Cajal initially identified interstitial cells of Cajal (ICC).In recent decades the researches on ICC were rapid.It is known to all that ICC contribute to several important functions in the gastrointestinal tract including:generation of electrical slow wave activity,coordination of pacemaker activity and active propagation of slow waves,transduction of motor neural inputs from the enteric nervous system,and mechanosensation to stretch of gastrointestinal muscles.The changes of morphology,distribution,number,phenotypic in ICC might affect on the gastrointestinal function,and might lead to gastrointestinal disease.Expression of c-kit has an important role in the ICC.Regulation of SCF/c-kit signaling system can lead to changes in morphology of ICC.In the gastrointestinal tract,motilin receptor expression in the ICC.The promotion of motilin receptor agonist to intestinal tract were mediated by ICC.ICC can be isolated and subcultured.

Objective To investigate the efficacy and safety of tranexamic acid on bleeding in rheumatoid arthritis (RA) patients undergoing total hip arthroplasty (THA). Methods A retrospective study was performed in 197 RA patients (Steinbrock?er III-IV) following primary unilateral THA from June 2012 to June 2014. The patients were divided to three groups based on the regimen of tranexamic acid:68 patients received a single intravenous dosage of 15 mg/kg tranexamic acid 20 min prior to opera?tion (single dose group);74 patients received an intravenous dosage of 15 mg/kg preoperatively and a second dosage of 10 mg/kg 3 hours postoperatively (repeated dose group);the other 55 patients didn't receive tranexamic acid (control group). The primary out?comes were total blood loss, transfusion rate, the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE). The sec?ondary outcomes were postoperative drainage, hemoglobin (Hb) drop on third day postoperatively and other wound related compli?cations. Results There was less total blood loss (816.80 ± 245.09 ml vs 975.15 ± 216.33 ml vs 1 295.68 ± 263.85 ml), drainage (221.60 ± 70.05 ml vs 337.20 ± 113.10 ml vs 479.74 ± 120.66 ml), transfusion requirement (5.41%vs 10.29%vs 25.45%) and Hb drop (2.71±0.74 g/dl vs 3.18±0.62 g/dl vs 3.83±0.70 g/dl) in experimental group when compared with control group. And the effect was better in repeated dose group, with less total blood loss (816.80 ± 245.09 ml), less transfusion requirement (5.41%) and less postoperative drainage (221.60±70.05 ml). No episode of DVT or PE occurred in either group. There were 8 wound complications in single dose group, 6 in repeated group, and 8 in control group, and there were no statistically difference. Conclusion Intrave?nous administration of tranexamic acid was effective and safe on decreasing blood loss and transfusion requirement in RA patients following THA. Compared with a single dosage of tranexamic acid preoperatively, a second dosage of tranexamic acid 3 hours post?operatively was recommended.

Osteonecrosis of the femoral head (ONFH) is caused by the blockage of the blood supply of the femoral head due to by a variety of reasons, resulting in the death of the bone in the femoral head, which is characterized by osteonecrosis occurdead bone resorption-new bone formation. And total hip arthroplasty (THA) is the final choice for the vast majority of these patients. Though treating hard, it is necessary to choose an appropriate head-preserving treatment in the early stage to delay the time of THA.Methods to treat femoral head necrosis varies, however, it is still hard to have a uniform standard until now. Thus, this paper discusses the epidemiological characteristics, related risk factors, pathology, stage, current head-preserving methods and prognostic factors of femoral head necrosis, so as to further enhance clinicians' understanding of osteonecrosis of the femoral head and provide reference to choose more appropriate head-preserving methods for those patients. As demonstrated in literatures, in China, the incidence of non-traumatic ONFH in males is significantly higher than that in females, and it is more common in northern residents and urban residents. In addition, glucocorticoid intake, hyperlipidemia, heavy smoking and alcohol abuse tend to increase the risk of ONFH; Histologically, osteonecrosis and repair of the femoral head occurred after blood supply was blocked; In terms of pathological staging, Ficat staging is the most commonly used and most directly classification method; core decompression, non-vascularized bone grafting, vascularized bone grafting and osteotomy are still the mainstream surgical methods at present. Patient's age, etiology, stage, etc are important factors affecting the prognosis of ONFH. Therefore, surgeons can choose the most appropriate treatment for the patients according to their specific conditions and prognostic factors.

Objective To establish the young rabbit models with gastroesophageal reflux (GER) and observe the effect of erythromycin in different parts of muscle segment (fundus ventriculi and lower esophageal),so as to investigate the variation after destroying the interstitial cells of Cajal (ICC).Methods Forty young rabbits of 8 weeks old were randomly divided into control group(n =20) and experimental group(n =20).In the experimental group,the fun dus ventriculus was partly ligated combined with helicobacter restriction at a level near the pylorus to establish GER young rabbit models.In the control group,the fundus ventriculi and pylorus were dissociated then the abdomen was closed.Four weeks later,10 rabbits from the experimental group and 10 rabbits from the control group were taken,2 lower esophageal segments and 2 fundus ventriculi muscle segments were split in each animal,and the ICC were destroyed at 1 lower esophageal segment and 1 fundus ventriculi muscle segment.The amplitude and frequency of lower esophageal and fundus ventriculi muscle segments were measured by using electrophysiology in vitro.Results (1) After 4 weeks of operation,the GER young rabbit models were successfully established.The data were detected by esophageal pH monitoring,general morphology observation and HE stain.Immunohistochemical staining of specific receptors protein c-kit on ICC showed that the ICC in the experimental group was reduced remarkably,and the morphological characteristics changed.(2) In the control group,the frequency and amplitude of lower esophageal muscle segments were (2.60 ± 0.70) times/min and (3.03 ± 0.59) g,the frequency and amplitude of fundus ventriculi muscle segments were (3.50 ± 0.97) times/min and (5.33 ± 1.09) g;in the experimental group,the frequency and amplitude of lower esophageal muscle segments were reduced to (0.29 ± 0.49)times/min and (0.61 ±0.43) g;the frequency of fundus ventriculi muscle segmens in the experimental group turned to (0.43 ± 0.54) times/min and the amplitude was (1.13 ± 0.41) g,and there were statistically differences compared with those of the control group (t =9.86,8.15,8.29,12.55,all P ＜ 0.05).(3) The influence of erythromycin in the lower esophageal and fundus ventriculi muscle segments:the amplitude after injecting erythromycin of lower esophageal muscle segments in the experimental group was (1.16 ± 0.83) g,the amplitude was significantly different (t =2.35,P ＜ 0.05),while the frequency had no relevance (P ＞0.05);the amplitude of fundus ventriculi muscle segments in the experimental group was (4.20 ± 1.14) g,and the difference was statistically significant(t =4.76,P ＜ 0.05),and there was no statistically more differences in the frequency (P ＞ 0.05).In the control group,the frequency and amplitude of lower esophageal muscle segments were (4.50 ±0.84)times/min and (5.13 ± 0.94) g,the frequency and amplitude of fundus ventriculi muscle segments increased to(5.40 ± 1.43) times/min and(7.50 ± 1.28) g,and the differences were statistically significant (t =3.79,5.78,3.06,6.45,all P ＜ 0.05).(4) The contraction activity of muscle segments after adding the erythromycin was prevented in the lower esophageal muscle segments or fundus ventriculi muscle segmens.Conclusions ICC plays an important role in the animal models of GER;erythromycin promotes the motility of the muscle segments in GER young rabbit models;in the sick models,erythromycin accelerates the gastrointestinal motility via ICC on muscle segments.

Objective To investigate the relationship between cow's milk protein allergy(CMPA)and gastroesophageal reflux disease(GERD)and the prognosis of GERD combined with CMPA.Methods Fifty patients(24 boys and 26 girls)with GERD were enrolled in this study from January 2015 to June 2016 at Department of Pediatrics,Tangdu Hospital of the Fourth Military Medical University.All children were treated with serum milk protein soluble IgE(sIgE)and milk protein avoidance test,and those with positive results of children's milk protein by provocation test and those with milk serum protein sIgE negative by milk protein provocation tests were diagnosed as CMPA children with GERD according to the CMPA diagnostic criteria and received diet therapy for 1 month and then their blood eosinophil ratio and 24-hour esophageal pH were monitored.Results Twenty-three cases(46％)of 50 children with GERD were diagnosed as CMPA.There was significant difference in clinical symptoms between GERD group and GERD combined with CMPA group(x2=22.78,P<0.05),but there existed cross-symptoms among individual patients,so clinical accurate diagnosis turned out to be difficult.There was no significant difference in family history of allergy between GERD group and GERD combined with CMPA group(x2=3.19,P>0.05).For children with GERD combined with CMPA,the patients received dietary treatment for 1 month.There was significant improvement in vomiting,runny nose/wheezing/cough and diarrhea(P<0.05).However,because the treatment of eczema was long and it could relapse easily,there was no significant change after 1 month of therapy(P>0.05).The proportions of blood eosinophils were decreased after treatment compared with those before treatment [(2.7±1.8)％vs.(8.2±2.7)％,t=10.006,P<0.01].The results of 5 children's 24-hour esophageal pH monitoring showed that the reflux index and the number of acid GERD episodes were lower than before,and the difference was all statistically significant before and after(all P<0.05).Conclusions The occurrence of GERD in infants is partly related to CMPA,and the treatment of CMPA can relieve the clinical symptoms of GERD.

Objective:To investigate the expression of connexin-43 (Cx43) in steroid-induced osteonecrosis of femoral head and osteoblasts in rats and its regulation mechanism.Methods:The model of steroid-induced osteonecrosis of femoral head (SIONFH) of rat was established. Micro-CT and HE staining were used to observe the degree of bone trabecular destruction and the incidence of empty lacunae. The expression levels of Cx43 and PI3K/Akt signaling pathway related molecules and osteoblast-related proteins in model group and control group were detected by RT-PCT and Western blot. The osteoblast (OB) of rats was further isolated and cultured in vitro. Under treatment of dexamethasone (Dex), Cx43 expression in OB cells was detected by Western blot and immunofluorescence. Western blot was used to detect the effect of glucocorticoid (GC) on the expression of related molecules of PI3K/Akt/β-catenin signaling pathway. Akt activator (SC79) and PI3K inhibitor (LY294002) were used to study the molecular mechanism of Dex regulation on Cx43 expression in OB cells. The regulatory relationship between β-catenin and Cx43 was investigated by immunoprecipitation and small interfere RNA (siRNA) technology.Results:The model of SIONFH in rats was successfully established, which proved that Cx43 expression level in the SIONFH model group was significantly lower than that in the control group, and the expression level of Cx43 was positively correlated with the expression of PI3K/Akt signaling pathway related molecules and osteoblast-related proteins Runx2, ALP and Collagen I Type (COL). In addition, in vitro culture of isolated rat OB cells, the expression of Cx43, p-PI3K, P-Akt and β-catenin in OB cells decreased gradually as the Dex action time went on. Moreover, SC79 pretreatment could significantly reverse the inhibitory effect of GCs on Cx43 expression, while LY294002 could significantly enhance the inhibitory effect of GCs on Cx43. In addition, the immunoprecipitation results showed that β-catenin expression was closely related to Cx43 expression, and further studies showed that β-catenin-siRNA could significantly down-regulate the expression of Cx43.Conclusion:Under the action of GC, the expression level of Cx43 in bone tissue and OB cells decreased significantly, and the possible mechanism was that GCs inhibited the expression of Cx43 by inhibiting the PI3K/Akt/β-catenin signaling pathway, which laid a new theoretical foundation for the further study of the role of Cx43 in the pathogenesis of steroid-induced femoral head necrosis.

Effective bone repair and regeneration is crucial for treating skeletal tissue defects, including osteonecrosis, nonunion fractures, osteoporosis, and various other bone deficiencies. Exosomes, as cellular secretory vesicles, are pivotal in mediating intercellular communication through their cargo of proteins, lipids, and nucleic acids. Mesenchymal stem cell-derived exosomes, in particular, have emerged as promising agents in bone repair and regeneration, showing potential for practical application and clinical translation. Nonetheless, their functional capacity and therapeutic efficacy require enhancement. This review delineates exosome optimization strategies aimed at augmenting secretion and functionality, alongside the incorporation of exosome-functionalized biomaterials for bone healing. Evidence indicates that physical stimulation, molecular interventions, and small-molecule or biomaterial stimuli are effective in increasing exosome output. Moreover, engineering exosomes and their parental cells can further potentiate their therapeutic function. The amalgamation of exosomes with biomaterials represents a burgeoning approach in bone tissue engineering, offering novel therapeutic avenues. This comprehensive analysis aims to guide future applications and the clinical adoption of exosomes in bone tissue restoration.

Objective To study the feasibility and value of magnetic resonance diffusion tensor imaging (DTI) to monitor non?arteritic anterior ischemic optic neuropathy (NAION). Methods Thirty eight NAION patients (56 eyes) were divided into acute period in 17 eyes, progressive period in 16 eyes and chronic period in 23 eyes at the base of onset time. According to matching principle, 56 eyes in 38 normal controls (NCs) were enrolled. All the patients and NCs underwent MR and DTI scan. The raw data were processed by two experienced radiologists, mean diffusivity (MD), axial diffusivities (λ//), radial diffusivities (λ┴), fractional anisotropy (FA) and Length value were got. The independent sample t test was used for the parameter values between the NAION group and the NCs group. A single factor variance analysis was used to compare the parameters among different stages of NAION group. Results Compared to the NCs group, the values of FA and Length in NAION group were reduced [0.20±0.11 vs 0.31±0.12, (5.85±0.92) vs (65.11± 6.89) mm], and the differences were statistically significant (t=-4.28,-5.25;P<0.05). The values of MD andλ┴were increased [(0.16±0.04)×10-3 vs (0.10±0.04)×10-3 mm2/s, (0.16±0.05)×10-3 vs (0.09±0.03)×10-3 mm2/s] in NAION group and the differences were statistically significant (t=6.83, 7.10;P<0.05). The value of FA and Length in acute period, progressive period and chronic period of the NAION group decreased differently compared to the NCs group. At the same time, the value of MD value and λ┴in the three periods of the NAION group increased compared to the NCs groupand the differences were statistically significant (P<0.05). The value of FA between the acute period, the progressive period, and the chronic period of NAION group were statistically signficant (F=10.88, P<0.05). However, no significant differences were found in the values of MD, λ┴and Length of the NAION group (F=0.23, 0.64, 0.33, 1.38;P=0.79, 0.54, 0.72, 0.27). Conclusion The parameters of DTI can be used to monitor the damage of optic nerve and development in NAION.

Objective:To investigate the effects of Connexin-43 (Cx43) on osteoblasts proliferation and osteogenic differentiation and its regulatory mechanism.Methods:Osteoblasts were isolated and cultured in vitro. The osteogenic activity of osteoblasts was detected by alizarin red staining and alkaline phosphatase (ALP) staining after dexamethasone treatment. The expression of Cx43, Runt-related transcription factor 2 (Runx2), ALP, collagen I type (COL-I) and proliferation-related proteins PCNA and CDK4 in osteoblasts were detected by Western-blot. The expressions of osteoblast proteins were detected by immunofluorescence staining. The proliferation of osteoblasts was detected by CCK8 assay. The lentivirus-mediated Cx43 gene overexpression plasmid (Lv-Cx43) was constructed and transfected into osteoblasts. The osteogenic activity and proliferation ability of osteoblasts were further detected by the above methods. Cx43 in osteoblasts was overexpressed by pretreating PD98059. The osteogenic activity and proliferation of Cx43 in overexpressed osteoblasts was detected by CCK8 and alizarin red staining.Results:The isolated osteoblasts have osteogenic differentiation ability. Compared with the control group, 1×10 -6 mol/L dexamethasone treatment could reduce the formation of calcium nodules in osteoblasts. With the increase of dexamethasone treatment duration, the protein expression of Cx43, Runx2, ALP and COL-I in osteoblasts decreased gradually, while the expression of PCNA, CDK4 and p-ERK1/2 decreased. The OD values of normal osteoblasts at 0, 1, 2, 3 and 4 d were 0.316±0.043, 0.891±0.623, 1.683±0.154, 2.315±0.721 and 2.891±0.323, respectively. However, The OD values of osteoblasts treated with dexamethasone were 0.376±0.021, 0.657±0.121, 1.124±0.285, 1.521±0.272, 1.987±0.584, respectively. OD values of dexamethasone treated osteoblasts were lower than those of normal group at 2, 3 and 4 days ( P<0.05). The relative expression levels of Cx43 mRNA in control group, Lv-NC group and Lv-Cx43 group were 0.541±0.086, 0.598±0.018 and 1.000±0.082, respectively. The mRNA expression level of Cx43 in Lv-Cx43 group was higher than that in control group and Lv-NC group ( P<0.05). The ratio of Cx43 protein band to the gray value of GAPDH band in control group, Lv-NC group and Lv-Cx43 group were 0.816±0.737, 0.738±0.643 and 1.145±1.101, respectively. The expression level of Lv-Cx43 was higher than that in control group and Lv-NC group ( P<0.05). The expressions of Runx2, ALP, COL-I mRNA and related marker proteins in Lv-Cx43 group were higher than those in control group and Lv-NC group ( P<0.05). The number of calcium nodules in the Lv-Cx43 group was significantly higher than that in the control group and Lv-NC group. The OD value of osteoblasts and the number of calcium nodules in Lv-Cx43+PD98059 group were significantly lower than those in Lv-Cx43 group ( P<0.05). Conclusion:The proliferation and differentiation ability of osteoblasts is significantly decreased after the treatment of dexamethasone with decreased expression of Cx43. Overexpression of Cx43 can promote the proliferation and osteogenic differentiation of osteoblasts, which may be regulated through the ERK1/2 pathway.

Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.