the other two quadrants were the control group treated with ultrasonic subgingival debridement. Treatment of each patient was at intervals of one week and completed in two visits. Clinical indicators concerning probing depth (PD), clinical attachment loss (CAL) and bleeding index (BI) were recorded at baseline and 1 month, 3 months, 6 months after treatment.@*RESULTS@#There was no significant difference of periodontal indicators between the test group and the control group at baseline. Both the test group and control group resulted in significant improvement of PD, CAL and BI. One and three months after treatment, reduction of PD in the test group was higher than that in the control group [1 month: (2.13±1.31) mm vs. (1.79±1.33) mm, P<0.01; 3 months: (2.46±1.33) mm vs. (2.17±1.38) mm, P<0.01] and reduction of CAL in the test group was higher than that in the control group [1 month: (1.89±2.03) mm vs. (1.65±1.93) mm, P<0.01; 3 months: (2.03±2.05) mm vs. (1.83±1.97) mm, P<0.05]. Six months after treatment, PD in the test group and the control group decreased by (2.52±1.40) mm and (2.35±1.37) mm respectively, and the improvement in the test group was significantly better than that in the control group (P<0.01). CAL in the test group and the control group decreased by (1.89±2.14) mm and (1.77±2.00) mm respectively, and there was no statistical difference between the groups. There was no significant difference in the changes of BI between the two groups 1, 3 and 6 months after treatment.@*CONCLUSION@#Ultrasonic subgingival debridement combined with manual root planing has more reduction in PD and CAL compared with ultrasonic subgingival debridement. Therefore, it is still necessary to use manual instruments for root planing following ultrasonic subgingival debridement.