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Objective:To summarize the characteristics of genetic variation and prenatal diagnosis in pedigrees with X-linked adrenoleukodystrophy (X-ALD) and elucidate the value of prenatal diagnosis in preventing the birth of children with X-ALD.Methods:Twenty pedigrees, clinically diagnosed with X-ALD in Peking University First Hospital from November 2012 and March 2019, were included in this retrospective study. Genomic DNA was extracted from peripheral blood and amniotic fluid or chorionic villi samples of probands and their families for detecting variants in ATP-binding cassette subfamily D member 1 ( ABCD1) gene using polymerase chain reaction (PCR)-Sanger sequencing. Linkage analysis was also performed on five microsatellite markers near ABCD1 gene to exclude maternal contamination. Characteristics of ABCD1 gene variants and prenatal diagnosis of X-ALD pedigrees were summarized by descriptive statistics. Results:Twenty ABCD1 gene variants were identified in the 20 pedigrees. The variants in three probands that were not detected by next-generation sequencing were identified by PCR-Sanger sequencing. Among the mothers of the 20 probands, 17 carried ABCD1 variants and three did not. We performed 24 prenatal diagnoses on 20 pregnancies (24 fetuses) and identified eight fetuses with variants who were finally terminated. The 16 cases without variants were born alive. The validation results obtained after termination or delivery were consistent with those performed prenatally. Conclusions:No hotspot variants in ABCD1 gene are detected in these X-ALD patients and most variants are maternally inherited. PCR-Sanger sequencing is an effective method for detecting ABCD1 variants. Prenatal diagnosis for mothers who had a body with X-ALD could prevent another one from birth.
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Intestinal mucosal barrier is the first line of defense against exogenous substances. A complete mechanical barrier can separate the body from the contents of the intestines and prevent the translocation of bacteria and microorganisms in the intestines, playing an important role in maintaining the homeostasis of the human body. If the intestinal mechanical barrier function is damaged, it will cause the intestinal endotoxin and bacterial translocation, leading to systemic inflammatory response syndrome and multiple organ dysfunction diseases. The barrier function of intestinal mucosa is a key link in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, the maintenance of intestinal mucosal barrier function is of great value for the diagnosis and treatment of NAFLD. In this paper, the research progress in intestinal mechanical barrier function of NAFLD was reviewed, and the main factors maintaining intestinal permeability of NAFLD were introduced, such as apoptosis, autophagy, apical junctional complex, cytoskeleton, main signal pathway, to provide reference for the diagnosis and treatment of NAFLD.
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Objective:To observe the effect of abdominal mechanical stimulation on rats with irritable bowel syndrome-Diarrehea (IBS-D), and to explore the possible mechanism of abdominal massage mechanical stimulation to improve IBS-D.Method:60 newborn Wistar rats were randomly divided into blank group, model group and abdominal massage group, 20 rats for each group. The IBS-D rat model was established by separating the mother rats and newborn rats. In the abdominal massage group, the IBS-D rats were treated with abdominal rubbing once a day for 14 days. In the model group, the IBS-D rats were only bound to the experimental platform once a day for 5 min for 14 days. The rats in blank group were not made model and with no intervention. The intestinal motility and visceral sensitivity of rats were measured by the time of glass bulb expulsion and the abdominal lift volume threshold. The pathological changes of rat colon tissue were observed by hematoxylin-eosin staining. The changes of mast cells in colon tissue were observed by toluidine blue staining. The ultramicrostructure of intestinal glial cells was observed by transmission electron microscope. The content of proinflammatory factors IL-6 and IL-1β in rat plasma was determined by ELISA.Results:Compared with the model group, mechanical stimulation of the abdominal massage can significantly prolong the discharge time of the glass beads [(2.5±0.2) min vs (1.6±0.2) min], increase the abdominal lift volume threshold of rats [(0.5±0.1) ml vs (0.4±0.1) ml], improve the pathological state of the colon tissue, and reduce the number of mast cells [(2.64±0.22) per field vs (5.61±0.12) per field], reduce the number of mitochondria in the intestinal glial cells and increase the density of heterochromatin, and can also reduce the secretion of proinflammatory factors IL-6 [(189.4±4.7) pg/ml vs (224.8±8.6) pg/ml] and IL-1β [(178.4±7.1) pg/ml vs (191.4±8.4) pg/ml], and the differences were statistically significant (all P<0.05). Conclusions:Mechanical stimulation of abdominal massage can increase the visceral sensitivity of IBS-D rats, regulate intestinal glial cells and reduce the secretion of proinflammatory factors. The mechanism may be related to the intestinal-brain axis.
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Objective:To observe the structural and functional changes of each nucleus group in generalized anxiety disorder(GAD) rat models before and after the massage therapy, and to explore the central regulating mechanism of the massage therapy in GAD.Methods:60 Wistar male rats were randomly divided into blank group, model group and abdominal rubbing group, 20 rats for each group. GAD rat models were established by chronic emotional stress, and the models were evaluated by the elevated cross maze experiment. In the abdominal rubbing group, the GAD rats were treated with abdominal rubbing once a day for 10 min for 14 days. In the control group, the GAD rats were only bound to the experimental platform once a day for 10 min for 14 days. Horseradish peroxidase (HRP) retrograde tracking marker method was used to detect the changes of the structure of each nuclear cluster in the affective loop of the GAD rats in each group. The liquid-mass spectrometry quantitative analysis was used to determine the relative concentrations of N-acetyl aspartate (NAA), glutamic acid, choline and creatine in nuclear cluster of the GAD rats in each group.Results:Compared with the blank group, the HRP labeled cells in the rats of model group were less expressed and the activity of the emotional circuit in the brain was weak. The NAA/creatine ratio in the left hippocampal tissue of the rats in the model group was significantly increased than that of the blank group(0.94±0.08 vs 0.79±0.10, P<0.05), the glutamic acid/creatine ratio in the right hippocampal tissue was significantly decreased (0.95±0.10 vs 1.12±0.13, P<0.01), and the NAA/creatine andglutamic and acid/creatineratios in the left cortical tissue were all significantly decreased (1.04±0.05 vs 1.41±0.23, and 1.21±0.04 vs 1.57±0.11, all P<0.01). Compared with the model group, the hippocampal tissues of the GAD rats in the abdominal rubbing group had a large number of HRP aggregation and spread to the surrounding tissues, the NAA/creatine and glutamic acid/creatine ratios in the left hippocampal tissue of the abdominal rubbing group were significantly decreased (0.74±0.21 vs 0.94±0.09 and 0.92±0.20 vs 1.21±0.12, all P<0.01). The differences between the model group and the abdominal rubbing group in the ratio of glutamic acid/creatine in the right hippocampal tissue (1.01±0.23 vs 0.95±0.10), the ratio of NAA/creatine in the left cortical tissue (1.12±0.09 vs 1.04±0.05), and the ratio of glutamic acid/creatine in the left cortical tissue (1.22±0.12 vs 1.21±0.04) were not statistically significant ( P>0.05). Conclusions:Abdominal rubbing can effectively enhance the activity of affective loop and improve the relative concentration of neuron metabolites in hippocampal and cortical tissues in the affective loop, suggesting that the mechanism of GAD treatment by abdominal rubbing may be closely related to the structure and function of regulating affective loop.
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Objective To investigate the effect and molecular mechanism of the combination of mechanical strain stimulation and icariin (ICA) on inhibiting the differentiation of osteoclasts induced by fatigue load stimulation. Methods The mouse mononuclear macrophage cell line RAW264.7 was cultured in vitro, and the blank control group was α-MEM complete medium. In the fatigue load group, RAW264.7 cells were treated with 5000 μεmechanical stretch strain, and then cultured in an osteoclast culture medium that was an α-MEM complete medium containing 40 ng/ml macrophage colony-stimulating factor and 40 ng/ml osteoclast differentiation factor. In the mechanical stimulation + ICA group, RAW264.7 cells were treated as the same procedure in the fatigue load group, and then cultured in an α-MEM complete medium containing 1 ×10 -5 mol/L ICA simultaneously with a 1000 μεtensile strain on the substrate. The activity of tartrate-resistant acid phosphatase (TRAP) was detected using a TRAP assay kit. The mRNA expression of the osteoclast marker genes, i.e. TRAP, cathepsin K(CTSK) and matrix metalloproteinase 9 (MMP-9) was detected by real-time RT-PCR. The nuclear translocation of nuclear factor kappa B (NF-κB) was analyzed by Western Blot. Results Compared with the fatigue load group, the combination of mechanical stimulation (1000 με substrate stretching) and ICA (1×10-5 mol/L) could significantly inhibit the activity of TRAP in osteoclasts (P<0.01) and reduce osteoclastosis. Moreover, that combination not only could down-regulate the mRNA expression of TRAP, CTSK and MMP-9 and the differences were statistically significant (all P<0.01), but also could inhibit the formation of osteoclasts by inhibiting the phosphorylation of P65, P50 and IκB-α in NF-κB signaling pathway. Conclusions The coupling of mechanical stimulation and ICA can effectively inhibit the osteoclast differentiation and the bone resorption induced by fatigue load, and the mechanism may involve regulating NF-κB signaling pathway.
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<p><b>OBJECTIVE</b>To analyze the characteristics of germline mutations of adenomatous polyposis coli (APC) gene in pedigrees affected with familial adenomatous polyposis (FAP).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples from members of the 13 FAP pedigrees. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large fragment deletions of the APC gene. Subsequently, potential mutation was screened from all exons of the APC gene with PCR amplification and direct sequencing.</p><p><b>RESULTS</b>Germline mutations have been identified in 5 FAP pedigrees, which included c.3184_3187delCAAA, c.5432C>T, c.3925_3928delAAAA and c.3925_3929del AAAAG(in two pedigrees). Small deletional mutations were found primarily in the area of AAAAG tandem repeat sequences.</p><p><b>CONCLUSION</b>C.3925_3929 located in AAAAG tandem repeats is probably the hot spot for APC gene mutations, which are mostly deletional mutations, especially the 5 bp base deletion at codon 1309.</p>
Subject(s)
Adult , Female , Humans , Male , Adenomatous Polyposis Coli , Genetics , Adenomatous Polyposis Coli Protein , Genetics , Asian People , Genetics , Base Sequence , China , Molecular Sequence Data , Pedigree , Sequence DeletionABSTRACT
Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the most important targeted drugs for lung cancer patients carrying EGFR sensitive mutations.However,almost all patients that are effective to this treatment will eventually develop secondary resistance to EGFR-TKI.The most accepted mechanisms of resistance mainly include T790M mutation,MET amplification,PIK3CA mutation,down-regulation of PTEN expression and activation of Fas-transcription factor-κB.Recent years,many new drugs are developed to overcome this resistance.Although most of drugs are in the stages of cell or animal experiment,some new drugs get positive clinical results.
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@#Objective To explore the effect of comprehensive rehabilitation on patients with knee ankylosis and contracture of popliteal fossa after severe burn. Methods 35 patients with severe burn on lower limb (containing the around skin of popliteal fossa) accepted exercise therapy, hydrotherapy, occupation therapy (including pressure therapy), electrotherapy, etc. They were assessed with Functional Independence Measure (FIM), range of motion and muscle strength of knee before and after treatment. Results The scores of FIM, range of motion and muscle strength of knee improved after treatment (P<0.01). Conclusion Comprehensive rehabilitation can improve activities of daily living and function of knee after severe burn.
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Objective To explore the effects of gait training with an alternative gait orthosis (AGO) on the neurogenic bladders of patients with spinal cord injury (SCI). Method Twelve patients with complete SCI at the thoracic and lumbar level were trained for 8 weeks on motor and bladder function. After that, specific gait training with an AGO was given for another 8 weeks. American Spinal Injury Association ( ASIA ) sensation and motor function assessments were done before and after the gait training with the AGO, and bladder capacity, residual urine and urine flow rates were also assessed. Results Compared with pre-treatment there was no significant difference in average ASIA senzsation and motor scores after training, but the maximum rate of urine flow, average urine volume and single urination had significantly increased and residual urine volume had significantly decreased. Conclusions Therapeutic gait training with an AGO can improve bladder function after SCI.
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@#Objective To observe the effect of reciprocating gait orthosis on walking ability and activities of daily living (ADL) of patients with C6～T6 spinal cord injury (SCI).Methods 20 cases with C6～T6 SCI and according with type A and type B of ASIA standard received rehabilitation therapy, including training of muscle power, cardiopulmonary function, transferring mobility, ADL, bladder function, etc., before assembling the reciprocating gait orthosis, and additional gait training after fixing orthosis. The timed walking function assessment (6-min walking test and timed 10 meters walking test), gait analysis, Modified Barthel Index (MBI) and Functional Independence Measure (FMI) were used to assess pre- and post-training.Results The ADL ability of all cases improved obviously after equipping reciprocating ambulation orthosis, the walking ability also improved (P＜0.05). The mean timed 10 meters was 99.21±75.24 s, mean 6-min walk test was 41.71±29.38 m. From all patients, 14 cases achieved practicability walking ability, 6 cases achieved domestic walking ability.Conclusion The reciprocating gait orthosis combined with comprehensive rehabilitation therapy has effect on walking ability and ADL of patients with C6～T6 SCI.
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@#Objective To investigate the effect of continuous passive motion(CPM) and rehabilitation on flexion of the shoulder after intensive burn.Methods 36 patients with intensive burn on upper limb(including the skin around axilla fossa) were divided randomly into CPM group(n=19) and control group(n=17).The CPM group received both routine rehabilitation and continuous passive motion treatment,and the control group only underwent routine rehabilitation treatment.Their ranges of active or passive motion were assessed.Results There was a significant improvement both in the CPM group and the control group after treatment(P<0.01),but the CPM group improved more(P<0.05).Conclusion CPM can improve the efficacy of the routine rehabilitation on flexion of the shoulder after intensive burn.
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@#Objective To observe the effect of ankle-foot orthosis(AFO)on the activities of daily living(ADL)and walking ability of patients with low lumbar spinal cord injury.Methods29 cases with low lumbar spinal cord injury were trained by systematic rehabilitation.According to patients' condition,static AFO or dynamic AFO were assembled for them.All patients were evaluated with Modified Barthel Index(MBI)and Functional Independence Measure(FIM)before and after training,and the walking distances were also measured.ResultsAfter AFO dressed,the ADL scores of patients increased,especially walking ability increased significantly(P<0.05).Of 29 patients,26 cases had outdoor walking ability,3 cases had domestic walking ability.ConclusionSelecting different kinds of AFO according to condition of individual can help patients with low lumbar spinal cord injury to reconstruct their walking ability and improve ability of self-management.
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Objective To observe the therapeutic effects of systematic rehabilitation treatments on patients with upper limb dysfunction caused by fracture and soft tissue injury. Methods This study observed 45 cases of industrial injuries, with a involvement of 25 shoulder joints, 20 elbow and 23 wrist joints. All the patients were intervened with comprehensive rehabilitation treatments for 2.2?0.9 months, which included physiotherapy( joint mobilization, stretch technique, strength exercise, CPM, physical agent therapy and hydrotherapy), occupational therapy and orthosis. ROM, pain, the muscle strength of main muscle groups and ADL were assessed before and 2 months after treatment, respectively. Results There was significant difference with regard to ROM of the involved joints except for shoulder abduction after treatment when compared with those before the treatment (P
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@#Objective To observe the influence of the orthosis combined with functional training on patients' walking ability. Methods In different rehabilitation training stages, 36 patients, 11 cases of lumbar enlargement spinal cord injury (SCI), 25 cases of cerebrovascular accident (CVA) and head injury (HI), received strengthened training with ankle-food orthoses (AFO) for 6 weeks. And then, scores of ASIA, FMA and walking function in limited time (including 6 minute walking measures and 10 meters walking time measures) were evaluated respectively at admision, before and after applying AFO for 6 weeks. Results There was a significant difference in patients' walking function scores between before and after AFO training (P<0.01). However, SCI patients' ASIA scores have no significant changes after applying AFO for 6 weeks (P>0.05). In additional, HI patients' walking function scores after applying AFO for 6 weeks were more different from the scores at admision (P<0.01), and before AFO training (P<0.05). Conclusion AFO combined with functional training can obviously recover lumbar enlargement SCI and HI patients' walking ability.