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Objective:To analyze the relationship between preoperative deep vein thrombosis (DVT) and parameters of conventional coagulation tests (CCTs) and thromboelastography (TEG) in patients with acute trauma, and to establish a prediction model to screen out high-risk patients with preoperative DVT.Methods:The clinical data of patients with acute traumatic fracture admitted to the Emergency Intensive Care Unit of Shanghai Sixth People’s Hospital from January 2021 to June 2021 were retrospectively collected. According to whether preoperative DVT occurred, the patients were divided into the DVT group and non-DVT group. The differences of CCTs and TEG parameters at the same time were compared between the two groups. Logistic regression analysis was applied to identify independent risk factors for DVT after trauma. The receiver-operating characteristic curve analysis was employed to analyze the clinical value of those parameters to predict preoperative DVT.Results:Among 123 patients with acute traumatic fracture, 101 patients were treated with anticoagulation before operation, and 51 patients were diagnosed with DVT. There were significant differences in activated partial thromboplastin time, fibrinogen (Fib), D-Dimer, fibrinogen degradation products (FDPs), reaction time, clotting time, α angle, maximum amplitude (MA) and coagulation index between the DVT and non-DVT groups. D-Dimer and MA were independent risk factors for preoperative DVT in patients with traumatic fracture. Logistic regression equation was used to establish a prediction model: the predicting index = 0.101×D-Dimer +0.241×MA + (-18.190). The α angle (AUC=0.833, P<0.001), MA (AUC=0.904, P<0.001), coagulation index (AUC=0.914, P<0.001) of TEG versus Fib (AUC=0.684, P=0.001), D-Dimer (AUC=0.685, P<0.001) and FDPs (AUC=0.656, P=0.003) of CCTs had a higher diagnostic efficacy in developing DVT of lower extremity in patients with traumatic fracture, and of all the coagulation index was the best. However, the predictor of D-Dimer combined with MA had a better predictive value (AUC=0.926, P<0.001), and the best cut-off value was 0.32 with a sensitivity and specificity of 90.2% and 79.8%, respectively. Conclusions:Compared with CCTs, TEG has more advantages in predicting preoperative DVT in patients with traumatic fracture, and the predictor of D-Dimer combined with MA can screen out patients with high risk of DVT, which can be recommended for clinical application.
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Osteosarcoma is the most common primary solid bone malignancy. The main factor leading to recurrence and metastasis of osteosarcoma is resistance to chemotherapy drugs. Long non-coding RNAs can affect drug resistance in osteosarcoma by regulating epithelial-mesenchymal transition, cell autophagy, apoptosis, drug efflux, and cell cycle, suggesting that long non-coding RNAs may become new targets for drug resistance in osteosarcoma treatment.
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Objective:To investigate the distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia (AL), to analyze the risk factors for the occurrence of adverse events and to construct a nomogram model to predict the occurrence of adverse events.Methods:The clinical data of 313 AL patients with bloodstream infection who were admitted to the First Hospital of Jilin University from January 2018 to December 2020 were retrospectively analyzed, and the incidence, fatality and distribution characteristics of pathogenic bacteria after chemotherapy in AL patients were analyzed; the occurrence of adverse events (death or infectious shock) in patients with different clinicopathological characteristics were compared. Unconditional logistic binary regression model multifactor analysis was used to screen independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy; the nomogram model for predicting the occurrence of adverse events was developed by using R software; the Hosmer-Lemeshow test was used to verify the predictive effect of the model.Results:Of the 313 AL patients, the overall fatality rate was 4.2% (13/313), the all-cause fatality rate of bloodstream infection was 3.5% (11/313). Of the 313 cases, 254 cases (81.1%) were Gram-negative bacteria infection, mainly including 115 cases (45.3%) of Escherichia coli, 80 cases (31.5%) of Klebsiella pneumoniae, and 29 cases (11.4%) of Pseudomonas aeruginosa, and 10 cases (3.9%) died; 51 cases (16.3%) were Gram-positive cocci infection, mainly including 22 cases (43.1%) of Streptococcus spp., 20 cases (39.2%) of Staphylococcus spp., 7 cases (13.7%) of Enterococcus faecalis, and 0 case died; 8 cases (2.6%) were fungal infection, including 4 cases (1.3%) of Candida tropicalis, 2 cases (0.6%) of Candida subsmoothis, 1 case (0.3%) of Candida smooth, 1 case (0.3%) of new Cryptococcus, and 3 cases (37.5%) died. The differences in the occurrence rates of adverse events were statistically significant when comparing different treatment stage, risk stratification, timing of sensitive antibiotic use, total duration of fever, and glucocorticoid use in chemotherapy regimen, infecting bacteria carbapenem resistance, and leukemia remission (all P < 0.05). The results of logistic binary regression analysis showed that the use of glucocorticoid in chemotherapy regimen, the total duration of fever ≥7 d, the timing of sensitive antibiotic use ≥24 h, and carbapenem resistance of the infecting bacteria were independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy (all P < 0.05). A nomogram prediction model for the occurrence of adverse events in AL patients with bloodstream infection was established, and the nomogram model was calibrated and validated with good calibration and discrimination. Conclusions:The pathogenic bacteria of bloodstream infection after chemotherapy in AL patients is mainly Gram-negative bacteria, and the presence of glucocorticoid in chemotherapy regimen, long total duration of fever, poor timing of sensitive antibiotics, and infecting bacteria carbapenem resistance are risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy, and the nomogram prediction model based on these factors has a reliable predictive ability for the occurrence of adverse events.
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OBJECTIVE@#To explore the effect of leucine-rich α-2-glycoprotein (LRG1) derived from hepatocytes on activation of hepatic M1 Kupffer cells.@*METHODS@#A metabolic dysfunction-associated fatty liver disease (MAFLD) model was established in BALB/c mice by high-fat diet (HFD) feeding for 16 weeks. Oleic acid was used to induce steatosis in primary cultures of mouse hepatocytes. The mRNA and protein expressions of LRG1 in mouse liver tissues and hepatocytes were detected by real-time PCR and Western blotting. Primary hepatic macrophages were stimulated with the conditioned medium (CM) from steatotic hepatocyte along with LRG1 or transforming growth factor-β1 (TGF-β1), or both for 24 h, and the expression levels of inducible nitric oxide synthase (iNOS) was detected with Western botting, and the mRNA expressions of iNOS, chemokine ligand 1 (CXCL-1) and interleukin-1β (IL-1β) were measured by RT-PCR. The MAFLD mice were injected with LRG1 (n=6), TGF-β1 (n=6), or both (n=6) through the caudal vein, and the live tissues were collected for HE staining and immumohistochemical detection of F4/80 expression; the mRNA expressions of iNOS, CXCL-1 and IL-1β in liver tissues were detected using RT-PCR.@*RESULTS@#The mRNA and protein expression levels of LRG1 were significantly downregulated in the liver tissues of MAFLD mice and steatotic hepatocytes (P < 0.05). Treatment of the hepatic macrophages with CM from steatosis hepatocytes significantly enhanced the mRNA expression levels of iNOS, CXCL-1 and IL-1β, and these changes were significantly inhibited by the combined treatment with TGF-β1 and LRG1 (P < 0.05). In MAFLD mice, injections with either LRG1 or TGF-β1 alone reduced hepatic lipid deposition and intrahepatic macrophage infiltration, and these effects were significantly enhanced by their combined treatment, which also more strongly inhibited the mRNA expression levels of iNOS, CXCL-1 and IL-1β (P < 0.05).@*CONCLUSION@#LRG1 inhibits hepatic macrophage infiltration by enhancing TGF-β1 signaling to alleviate fatty liver inflammation in MAFLD mice.
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Animals , Mice , Transforming Growth Factor beta1 , Macrophage Activation , Signal Transduction , Non-alcoholic Fatty Liver Disease , Culture Media, Conditioned , GlycoproteinsABSTRACT
Objective@#To investigate the potential relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders (ASD), to provide a basis for the diagnosis and treatment of children with ASD.@*Methods@#A total of 40 ASD children who were treated or recovered in Xi an medical institutions and 16 typically developing (TD) children who were from several kindergatens in Xi an were invited for participation. Sensory characteristics were evaluated by the sensory processing and self regulation checklist, 3D structural brain images were obtained with TIWI, and gray matter volumes were analyzed by voxel based morphometry. Sensory characteristics and gray matter volumes were compared between groups and the relationship between sensory characteristics and different gray matter volumes were analyzed.@*Results@#The scores of auditory, visual, tactile, sensory processing ability and sensory under responsivity in the ASD group were lower than those in the TD group ( Z/t =-2.63, -2.57 , -3.11, -2.19, -3.83, P <0.05). Gray matter volumes in nine brain regions increased in the ASD group compared to the TD group, including the left and right posterior inferior lobe, right parahippocamal gyrus, left insula, left media frontal gyrus, left superion occipital gyrus, right superion occipital gyrus, right superion parietal lobe, and right posterion central gyrus ( t =3.53, 3.69 , 3.37, 3.86, 3.61, 3.37, 4.04, 3.38, 3.16, P <0.01). In the ASD group, the scores of visual, vestibular, proprioceptive, sensory processing ability, sensory seeking behavior and sensory over responsivity were negatively correlated with gray matter volumes of left superior occipital gyrus ( r =-0.36, -0.40, -0.39, -0.36, -0.40, -0.36), and the scores of visual, vestibular, and sensory over responsivity were negatively correlated with gray matter volumes of the right superior parietal lobule ( r =-0.36, -0.50, -0.42)( P <0.05).@*Conclusion@#The presence of paresthesia in children with ASD is associated with gray matter volumes of the left superior occipital gyrus and right superior parietal lobule.
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Objective:To observe the effects of sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the writhing reaction and score,the temperature and blood flow perfusion of moxibustion point area and uterus,the serum levels of arginine vasopressin(AVP),prostaglandin(PG)F2α,and thromboxane(TX)B2 in rats with primary dysmenorrhea(PD)due to cold-dampness stagnation,and to explore the possible mechanism of sparrow-pecking moxibustion in treating PD.Methods:Thirty-two healthy non-pregnant female Wistar rats were randomly divided into a normal group,a model group,an ibuprofen group,and a sparrow-pecking moxibustion group,with 8 rats in each group.Except for the normal group,the other three groups were subjected to modeling with cold water bath combined with estradiol benzoate and oxytocin injection.Rats in the sparrow-pecking moxibustion group were treated with sparrow-pecking moxibustion at Shenque(CV8)and Guanyuan(CV4)on the 8th day of modeling,30 min/time,once a day for 3 d;those in the ibuprofen group were treated with 0.8 mL ibuprofen solution(a specification of 125 mg in 10 mL)on the 8th day of modeling,once a day for 3 d;those in the normal group and the model group were given 0.8 mL normal saline,once a day for 3 d.On the 11th day,rats in each group were intraperitoneally injected with oxytocin(2 U/rat),and the writhing incubation period and writhing score in 20 min were observed;the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus in vivo were detected;the serum levels of AVP,PGF2α,and TXB2 were determined.Results:The writhing incubation period was significantly longer(P<0.01)and the writhing score was significantly lower(P<0.01)in the sparrow-pecking moxibustion group and the ibuprofen group than in the model group;compared with the ibuprofen group,the writhing incubation period was prolonged(P<0.01)and the writhing score was decreased(P<0.01)in the sparrow-pecking moxibustion group;compared with the normal group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly decreased,while the serum PGF2α,AVP,and TXB2 levels were significantly increased(P<0.01)in the model group;compared with the model group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased,and the serum levels of PGF2α,AVP,and TXB2 were significantly decreased in the ibuprofen group and the sparrow-pecking moxibustion group(P<0.05 or P<0.01);compared with the ibuprofen group,the temperature and the blood perfusion of Shenque(CV8),Guanyuan(CV4),and uterus were significantly increased(P<0.05),the serum AVP and TXB2 levels were significantly decreased(P<0.05),while the serum PGF2α level had no statistical difference in the sparrow-pecking moxibustion group(P>0.05).Conclusion:Sparrow-pecking moxibustion had a remarkable analgesic effect on the rats with PD due to cold-dampness stagnation,and the mechanism may be related to the increased temperature and blood perfusion of the moxibustion point area and uterus,as well as the decreased serum PGF2α,AVP,and TXB2 levels.
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Objective:To observe the effects of acupuncture at Houxi(SI3)and Huantiao(GB30)on the expression levels of nuclear factor kappa B(NF-κB),inducible nitric oxide synthase(iNOS),and nitric oxide(NO)of NF-κB inflammatory signaling pathway in L5 spinal nerve root of lumbar disc herniation(LDH)model rats and explore the mechanism of acupuncture in LDH treatment.Methods:Forty specific-pathogen-free healthy male Sprague-Dawley rats were randomly divided into a sham operation group,a model group,acupuncture group 1,and acupuncture group 2,with 10 rats in each group.The non-compression nucleus protrusion model was made by puncturing L4-L5 spinous process space and injecting autologous nucleus suspension.Acupuncture at bilateral Shenshu(BL23),Dachangshu(BL25),and Weizhong(BL40)was carried out in acupuncture group 1,and acupuncture at bilateral Houxi(SI3)and Huantiao(GB30)in acupuncture group 2.All rats were treated with balanced reinforcing and reducing needling manipulations,and the needles were retained for 30 min/time with one episode of needling manipulation every 10 min,once a day,14 times in total.The threshold value of paw withdrawal pain was measured by a thermal stimulation pain instrument;the serum NF-κB,iNOS,and NO levels were measured by enzyme-linked immunosorbent assay.The pathomorphological changes of spinal nerve roots were observed by hematoxylin-eosin(HE)staining;quantitative reverse transcription polymerase chain reaction was used to detect iNOS mRNA expression in spinal nerve roots;the NF-κB and iNOS protein expression in spinal nerve roots was detected by the immunofluorescence method.Results:Compared with the sham operation group,the threshold of paw withdrawal pain in the model group was decreased,and the expression levels of serum NF-κB,iNOS,and NO were increased;HE staining showed many degenerated and dissolved Schwann cells in spinal nerve roots with vacuolar changes;meanwhile,the expression levels of NF-κB and iNOS proteins,and the iNOS mRNA in spinal nerve roots were increased.Compared with the model group,the paw withdrawal pain thresholds in acupuncture group 1 and acupuncture group 2 were increased,and the increase in acupuncture group 2 was greater(P<0.05);the expression levels of serum NF-κB,iNOS,and NO in acupuncture group 1 and acupuncture group 2 were decreased,especially in acupuncture group 2(P<0.01);the vacuolar changes of spinal nerve roots,and the degeneration and lysis of Schwann cells in acupuncture group 1 and acupuncture group 2 were decreased,which were more obvious in acupuncture group 2;the NF-κB and iNOS protein expression and the iNOS mRNA expression levels in spinal nerve roots of acupuncture group 1 and acupuncture group 2 were decreased,especially in acupuncture group 2(P<0.01).Conclusion:Acupuncture at Houxi(SI3)and Huantiao(GB30)can improve the morphology of spinal nerve roots,inhibit the NF-κB and iNOS protein expression levels in spinal nerve roots and the serum NO level,and relieve the pain caused by inflammation of spinal nerve roots,which may be one of the mechanisms of acupuncture in LDH treatment.
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Objective:To investigate the effects and the possible mechanisms of Neiguan(PC6)and Gongsun(SP4)on the hypothalamic-pituitary-adrenal(HPA)axis in rats with functional dyspepsia(FD),thus to provide a theoretical basis for the clinical application of the Eight Confluent Points.Methods:Forty specific-pathogen-free Sprague-Dawley rats were divided into a blank group,a model group,an electroacupuncture(EA)group,and a Western medicine group by the random number table method,with 10 rats in each group.Rats in the blank group did not receive modeling or intervention.Rats in the other three groups were subjected to the FD with mood disorder model using the compound etiology modeling method.After the successful modeling,rats in the model group did not receive any interventions,rats in the Western medicine group received deanxit and mosaprid intervention,and those in the EA group received EA intervention on the ipsilateral Neiguan(PC6)and Gongsun(SP4)for 21 d.The sugar-water consumption rate was measured before the experiment and before and after interventions to assess the emotional status.The gastric emptying rate was measured after interventions to assess the gastrointestinal dynamics.The expression levels of hypothalamic corticotropin-releasing hormone(CRH),pituitary adrenocorticotropic hormone(ACTH),and adrenal corticosterone(CORT)were measured by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the sugar-water consumption rate and the gastric emptying rate were decreased(P<0.01),and the hypothalamic CRH,pituitary ACTH,and adrenal CORT expression levels were increased(P<0.01)in the model group.Compared with the model group,the sugar-water consumption rate and the gastric emptying rate were significantly increased(P<0.01),while the expression levels of hypothalamic CRH,pituitary ACTH,and adrenal CORT were significantly decreased(P<0.01)in the EA group and the Western medicine group.The differences between the EA group and the Western medicine group were not statistically significant(P>0.05).Conclusion:The Eight Confluent Points Neiguan(PC6)and Gongsun(SP4)can improve the mood and gastrointestinal dynamics in FD rats,which may be achieved by down-regulating the hypothalamic CRH,pituitary ACTH,and adrenal CORT,as well as by correcting the HPA axis hyperfunction.
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Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P＜0.05),while the expression of serum IL-10 was significantly decreased(P＜0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P＜0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P＜0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P＜0.05),and the serum IL-10 level was increased(P＜0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P＞0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.
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Objective:To observe the effect of large pushing Tianheshui manipulation intervention on the body temperature of young rabbits with endotoxin-induced fever and discuss its antipyretic mechanism.Methods:Thirty-two young rabbits meeting the standards were selected from 40 ordinary young male New Zealand rabbits after being adapted for 7 d,and randomly divided into a normal group,a model group,a large pushing Tianheshui group,and an ibuprofen group according to the random number table method,with 8 rabbits in each group.Rabbits in the model group,the large pushing Tianheshui group,and the ibuprofen group were subjected to preparing the endotoxin-induced fever model by intravenous lipopolysaccharide from the marginal ear vein.Rabbits in the large pushing Tianheshui group received Tuina(Chinese therapeutic massage)manipulation intervention 1.5 h and 2.5 h after modeling,respectively.Rabbits in the ibuprofen group were intragastrically given ibuprofen suspension 1.5 h after modeling.The dynamic changes in body temperature were observed for the young rabbits after fever modeling.Enzyme-linked immunosorbent assay was used to determine the content changes in positive mediators of hypothalamic body temperature,including prostaglandin(PG)E2 and cyclic adenosine monophosphate(cAMP),as well as negative mediators of hypothalamic body temperature,including arginine vasopressin(AVP)and α-melanocyte stimulating hormone(α-MSH).Results:The body temperature of the young rabbits in the model group was significantly higher than that in the normal group at 0.5-4.0 h,5.0 h,and 5.5 h after modeling(P＜0.01),showing two obvious fever peaks in the model group at 1.5 h and 3.0 h after modeling,respectively,with the highest peak at 1.5 h.Compared with the model group,body temperatures of the large pushing Tianheshui group and the ibuprofen group decreased significantly after 0.5 h of intervention(P＜0.05).Compared with the normal group,the contents of PGE2 and cAMP were significantly increased(P＜0.05),and the contents of AVP and α-MSH were significantly decreased(P＜0.01)in the hypothalamus of the model group.Compared with the model group,the contents of PGE2 and cAMP were significantly decreased(P＜0.01),and the levels of AVP and α-MSH were significantly increased(P＜0.01)in the hypothalamus in the large pushing Tianheshui group and the ibuprofen group.There were no significant differences in the PGE2,cAMP,AVP,and α-MSH contents in the hypothalamus between the ibuprofen group and the large pushing Tianheshui group(P＞0.05).Conclusion:Large pushing Tianheshui manipulation has a significant antipyretic effect on endotoxin-induced fever in young rabbits.The mechanism may be related to inhibiting the positive regulators(PGE2 and cAMP)and promoting the negative regulators(AVP and α-MSH)of hypothalamic control of body temperature.
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Objective:To investigate the effect and the mechanism of electroacupuncture(EA)on corpus striatum white matter injury in rats with focal cerebral ischemia(FCI).Methods:Forty-four specific-pathogen-free Sprague-Dawley rats were divided into a normal group(n=10),a sham-operation group(sham group,n=10),and a modeling group(n=24)using the random number table method.The normal group was a blank control.In the sham group,only the vessels and vagus nerve were isolated without embolization.The FCI rat model in the modeling group was replicated using the middle cerebral artery occlusion embolization method.The 20 successfully modeled rats were randomly divided into a model group and an EA group,with 10 rats in each group.Rats in the model group did not receive further treatment.Rats in the EA group received EA stimulation at Baihui(GV20)and the left Zusanli(ST36)24 h after the successful modeling,30 min each time,once a day for 14 d.On the 14th day of the experiment,rats in each group were scored for neurological deficits and then sacrificed,and brain tissues containing corpus striatum around the ischemic focus were paraffin-embedded from 5 rats in each group.Luxol fast blue(LFB)staining was used to detect damage changes in the white matter.The positive immunoreactive expression of myelin basic protein(MBP),myelin-associated growth inhibitor A(Nogo-A)and its receptor(NgR)in rat corpus striatum tissue was detected by immunohistochemistry staining,and then the protein expression of MBP,Nogo-A,and NgR in the corpus striatum tissue around the ischemic focus was determined by Western blotting.Results:Compared with the normal group and the sham group,the model group had a significantly higher neurological deficit score(P＜0.05)and fiber bundle injuries in the corpus striatum white matter,evidenced by a significantly lower mean optical density value of corpus striatum LFB staining(P＜0.05),a significantly lower MBP expression level(P＜0.05),and significantly higher Nogo-A and NgR protein expression levels(P＜0.05).Compared with the model group,the neurological deficit score was significantly lower(P＜0.05),the mean optical density value of LFB staining was significantly higher(P＜0.05),the MBP expression level was increased(P＜0.05),and the expression levels of Nogo-A and NgR proteins were decreased(P＜0.05)in the EA group.Conclusion:EA reduces the ischemia-induced corpus striatum white matter injury and improves neurological deficits.The mechanism may be related to the inhibition of Nogo-A/NgR activation.
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Objective: To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS). Methods: Forty male Sprague-Dawley rats were randomly divided into a normal group and a modeling group, with 20 rats in each group. Rats in the modeling group were subjected to preparing experimental UC models by drinking 4％ DSS for seven consecutive days. Two modeled rats and two normal rats were randomly selected for model identification. After the success of UC model was confirmed, the remaining 18 modeled rats were randomly divided into three groups, a model group, a model + herbal cake-partitioned moxibustion group, and a model + mild moxibustion group, with six rats in each group; the remaining normal rats were randomly divided into three groups, a normal group, a normal + herbal cake-partitioned moxibustion group, and a normal + mild moxibustion group, with six rats in each group. After 7 d of intervention with the herbal cake-partitioned moxibustion or the mild moxibustion, hematoxylin-eosin (HE) staining technique was used to observe the pathological changes of colon tissue under a light microscope; Western blotting and/or immunohistochemical techniques were used to detect the protein expression levels of Occludin, Claudin, junction adhesion molecular 1 (JAM1), mucin 2 (MUC2), and transforming growth factor beta1 (TGF-β1) in rat colon tissue. Results: Compared with the normal group, the colon tissue was severely damaged, the pathological score was significantly increased, and the protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 were significantly decreased in the model group (P<0.01); while there were no significant differences in the colonic histopathological score, protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 in the normal + herbal cake-partitioned moxibustion group and the normal + mild moxibustion group (P>0.05). Compared with the model group, the model + herbal cake-partitioned moxibustion group and the model + mild moxibustion group showed repaired colon tissue, ulcer healing, significantly reduced pathological score, and significantly increased protein expression levels of JAM1, MUC2, and TGF-β1 (P<0.05); the Occludin protein expression level in the colon tissue of the model + mild moxibustion group was increased (P<0.01). Conclusion: Neither herbal cake-partitioned moxibustion nor mild moxibustion influences the colonic histopathology and intestinal mucosal barrier-related protein expression in the normal rats; both herbal cake-partitioned moxibustion and mild moxibustion can up-regulate the protein expression levels of JAM1, MUC2, and TGF-β1 in the colon tissue of UC rats. Mild moxibustion can up-regulate Occludin protein expression. This may be a mechanism of moxibustion in reducing colonic mucosa inflammation in UC.
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OBJECTIVE@#To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD).@*METHODS@#Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter.@*RESULTS@#The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance.@*CONCLUSION@#Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.
Subject(s)
Humans , Autism Spectrum Disorder/genetics , Genomics , Heterozygote , Mosaicism , Exome SequencingABSTRACT
Objective: To observe the anti-inflammatory effect, as well as the effect on the expression of microtubule-associated protein light chain 3B (LC3B) and Beclin-1 of herbal cake-partitioned moxibustion in rats with experimental autoimmune thyroiditis (EAT). Methods: Female Sprague-Dawley rats were randomly divided into a normal group and a modeling group. The EAT rat model was prepared by a combination of antigen immunization plus iodine agent induction. After the model was prepared, rats in the modeling group were randomly and equally divided into a model group and a herbal cake-partitioned moxibustion group. In the herbal cake-partitioned moxibustion group, moxibustion was alternately applied to two groups of points [Dazhui (GV14)-Mingmen (GV4) and Tiantu (CV22)-Guanyuan (CV4)], and the treatment continued for 30 d. Rats in the normal and model groups were only fixed identically without intervention. Histopathological manifestations of thyroid glands were observed by hematoxylin-eosin staining; the concentrations of thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay; real-time fluorescence quantitative polymerase chain reaction and immunohistochemistry were used to detect the mRNA and protein expression of autophagy-related factors LC3B and Beclin-1 in thyroid tissue. Results: There were massive follicular destruction, lymphocytic infiltration, and interstitial fibrous tissue hyperplasia of the thyroid glands in the model group. Some follicles of the thyroid glands were destroyed with few lymphocyte infiltrations and fibrous tissue hyperplasia in the moxibustion group. Compared with the normal group, the concentrations of serum TPOAb, TGAb, IL-1β, IL-6, and TNF-α were increased in the model rats (P<0.05); the mRNA and protein expression levels of LC3B and Beclin-1 in thyroid tissue were reduced in the model group (P<0.05). Compared with the model group, the concentrations of serum TPOAb, TGAb, IL-1β, IL-6, and TNF-α were reduced in the herbal cake-partitioned moxibustion group (P<0.05); the mRNA and protein expression levels of LC3B and Beclin-1 in thyroid tissue were increased in the herbal cake-partitioned moxibustion group (P<0.05). The mRNA and protein expression of LC3B and Beclin-1 in thyroid tissue was negatively correlated with the serum levels of TPOAb and TGAb.Conclusion: Herbal cake-partitioned moxibustion reduces the inflammatory response in the thyroid glands of EAT rats and lowers the levels of serum TPOAb and TGAb. This may be related to the regulation of mRNA and protein expression of the autophagy-associated factors LC3B and Beclin-1 in rat thyroid tissue.
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Objective: To observe the effect of Tuina (Chinese therapeutic massage) on creatine kinase (CK), mitochondrial Ca2+ concentration, and ultrastructure of skeletal muscle in delayed onset muscle soreness (DOMS) model rats.Methods: A total of 130 healthy male Sprague-Dawley rats were randomly divided into a blank group, an exercise control group, a pre-exercise Tuina group, and a post-exercise Tuina group. According to the time points for sample collection, the exercise control group was divided into a 0 h exercise control group, a 24 h exercise control group, a 48 h exercise control group, and a 72 h exercise control group; the pre-exercise Tuina group was further divided into a 0 h pre-exercise Tuina group, a 24 h pre-exercise Tuina group, a 48 h pre-exercise Tuina group, and a 72 h pre-exercise Tuina group; and the post-exercise Tuina group was divided into a 0 h post-exercise Tuina group, a 24 h post-exercise Tuina group, a 48 h post-exercise Tuina group, and a 72 h post-exercise Tuina group. Rats in all groups except for the blank group received DOMS modeling. Professionals performed Nie-Pinching manipulation and finger Nian-Twisting manipulation on the lower limbs of the rats. The samples were collected at 0 h, 24 h, 48 h, or 72 h after exhaustive exercise for each pre-exercise Tuina group. The samples were collected at 0 h, 24 h, 48 h, or 72 h after Tuina for each post-exercise Tuina group. The changes in serum CK, skeletal muscle mitochondrial Ca2+ concentration, and Ca2+-adenosine triphosphatase (ATPase) were determined. The ultrastructure changes of skeletal muscles in each group were observed by a transmission electron microscope. Results: The electron microscope showed that compared with the exercise control group, the skeletal muscle structures of the pre-exercise Tuina group and the post-exercise Tuina group were significantly improved, and the overall performance of skeletal muscle in the pre-exercise Tuina group was more similar to that of the blank group. The level of serum CK in the pre-exercise Tuina group and the post-exercise Tuina group was significantly lower than that in the exercise control group (P<0.01). The Ca2+ concentration of skeletal muscle in the 24 h, 48 h, and 72 h pre-exercise Tuina groups was lower than that in the post-exercise Tuina group at the same time point (P<0.01). The Ca2+-ATPase concentration of skeletal muscle in the 24 h and 72 h pre-exercise Tuina groups was lower than that in the post-exercise Tuina group at the same time point (P<0.05).Conclusion: Tuina effectively prevents muscle damage caused by heavy exercise and long-term exercise, which may be related to the increase of skeletal muscle Ca2+-ATPase activity and mitochondrial Ca2+ transport.
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Objective: To investigate the mechanism of moxibustion in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), by observing the effects of moxibustion at Tianshu (ST25) and Shangjuxu (ST37) on microRNA-133b (miRNA-133b), pituitary homeobox family factor 3 (Pitx3)/tyrosine hydroxylase (TH), and neurotransmitters in the brain tissue of IBS-D rats. Methods: Healthy Sprague-Dawley rats were randomly divided into a normal group, a model group, a moxibustion group, and a Western medicine group, with 12 rats in each group. Except for the normal group, the IBS-D rat model was established by mother-offspring separation and acetic acid enema combined with restraint stress stimulation in all the other groups. No intervention was performed in the normal and model groups. Mild moxibustion was applied to both Tianshu (ST25) and Shangjuxu (ST37) in the moxibustion group. Rifaximin was given by gavage in the Western medicine group. The physical status of rats in each group was observed at different periods. After the intervention, hematoxylin- eosin staining was performed to observe the histopathological morphology of rat colon; enzyme-linked immunosorbent assay was used to measure the levels of dopamine (DA), noradrenaline (NE), and 5-hydroxytryptamine (5-HT) in plasma, colon, and midbrain tissue of rats; the relative expression levels of miRNA-133b, Pitx3 mRNA, and TH mRNA in the midbrain tissue were measured by real-time fluorescence quantitative polymerase chain reaction, and the relative expression levels of Pitx3 and TH proteins in the midbrain tissue were measured by Western blotting and immunofluorescence. Results: The body weights of rats among groups and at different time points were statistically different (P<0.01). The body weight of the normal group was higher than that of the other groups over time (P<0.01). After modeling, the minimum volume threshold of abdominal withdrawal reflex (AWR) was significantly lower (P<0.01) and the loose stool rate was significantly higher (P<0.01) in the model, moxibustion, and Western medicine groups compared with the normal group; the miRNA-133b expression in the midbrain tissue was significantly lower (P<0.01), the expression levels of Pitx3 and TH in the midbrain tissue were significantly higher (P<0.01), and the levels of DA, NE, and 5-HT in plasma, colon and midbrain tissue were significantly higher (P<0.01). After the intervention, the minimum volume threshold of AWR was significantly higher (P<0.01), the loose stool rate was significantly lower (P<0.01), the miRNA-133b expression was significantly increased (P<0.01 or P<0.05) and the expression levels of Pitx3 and TH were significantly decreased (P<0.01) in the midbrain tissue, the levels of DA, NE, and 5-HT in plasma, colon, and midbrain tissue were significantly reduced (P<0.01) in the moxibustion and Western medicine groups compared with the model group; the levels of 5-HT in the colon and midbrain tissue of the moxibustion group were significantly lower than those in the Western medicine group (P<0.05), and there was no statistical difference compared with the remaining groups (P>0.05). Linear correlation analysis showed that miRNA-133b was negatively correlated with Pitx3 (r<0, P<0.01); Pitx3 with TH, TH with DA, and NE with 5-HT were positively correlated (r>0, P<0.01).Conclusion: Moxibustion at Tianshu (ST25) and Shangjuxu (ST37) improves diarrhea symptoms and visceral hypersensitivity in IBS-D rats. The mechanism may be related to up-regulating miRNA-133b, inhibiting Pitx3/TH, and reducing neurotransmitter expression levels in the midbrain tissue.
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Objective: To observe the effect of Mo-Rubbing abdomen manipulation on glucose metabolism and inflammatory factors in rats with type 2 diabetes mellitus (T2DM). Methods: Sixty Sprague-Dawley rats were randomly divided into a normal group (n=10) and a group for modeling (n=50) using the random number table method. Rats in the group for modeling were induced to form T2DM models by a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. Thirty successfully modeled rats were randomly divided into a model group, a Mo-Rubbing abdomen group, and a metformin group, with 10 rats in each group. Rats in the normal group and the model group received no intervention, those in the Mo-Rubbing abdomen group received Mo-Rubbing abdomen manipulation, and those in the metformin group received metformin by gavage. After 8-week intervention, fasting insulin (FINS), fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR) and area under the curve at the oral glucose tolerance test (AUC-OGTT), as well as serum inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were detected, and the morphological changes of the pancreas were also observed. Results: After the 8-week intervention, the levels of FINS, FPG, HOMA-IR, and AUC-OGTT of rats in the Mo-Rubbing abdomen group were significantly lower than those in the model group (P<0.05); the pancreatic injury degree in the Mo-Rubbing abdomen group and the metformin group was lower than that in the model group. Compared with the model group, the serum IL-1β, IL-6, and TNF-α levels of rats in the Mo-Rubbing abdomen group were significantly decreased (P<0.05), and the serum IL-1β and TNF-α levels of the metformin group showed a downward trend; the serum IL-6 and TNF-α levels in the Mo-Rubbing abdomen group were significantly lower than those in the metformin group (P<0.01). There was a significant positive correlation between FPG with IL-1β, IL-6, and TNF-α in the T2DM rats (P<0.01). Conclusion: Mo-Rubbing abdomen manipulation reduces the inflammatory response and improves the morphological changes of the pancreas in T2DM rats, thereby achieving the effect of lowering blood glucose.
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Objective: To observe the effect of the acupuncture plus medication on the expression of silent information regulator of transcription 1 (SIRT1) and transcription factor forkhead box protein O3a (FOXO3a) in the hippocampus, the malondialdehyde (MDA) content, and the superoxide dismutase (SOD) activity of rats with Alzheimer disease (AD), and to explore the possible mechanism of combining acupuncture and medication in improving AD-related neurological symptoms. Methods: Sixty male Sprague-Dawley rats were divided into a normal group, a model group, an electroacupuncture (EA) group, a drug group, and an acupuncture-medication combined group by the random number table method, with 12 rats in each group. The model was established by micro-injection of streptozotocin into the bilateral lateral ventricles. After successful modeling, rats in the EA group received EA at Zusanli (ST36) and Dazhui (GV14), those in the drug group received intragastric administration of resveratrol at a dose of 44 mg/(kg·bw), and those in the acupuncture- medication combined group received the combined intervention of EA and resveratrol. Rats in each group received intervention once a day for 4 consecutive weeks. Morris water maze was used to detect the rat behavioral changes. Nissl staining method was used to observe the cell morphology and changes in the number of rat hippocampal neurons. Western blotting and immunohistochemical staining methods were used to observe the expression changes of SIRT1 and FOXO3a. The thiobarbituric acid method was used to detect the MDA content. SOD activity was determined by the hydroxylamine method. Results: Compared with the normal group, the escape latency was significantly prolonged (P<0.05); the percentage of stay in the target quadrant was reduced (P<0.05), the hippocampal neuronal cells were shrunken, nucleoli were unclear, and cell number was reduced (P<0.05); the SIRT1 expression and SIRT1 positive cell number were decreased, while the FOXO3a expression and FOXO3a positive cell number were increased significantly (P<0.05); the MDA content was increased significantly, and the SOD activity was decreased significantly (P<0.05) in the model group. Compared with the model group, the escape latency was shortened (P<0.05); the percentage of stay in the target quadrant was increased (P<0.05); the shape and number of hippocampal neurons tended to be normal (P<0.05); the SIRT1 protein expression and the SIRT1 positive cell numbers were increased, the FOXO3a protein expression and the FOXO3a positive cell number were decreased (P<0.05); the MDA content was significantly decreased, and the SOD activity was significantly increased (P<0.05) in the EA group, the drug group, and the acupuncture-medication combined group. The changes in the acupuncture-medication combined group were more obvious (P<0.05). Conclusion: Both EA and resveratrol improve the learning and memory ability of AD rats by regulating the expression of SIRT1 and FOXO3a and improving the levels of MDA and SOD in the hippocampus and protect the hippocampal neurons, while the combined use of EA and medication is more effective than EA or resveratrol alone, suggesting that this combined treatment is more effective in AD treatment.
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Objective: To explore the mechanism of An-Pressing manipulation in relieving energy crisis in chronic myofascial trigger points (MTrPs) by observing the effects of An-Pressing manipulation on adenosine triphosphate (ATP), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway and mitochondrial ultrastructure of skeletal muscle cells in MTrPs rats. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into a blank group, a model group, a lidocaine group, and an An-Pressing manipulation group, with 12 rats in each group. The model group, lidocaine group and An-Pressing manipulation group were used to replicate the MTrPs rat model by blunt shock and centrifugal motion method. After modeling, the An-Pressing manipulation group was subjected to 7 times An-Pressing manipulation, once every other day; the lidocaine group was treated with 3 times of injection of lidocaine at the MTrPs, once every 6 d. The blank group and the model group were fed normally without intervention. After the intervention, local muscle tissue was taken to detect the content of ATP and the expression of AMPK, phosphorylated AMPK (phospho-AMPK), PGC-1α, and glucose transporter 4 (GluT4), and the ultrastructure of mitochondria was observed under an electron microscope. Results: Compared with the blank group, the ATP content in the model group was decreased (P<0.05), the protein expression levels of phospho-AMPK, PGC-1α, and GluT4 and the ratio of phospho-AMPK to AMPK were decreased (P<0.05); under the electron microscope, the number of mitochondria decreased, and they were deformed, small in volume, and had deformed cristae. Compared with the model group, the ATP contents in the An-Pressing manipulation group and the lidocaine group were increased (P<0.05), and the protein expression levels of phospho-AMPK, PGC-1α, and GluT4 and the ratio of phospho-AMPK to AMPK were increased (P<0.05); under the electron microscope, the number of mitochondria increased, the shape and size of the mitochondria were basically normal, and the cristae could be seen. Compared with the lidocaine group, phospho-AMPK and the ratio of phospho-AMPK to AMPK in the An-Pressing manipulation group were increased (P<0.05); under the electron microscope, the numbers of mitochondria were similar, and the shape and size of the mitochondria were basically normal without swelling, and the cristae could be observed. Conclusion: An-Pressing manipulation can increase the ATP content in MTrPs tissue, improve the expression levels of PGC-1α and GluT4 proteins and the ratio of phospho-AMPK to AMPK; its mechanism may relate to the activation of AMPK/PGC-1α signaling pathway to promote the repair of mitochondrial damages.
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Objective: To observe the effect of moxibustion on the expression of N-methyl-D-aspartic acid (NMDA) receptor subtype 2B (NR2B) in the hippocampus of rheumatoid arthritis (RA) rats, and to explore the analgesic mechanisms of moxibustion in RA treatment. Methods: Sixty male Sprague-Dawley rats were randomly divided into a normal group, a model group, a moxibustion group, a moxibustion + NMDA receptor antagonist (AP-5) group, and a moxibustion + NMDA receptor agonist (NMDA) group, with 12 rats in each group. Except for the normal group, rats in the other four groups were treated with complete Freund's adjuvant in a windy, cold, and damp environment to replicate RA models. Rats in the moxibustion group received suspended moxibustion with moxa sticks at Shenshu (BL23) and Zusanli (ST36), and the two points were used alternately. After intraperitoneal injection of AP-5 or NMDA, rats in the moxibustion + AP-5 group and the moxibustion + NMDA group received the same moxibustion intervention as in the moxibustion group, once a day for 15 d. The thermal withdrawal latency (TWL) of rats in each group was detected before and after modeling and after the 15-day intervention. After the 15-day intervention, hematoxylin-eosin staining was performed to observe the pathological changes in knee joints. The real-time fluorescence quantitative polymerase chain reaction method was used to detect the mRNA expression of NR2B in the hippocampus; Western blotting assay was used to detect the protein and the phosphorylated protein expression of hippocampal NR2B. Results: The synovial tissue was proliferated, the synovial lining was significantly thickened, the pannus was formed, and the cartilage and bone tissues were significantly damaged in the model group. After intervention, the pathological morphology of the knee joints in the moxibustion group, the moxibustion + AP-5 group, and the moxibustion + NMDA group was significantly improved, and the improvement in the moxibustion + AP-5 group was more notable than that in the moxibustion + NMDA group. Compared with the normal group, the TWL was significantly decreased (P<0.01), and the mRNA, protein, and phosphorylated protein expression levels of hippocampal NR2B were significantly increased in the model group (P<0.01). Compared with the model group, the TWL of each intervention group was significantly increased (P<0.01 or P<0.05), and the mRNA, protein, and phosphorylated protein expression levels of hippocampal NR2B were significantly decreased (P<0.01). Compared with the moxibustion group, the TWL was significantly increased (P<0.01), and the mRNA, protein, and phosphorylated protein expression levels of hippocampal NR2B were significantly decreased in the moxibustion + AP-5 group (P<0.01); the TWL was significantly decreased (P<0.01), and the mRNA, protein, and phosphorylated protein expression levels of hippocampal NR2B were significantly increased in the moxibustion + NMDA group (P<0.01). Conclusion: Moxibustion reduces hyperalgesia in RA inflammatory rats. The analgesic effect may be related to the decrease in the expression and phosphorylation levels of NR2B in the hippocampus.