ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

Objective:Exploring the clinical application effect of a series of digital designed guide plates in the repair of mandibular defects with free fibular muscle flap. Methods:A total of 32 patients who underwent fibular muscle flap repair of mandibular defects in the Head and Neck Tumor Surgery Department of Xi'an Jiaotong University Stomatological Hospital were selected as the research subjects. They were divided into a guide plate assisted group（16 cases） and a conventional surgery group（16 cases） according to the different surgical methods. The guide plate assisted group completed the surgery with the assistance of a digital design series of guide plates, while the conventional surgery group served as the control. Record the preparation and shaping time of two groups of fibular myocutaneous flaps, evaluate the surgical effect at least 6 months after surgery, and conduct a patient satisfaction survey. Use SPSS 16.0 software package to statistically process the data. Results:The preparation and shaping time of the fibular muscle flap in the guide plate assisted group were significantly shorter than those in the conventional surgery group（P<0.05）. The excellent and good rate（87.5%） of the guide plate assisted group in evaluating the surgical effect was significantly higher than that of the conventional surgery group（75.0%）（P<0.05）. The satisfaction scores of patients in the guide plate assisted group for facial shape and bite function recovery were significantly higher than those in the conventional surgery group（P<0.05）, while there was no significant statistical difference in the satisfaction scores of pronunciation function recovery between the two groups（P>0.05）. Conclusion:The design of digital guide plates can improve the accuracy of repairing mandibular defects with fibular flaps, shorten the preparation and shaping time of fibular flaps, restore good facial appearance and bite relationship of patients, and improve satisfaction. It is worth promoting and applying in clinical practice, but the design accuracy still needs to be continuously improved.
Humans ; Myocutaneous Flap ; Mandible/surgery* ; Fibula/transplantation* ; Plastic Surgery Procedures/methods* ; Male ; Free Tissue Flaps ; Female ; Middle Aged ; Mandibular Reconstruction/methods* ; Adult ; Patient Satisfaction

Objective:To compare the protective effects of cerebral blood flow during simulated push pull maneuver (PPM) between lower body negative pressure (LBNP) strategy and thigh cuff (TC) strategy.Methods:It was a repeated cross-over design study. Fifteen healthy young male subjects were recruited. All subjects underwent the control bout (simulated PPM without any intervention), PPM with LBNP bout, and PPM with TC bout. Such position changes as "upright to head down tilt to upright" were performed by tilting table to simulate PPM. The control bout underwent normal PPM. LBNP of -40 mmHg (1 mmHg=0.133 kP) was applied prior to and during -G z stress and released at the subsequent transition to +G z stress in LBNP bout. TC of +200 mmHg was applied at bilateral upper thighs prior to and during simulated PPM. Beat-to-beat cerebral and systemic hemodynamics of the subjects were continuously recorded. Results:During the rapid -G z to +G z transition, the mean cerebral blood flow velocity (CBFVm) was decreased by 0.7-17.3 cm/s [ΔCBFVm=(-7.5±4.5) cm/s], and the mean arterial pressure at the level of middle cerebral artery(MAP MCA) was decreased by 42-76 mmHg [ΔMAP MCA=(-61.0±10.0) mmHg] in control bout. However, the change of CBFVm was -2.4-10.2 cm/s in LBNP bout, whose average value was increased (3.3±4.1) cm/s rather than decreased. The drop of MAP MCA was 23-50 mmHg [ΔMAP MCA=(-41.0±11.0) mmHg], which was significantly reduced than that in control bout ( P<0.05). The change of CBFVm in TC bout was -7.9-1.4 cm/s [ΔCBFVm=(-3.0±4.2) cm/s], and the decrease of ΔMAP MCA was 37-59 mmHg [ΔMAP MCA=(-47.0±13.0) mmHg], both of which were significantly smaller than that in control bout ( P<0.05). There was significant difference in ΔCBFVm between LBNP and TC bouts ( P<0.05), while no significant difference was found in ΔMAP MCA. Conclusions:Both the LBNP and TC strategies can protect the cerebral blood flow during simulated PPM. LBNP strategy showed better improvement of CBFVm than TC. Both strategies demonstrated protective effect by increasing diastolic cerebral blood flow.

Objective:To compare the protective effects of cerebral blood flow during simulated push pull maneuver (PPM) between lower body negative pressure (LBNP) strategy and thigh cuff (TC) strategy.Methods:It was a repeated cross-over design study. Fifteen healthy young male subjects were recruited. All subjects underwent the control bout (simulated PPM without any intervention), PPM with LBNP bout, and PPM with TC bout. Such position changes as "upright to head down tilt to upright" were performed by tilting table to simulate PPM. The control bout underwent normal PPM. LBNP of -40 mmHg (1 mmHg=0.133 kP) was applied prior to and during -G z stress and released at the subsequent transition to +G z stress in LBNP bout. TC of +200 mmHg was applied at bilateral upper thighs prior to and during simulated PPM. Beat-to-beat cerebral and systemic hemodynamics of the subjects were continuously recorded. Results:During the rapid -G z to +G z transition, the mean cerebral blood flow velocity (CBFVm) was decreased by 0.7-17.3 cm/s [ΔCBFVm=(-7.5±4.5) cm/s], and the mean arterial pressure at the level of middle cerebral artery(MAP MCA) was decreased by 42-76 mmHg [ΔMAP MCA=(-61.0±10.0) mmHg] in control bout. However, the change of CBFVm was -2.4-10.2 cm/s in LBNP bout, whose average value was increased (3.3±4.1) cm/s rather than decreased. The drop of MAP MCA was 23-50 mmHg [ΔMAP MCA=(-41.0±11.0) mmHg], which was significantly reduced than that in control bout ( P<0.05). The change of CBFVm in TC bout was -7.9-1.4 cm/s [ΔCBFVm=(-3.0±4.2) cm/s], and the decrease of ΔMAP MCA was 37-59 mmHg [ΔMAP MCA=(-47.0±13.0) mmHg], both of which were significantly smaller than that in control bout ( P<0.05). There was significant difference in ΔCBFVm between LBNP and TC bouts ( P<0.05), while no significant difference was found in ΔMAP MCA. Conclusions:Both the LBNP and TC strategies can protect the cerebral blood flow during simulated PPM. LBNP strategy showed better improvement of CBFVm than TC. Both strategies demonstrated protective effect by increasing diastolic cerebral blood flow.

Objective:To study the prognostic value of left atrial strain in diastolic function response by treadmill exercise stress echocardiography.Methods:During May 2018 to February 2019, 64 patients underwent treadmill exercise stress echocardiography for diastolic function evaluation in Tangdu Hospital, Air Force Medical University, were recruited.Patients were categorized into diastolic stress test negative group (pre-stress E/e′ <14 & post-stress E/e′<14) (DST- group), and diastolic stress test positive group (pre-stress E/e′ <14 & post-stress E/e′>14) (DST+ group). Patients′ characteristics of the stress test, left ventricular diameter, left atrial volume index, systolic and diastolic function, and left atrial strain parameters were compared between these two groups. ROC analyses were performed based on the echocardiographic parameters with significant group differences ( P<0.01) to determine the predictive values for diastolic stress test response. Results:The pre-stress E/e′ and left atrial strain parameters were significantly differently between DST- and DST+ group. The DST- showed significantly lower E/e′ (8.20±1.27 vs 10.32±1.33, P<0.01), but higher left atrial strains than DST+ group[reservoir function(33.7±5.7)% vs (26.5±5.5)%, P<0.01; conduit function(16.8±4.0)% vs (11.8±3.4)%, P<0.01; pump function(16.9±5.7)% vs (14.7±5.5)%, P<0.05]. The left atrial reservoir function, conduit function and pre-stress E/e′ could predict the diastolic stress test response, the areas under ROC curve were 0.81 ( P<0.01), 0.62 ( P=0.04) and 0.71 ( P<0.01). Conclusions:The left atrial strain parameters under resting condition could predict the diastolic stress test response. It may serve as an alternative method of exercise stress echocardiography for diastolic function evaluation.

Objective To observe the clinical effect of platelet-rich fibrin (PRF) on prevention of postoperative hemorrhage and facial traumatic swelling in patients with mandibular angle osteotomy.Methods Twenty-five patients with mandibular angle hypertrophy were included in this study from January 2014 to November 2015.Split face comparative study was carried out to use the left and right sides as the experimental side and the control side,respectively.The PRF in the experimental side was placed in the mandibular osteotomy,while the control side was placed in platelet-poor plasma (PPP).After operation,the drainage volume and facial swelling degree were measured.Results The drainage volume of the experimental group (PRF group) was (20.35 ±7.40) ml,the control group (PPP group) was (43.23±11.96) ml,and the difference was statistically significant (P＜0.05).There was no such case without swelling in postoperative third day.The facial swelling score on the experimental side was (1.19±0.40),the control side was (2.62±0.64),and two groups of postoperative facial swelling scores were significantly different (P＜0.05).Conclusions The PRF can reduce postoperative bleeding and facial swelling after mandibular angle osteotomy.