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: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 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.

Objective Aged facial contour presents changing facial skeleton and sagging soft tissue.We performed reshaping the facial skeleton simultaneouly during the rhytidectomy to achieve a youthful facial contour.Methods It was a retrospective observational study based on 26 elderly women (42-60 years) that complained of aged face and boosing of the orbital rim,prominent zygoma and mandibular angle.All of them had undergone reduction boosing,malar and mandible combined with rhytidectomy from January 2010 to December 2015.Results The facial skeleton was reshaped with face-lift successfully.No fatal bleeding,respiratory obstruction,cardiovascular accident,severe facial edema,permanent facial nerve injury and other major complications occurred.All of the patients recovered safely.Follow-up for 3-24 months showed that the facial contour and aging were improved,and the youthful face form was preserved.Conclusions The face contour correction combined with face-lift is an effective technique to restore the youthful for elderly patients.

Objective To summarize the experience of clinical application of combining double suture fixation and resection of partial fat retro-orbicularis oculus in some specially difficult blepharoplasty.Methods During upper blepharoplasty,patients with heaviness and bulkiness in the both upper eyelid and lateral upper orbital region,we combined double suture fixation and resection partial fat retro-orbicularis oculus.First,partial pretarsal bulky fat was resected,and to form skin-orbicularisoculi composite below incision line.And then,some thickened fat retro-orbicularis oculus was resected,which was also named preseptal and retro-orbicularis oculus fat (ROOF).Double suture fixation techniques were applied to form dynamic and physiological double eyelid.Results 146 cases had satisfactory effectiveness,except for 2 cases with secondary operation because of some superficial double eyelid creases,and 1 case had hematoma,and 3 had transient numbness in the lateral supraorbital nerve region.They were satisfied with healthy eyelid skins,concealed incision and non-serious complications followed at 3-24 months postoperatively.Conclusions Combining double suture fixation and resection of partial fat retro-orbicularis oculus would appear to be a useful adjunct to standard blepharoplasty techniques in selected patients.

Objective To determine the central venous pressure (CVP) noninvasively based on hemodynamics principles using ultrasound location of the collapse point of the internal jugular vein.Methods Forty patients were enrolled in this study.The collapse point of the internal jugular vein was located and marked by a linear transducer,the body mark of right atrium was marked on the right lateral wall of the chest.The noninvasive CVP was calculated according to the vertical distance between those two points.The invasive CVP determination by central venous catheter was also carried out on all the patients.Correlation analysis was used to compare the invasive and noninvasive methods.With invasive determination of CVP as the gold standard,the ROC curve of the noninvasive ultrasound method was sketched to explore the optimal cut-off points.Results The correlation analysis reveal high positive correlation between CVPs determined by ultrasound imaging and central venous catheter (r =0.906,P ＜0.01).By the ROC curve test,fluid column height of 10.75 cm by ultrasound method was determined as the cut-off point,with the sensitivity and specificity of diagnosing elevation of CVP being 88.9％ and 93.5 ％ respectively.The corresponding area under the curve was 0.971.Conclusions Ultrasound imaging could be used to determine CVP noninvasively,which would be helpful in diagnosis of the circulating load of patients.

Objective To propose an accurate method of noninvasive determination of central venous pressure(CVP ) by locating the central point of right atrium (RA ) using echocardiography .Methods Through the 3D reconstruction ,the accurate positions of RA of 30 patients who had been examined by multislice 3‐dimensional computed tomography for chest imaging were recorded .Based on solid geometric principles ,the central point in RA was located by echocardiography and then compared with CT‐location point .The accuracy and feasibility were assessed by absolute distance (Da) ,vertical distance (Dv) and the whole time of location (T) between the two points .Results Mean Da ,Dv and T of the whole subjects were 07.6cm(95% CI:06.2to08.1cm),01.6cm(95% CI:-00.2to03.4cm),and438.0s(95% CI:400.1to 47 4.0 s) ,respectively .Conclusions The echocardiographic method on the basis of solid geometry proposed in this study could be used to locate the central point in RA accurately and simply .Thus it would be helpful to improve the accuracy of noninvasive determination of central venous pressure .