Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.

BACKGROUND: Stent failure is more likely in the lipid rich and thrombus laden culprit lesions underlying ST-segment elevation myocardial infarction (STEMI). This study assessed the effectiveness of post-dilatation in primary percutaneous coronary intervention (pPCI) for acute STEMI. METHODS: The multi-center POST-STEMI trial enrolled 41 consecutive STEMI patients with symptom onset <12 hours undergoing manual thrombus aspiration and Promus Element stent implantation. Patients were randomly assigned to control group (n=20) or post-dilatation group (n=21) in which a non-compliant balloon was inflated to >16 atm pressure. Strut apposition and coverage were evaluated by optical coherence tomography (OCT) after intracoronary verapamil administration via thrombus aspiration catheter, post pPCI and at 7-month follow-up. The primary endpoint was rate of incomplete strut apposition (ISA) at 7 months after pPCI. RESULTS: There were similar baseline characteristics except for stent length (21.9 [SD 6.5] mm vs. 26.0 [SD 5.8] mm, respectively, P=0.03). In post-dilatation vs. control group, ISA rate was lower (2.5% vs. 4.5%, P=0.04) immediately after pPCI without affecting final TIMI flow 3 rate (95.2% vs. 95.0%, P>0.05) or corrected TIMI frame counts (22.6±9.4 vs. 22.0±9.7, P>0.05); and at 7-month follow-up (0.7% vs. 1.8%, P<0.0001), the primary study endpoint, with similar strut coverage (98.5% vs. 98.4%, P=0.63) and 1-year rate of major adverse cardiovascular events (MACE). CONCLUSION In STEMI patients, post-dilatation after stent implantation and thrombus aspiration improved strut apposition up to 7 months without affecting coronary blood flow or 1-year MACE rate. Larger and longer term studies are warranted to further assess safety (ClinicalTrials.gov identifi er: NCT02121223).

This study analysed the changes of the soil micro-ecology in the process of soil sterilization, green manure returning farmlands and fertilization. The methods of soil improvement was initially built which ensured the successful proceed of ginseng cultivation in farmlands. The soil chemical properties were analysed, the diversity and composition of bacterial community after soil sterilization, sterilization+green manure returning farmlands and sterilization+green manure returning farmlands+fertilization. The results exhibited that measures of soil improvement decreased the pH, increased soil fertility, declined the diversity of bacterial community and changed the composition of soil bacterial community. The comprehensive measures of sterilization+green manure returning farmlands+fertilization decreased the ginseng death rate compared to the control. Our data indicated that soil micro-ecological environment was changed by the treatments of soil sterilization, sterilization+green manure returning farmlands and sterilization+green manure returning farmlands+fertilization, and comprehensive measures improved the survival rate and guaranteed the development of ginseng cultivation in farmlands.

Acute Disease ; Adult ; Fatal Outcome ; Humans ; Male ; Neoplasm Recurrence, Local ; diagnosis ; drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy

OBJECTIVETo explore the mechanism of acupotomy lysis in treatment of the third lumbar vertebrae transverse process syndrome.

METHODSOne hundred and eighty patients were randomly assigned into an acupotomy group and an electroacupuncture (EA) group, 90 cases in each group. The acupotomy group was treated with acupotomy on the tip of the 3rd lumbar vertebrae transverse process (tender point) combination with massage manipulation of hyperflexion and hyperextension on the waist, once a week for 3 weeks. The EA group was treated with EA at bilateral Shenshu (BL 23), Yaoyangguan (GV 3), Ashi point (local tender point) and ipsilateral Weizhong (BL 40), 3 times a week for 3 weeks. The 500 g pressure displacement and the energy absorption ratio were measured by JZL-II soft tissue tension meter and the clinical effect was evaluated by JOA low back pain scale before treatment, after treatment and 6 months after treatment.

RESULTSAfter treatment and at follow-up visit, the 500 g pressure displacement in the acupotomy group increased significantly (both P < 0.01), but it was decreased significantly in the EA group (P < 0.05, P < 0.01). The energy absorption ratio in the acupotomy group after treatment and at follow-up visit increased significantly (both P < 0.01), and in the EA group, there was no significant difference after treatment as compared with that before treatment (P > 0.05), but it was increased significantly at follow-up visit (P < 0.01). The total therapeutic level distribution in the acupotomy group was better than that in the EA group after treatment and 6 months after treatment (P < 0.05, P < 0.01).

CONCLUSIONAcupotomy therapy can significantly increase the 500 g pressure displacement and the energy absorption ratio of the local soft tissue around the third lumbar vertebrae transverse process, decrease the local soft tissue tension so as to alleviate pain. The clinical effect of the acupotomy is superior to that of electroacupuncture.

Acupuncture Points ; Acupuncture Therapy ; methods ; Adult ; Aged ; Electroacupuncture ; Humans ; Lumbar Vertebrae ; Middle Aged ; Spinal Diseases ; physiopathology ; therapy ; Syndrome

Animals ; Flunarizine ; pharmacology ; Hippocampus ; drug effects ; physiopathology ; Male ; Neurons ; drug effects ; physiology ; Penicillins ; adverse effects ; Rats ; Rats, Wistar ; Seizures ; chemically induced ; physiopathology

Objective To investigate the effect of transplantation of human umbilical cord blood mesenchymal stem cells (CB-MSCs) on the levels of NGF and BDNF in rats with traumatic brain injury (TBI) and explore its possible mechanism of cerebral protection. Methods Ninety healthy male SD rats were equally randomized into sham-operated group, injury control group and treatment group.TBI models in the injury control group and treatment group were induced by the improved device of Feeney weight-dropping; the rats in the treatment group were injected Brdu-labeled 3×106 CB-MSCs solved in 1ml PBS by rat-tail vein, while the rats in the sham-operated group and the injury control group were injected the equal volume of PBS solution. No immunosuppressive agents were used in all the rats.HE staining, immunohistochemistry, in-situ hybridization were employed, respectively, to detect the morphological changes, Brdu positive cells, expressions of BDNF and NGF on the 3rd, 7th, 14th, 21st and 28th d of injection. Results Only a very small number of nerve cells were BDNF and/or NGF positive in the sham-operated group. Substantial BDNF and/or NGF positive cells in the injury control group were noted in the surrounding brain damaged area following traumatic brain injury, which peaked at their levels on about 14 d of injection (the A value of NGF=8.35±1.07, that of BDNF=9.01±1.74), following by a gradual decline; however, significant difference was still noted as compared with that in the sham-operated group (P＜0.05). BDNF and/or NGF-positive cells significantly increased in the treatment group, especially in the surrounding brain injured areas; their levels peaked on the 14th d of injection,following by a gradual decline on the 21st and 28th d, but they were still higher than those in the injury control group and sham-operated group at each time points (P＜0.05). Conclusion Transplantation of CB-MSCs can increase the secretion of BDNF and NGF in rats with TBI, improve the local micro-damage environment and promote the repair of neurons.

This study was aimed to detect the telomere length and the telomerase expression activity in patients with chronic lymphocytic leukemia (CLL), and investigate their relation to prognosis of CLL. The telomere length and the telomerase expression activity of peripheral blood and / or bone marrow mononuclear cells were examined by Tel-FISH, a semi-quantitative method and by TRAP-ELISA respectively; the expressions of ZAP70 and CD38 were detected by flow cytometry. The results showed that comparing the telomere length in different stages, there was a tendency that the telomere became prolonged when the stage raised up. There was statistical significant difference between Rai stages III-IV and stage 0, Rai stages III-IV and stages I-II, Binet stage C and stage A, Binet stage C and stage B; while no statistical significant difference existed between Rai stage 0 and stages I-II, Binet stage A and stage B. The telomere length in ZAP70 negative group was found similar as in ZAP70 positive group. The telomere length in CD38 positive group was shorter than that in CD38 negative group, but there was no statistical difference between them. Comparing the telomerase expression activity between different stages, there was a tendency that it increased when the stages went up; comparing the telomerase expression activity at different Rai stages, it increased at the higher stages. One case of CLL demonstrated that telomerase expression did not show at remission stage, but was found at relapse stage, which suggested that telomerase expression may relate to prognosis of disease. It is concluded that the telomerase length is in relation to Rai and Binet stage, which was shorter at higher stage than that at lower stage and intermediate stage. It seemed that the telomerase expression activity increased at higher stages. The expression of telomerase in mononuclear cells is stable and not influenced by treatment.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Male ; Middle Aged ; Telomerase ; metabolism ; Telomere ; genetics

OBJECTIVETo observe the effects of auricular acupuncture on the learning and memory abilities of model rats with Alzheimer's disease (AD), and investigate its mechanism.

METHODSThirty SD rats were randomly divided into a control group, a model group and an auricular acupuncture group, 10 rats in each group. The model rats with AD were established by multiple injections with Okadaic Acid into the CA1 region of hippocampus. In the control group, the same quantity injection with Dimethyl Sulfoxide (DMSO) was applied on experimental rats. The auricular acupoints of "Nao" (brain) and "Shen" (kidney) were used for treating in the auricular acupuncture group, in contrast, the auricular region were not treated in the model and the control groups. The learning and memory capabilities of the rats were assessed with Morris Water Maze behavioral test, and the expressions of choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry.

RESULTSComparing with the model group, the treated AD rats with auricular acupuncture was showed that the average escape latency was obviously shortened in the place navigation test (P<0.01), the movement time in plateform quadrant was obviously prolonged in the spatial probe test (P<0.05), and the number of traversing platform obviously increased (P<0.01) after the platform was taken away. The expression of ChAT increased in the hippocampus and cortex (P<0.01, P<0.05), but the expression of GFAP obviously decreased in the CA1 region of hippocampus (P<0.01).

CONCLUSIONAuricular acupuncture can improve the learning and memory capability of the model rats with AD. Its mechanism might be related with decreasing cholinergic neuron damage and reducing the abnormal activation and hyperplasia of astrocyte.

Acupuncture, Ear ; Alzheimer Disease ; genetics ; metabolism ; psychology ; therapy ; Animals ; Choline O-Acetyltransferase ; genetics ; metabolism ; Disease Models, Animal ; Gene Expression ; Glial Fibrillary Acidic Protein ; genetics ; metabolism ; Humans ; Male ; Memory ; Random Allocation ; Rats ; Rats, Sprague-Dawley