BACKGROUND:Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems.Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway,but are limited to their easy agglomeration and colloidal morphology,which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE:To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS:The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold.The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized.The microstructure,porosity,permeability,rheology,in vitro hemostasis,and antibacterial properties of the composite hydrogel were characterized.The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining,and the optimization effects of low-intensity pulsed ultrasound on the permeability,porosity,and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION:(1)Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers.The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability.(2)Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility.(3)Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure,and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation.The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials.The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold.Under the irradiation of low-intensity pulsed ultrasound,the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties.(4)Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles,and more uniform dispersion could be obtained under ultrasonic excitation.(5)The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets,which showed stronger mechanical properties.The elongation at break was 122%,and the ductility was better than that without gold nanoparticles-nanodroplets(P<0.05).(6)These findings indicate that the composite hydrogel scaffold has good biocompatibility,antibacterial property,oxidation resistance,and hemostatic effect.

Objective:To compare 3D-printing-assisted surgery and conventional surgery in the treatment of Schazker type Ⅵ tibial plateau fractures.Methods:A retrospective study was conducted to analyze the clinical data of 50 patients with type Ⅵ tibial plateau fracture who had been treated from January 2019 to December 2021 at the 5 Departments of Orthopedics in The First Affiliated Hospital of Nanchang University, The First People's Hospital of Jiujiang, Pingkuang General Hospital, Ganzhou People's Hospital, and Nanchang Hongdu Hospital of Traditional Chinese Medicine. The patients were divided into 2 groups according to their different treatment methods. In the 3D printing group of 25 cases treated by 3D-printing-assisted surgery, there were 14 males and 11 females, with an age of (42.5±9.1) years; in the conventional group of 25 cases treated by conventional surgery, there were 13 males and 12 females with an age of (42.2±9.3) years. The 2 groups were compared in terms of operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, fracture healing time, postoperative complications, the Rasmussen radiological scores and the American Hospital for Special Surgery (HSS) knee function scores at 6 and 12 months after operation.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The operation time [(125.4±10.6) min], intraoperative blood loss [(206.2±16.3) mL], intraoperative fluoroscopy frequency [(9.2±2.7) times] and fracture healing time [(3.0±0.7) months] in the 3D printing group were all significantly less than those in the conventional group [(168.2±14.1) min, (303.2±20.4) mL, (15.5±3.5) times and (4.1±0.8) months] while the Rasmussen radiological scores (17.6±1.2 and 17.9±0.6) and HSS knee scores (90.8±6.4 and 91.5±5.6) at 6 and 12 months after operation in the 3D printing group were all significantly higher than those in the conventional group (16.2±2.6 and 16.7±2.2; 84.5±9.2 and 87.6±8.0) (all P<0.05). In the 3D printing group, there were 1 case of wound infection and 1 case of wound dehiscence after operation. In the conventional group, there were 2 cases of wound skin necrosis, 3 cases of wound dehiscence, 1 case of traumatic arthritis, 2 cases of wound infection, and 1 case of screw loosening. The incidence of complications in the 3D printing group (8.0%, 2/28) was significantly lower than that in the conventional group (36.0%, 9/25) ( P<0.05). Conclusion:In the treatment of Schatzker type VI tibial plateau fractures, compared with conventional surgery, 3D-printing-assisted surgery can lead to better curative outcomes, because it is conducive to lowering surgical difficulty, reducing postoperative complications, and promoting fracture union and functional recovery of the knee.

Objective:To construct a biospecimen bank of patient derived organoids (PDOs) from pancreatic cancer tissues and to explore the feasibility of PDOs drug sensitivity assay technology to guide chemotherapy drug selection for pancreatic cancer.Methods:Pancreatic cancer tissue specimens obtained after surgical resection and puncture biopsy from Mar 2020 to Dec 2022 at Drum Tower Hospital, Nanjing University School of Medicine were collected. Pancreatic cancer PDOs were cultured in vitro and histologically identified; PDOs were treated with gemcitabine, Nab-paclitaxel, fluorouracil, Oxaliplatin, and Irinotecan and cell viability was measured to analyze the correlation between PDOs drug sensitivity and the actual clinical treatment response.Results:The PDOs can reproduce the pathological features of corresponding tumor tissues; the sensitivity of different PDOs to the same chemotherapeutic drug is significantly different; The sensitivity of PDOs was highly consistent with the actual treatment effect of the corresponding patients 75.76% (25/33); organoid organ-based susceptibility testing had predictive value for the treatment response of patients (AUC=0.733, 95% CI: 0.546-0.919, P<0.05). Conclusion:A biobank of pancreatic cancer PDOs was successfully constructed, and the drug susceptibility test results were significantly correlated with the actual medication response of patients, suggesting that the drug susceptibility test technology based on PDOs has the potential to guide individualized chemotherapy for pancreatic cancer.

Objective To establish Cdh5-Cre ERT /Acta2-tdTomato-STOP floxed -eGFP knockin genetic tracing mice, and to investigate its application in studies on vascular endothelial cell transition in liver fibrosis. Methods Cdh5-Cre ERT mice were mated with Acta2-KI mice, and the Cdh5-Cre ERT /Acta2-KI genetic tracing mice were obtained and identified by PCR genotyping. Primary liver sinusoid endothelial cells (LSECs) were isolated and cultured, and a model of CCl 4 -induced liver fibrosis was established. LSECs and liver tissue were collected for immunofluorescent staining to observe the expression of the fluorescent proteins tdTomato and eGFP. Results After being induced by tamoxifen, LSECs and liver tissue of Cdh5-Cre ERT /Acta2-KI genetic tracing mice expressed eGFP under the conditions for epithelial-mesenchymal transdifferentiation established in vivo and in vitro, while the control group without induction expressed tdTomato alone. Conclusion The successfully established Cdh5-Cre ERT /Acta2-KI genetic tracing mice can realize the effective labeling of epithelial-mesenchymal transdifferentiation, which provides a genetic tracing basis for the diverse sources of mesenchymal myofibroblasts in liver fibrosis.

Objective: To study the expression and distribution of filaggrin (FLG) in oral submucous fibrosis (OSF) and to explore the significance of FLG in the occurrence and development of OSF. Methods : Ten cases with a normal oral mucosa (normal buccal mucosa group) and 30 cases of tissues with OSF lesions, including 10 cases each in the early (early OSF group), moderate (middle OSF group) and advanced stages (late OSF group), were selected. FLG was analyzed by immunohistochemistry. The FLG-positive cells were counted to calculate the percentages of cells with FLG-positive expression in each group. Results: FLG expression was negative in most of the normal buccal mucosa group specimens and was positive in the OSF buccal mucosal epithelial specimens. With aggravation of the OSF lesion, the number of FLG-positive cells increased. In the early OSF group, FLG-positive expression was mainly concentrated in the granular and keratinized epithelial layers. In the middle OSF group, the number of FLG-positive epithelial cells increased gradually. In the late OSF group, almost all epithelial cells were FLG-positive in the cytoplasmic nucleus. The percentages of FLG-positive cells in the early, middle and late OSF groups were (24.63 ± 9.06)%, (54.23 ± 10.63)% and (83.97 ± 8.72)%, respectively. The percentage of FLG-positive cells was significantly higher in the OSF group than in the normal mucosa group (P < 0.05). Conclusion FLG was expressed at a higher level in the OSF epithelium than in the normal oral mucosal epithelium and was upregulated in the OSF epithelium with aggravation of the OSF lesions. Abnormal FLG expression may be related to the terminal differentiation disorder of OSF epithelial keratinocytes.

Objective To investigate the status and influencing factors of pleasant events among community-dwelling dementia patients. Methods Totally 266 community-dwelling dementia patients were recruited from Bei-jing,Guangzhou and Tianjin,and were investigated with the Chinese-version Pleasant Events Schedule-AD(PES-AD). Results The overall score of PES-AD was (14.0±6.7). The factor scores from high to low were sensory stimulation activities(0.9±0.5),family activities(0.8±0.5),emotional stimulation activities(0.8±0.4) and autonomy activities(0.6± 0.5). Multiple linear regression showed that the severity of disease,without chronic disease,educational level of de-mentia patients and their caregivers were significant influencing factors of pleasant events,which explained 41.1% of the total variance. Conclusion Sensory stimulation activities of community-dwelling dementia patients were relatively satisfactory,followed by family activities and emotional stimulation activities,but autonomy activities were relatively unsatisfactory. It is suggested to choose appropriate pleasant activities according to the severity of disease for de-mentia patients to improve their quality of life.

Objective To review psychopathic individuals' moral judgments and the underlying neural mechanisms in order to provide cognitive basis and the corresponding intervention for their socially deviant behavior.Methods Literatures were searched in Academic Search Premier,Science Direct,Highwire,PubMed and Wanfang database by July 2015.Index strategy:AB [psychopathy OR psychopathic] AND AB [moral judgments OR moral reasoning].Forty-seven articles including six in Chinese were chosen based on their abstracts and key words.Results 33 papers were adopted finally including 2 in Chinese.Most of the papers involved representative empirical studies within five years.Conclusion Compared with non-psychopathic individuals,psychopathic individuals are inclined to consider moral transgressions as more acceptable and are more inclined to make utilitarian moral judgments.Their impairment in moral judgments is associated with dysfunction in specific brain regions such as amygdale,dorsolateral prefrontal cortex,and ventromedial prefrontal cortex,and dysfunction in the basic brain system.Psychopathic individuals' moral judgment impairment needs to be examined within the frame of affect and their moral reasoning processes should be investigated in the future.

Aims To synthesize acetylated low molecu-lar weight heparin( ALMWH) and to detect its physico-chemical properties and antineoplastic activity. Meth-ods LMWH was prepared by degradation of UFH with sodium periodate oxidation and sodium borohydride re-duction, then the LMWH was acetylated by acetic an-hydride where N, N′, -dicyclohexylcarbodiimide ( DCC ) and 4-dimethylaminopyridine ( DMAP ) were used as catalysts. X-ray diffraction(XRD)and Differ-ential Scanning Calorimetry ( DSC ) of ALMWH were obtained. The antiproliferative activity and anti-inva-sive activity were determined on MDA-MB-231 and MCE-7 human breast cancer cells. Results XRD a-nalysis showed that the LMWH degraded from UFH and ALMWH synthesized by acetylation of LMWH be-longed to amorphous structure, however, their DSC curves were significantly different. Compared with LM-WH, ALMWH had more powerful capacity for binding water and lowering anticoagulant activity, more signifi-cantly ALMWH exhibited stranger anti-proliferative and anti-invasive activity than LMWH, especially when it was used in low concentrations. Conclusion The syn-thesized ALMWH possesses a low anticoagulant activi-ty, certain anti-proliferative, anti-invasive and anti-metastatic activity. This study provides a basic method for screening of antineoplastic drug with low toxicity.

Objective To examine the effect of risperidone on the mental symptoms after frontotemporal brain contu?sion. Methods Sixty cases with mental symptoms after frontotemporal brain contusion were recruited from Jan 2009 to Dec 2011 and were randomly divided into control group and treatment group. The patients in the control group were giv?en vitamin B1 60mg/d, while the patients in the treatment group were given risperidone 1mg/d. Both groups were treated for 1 month. Positive and negative symptom scale (PANSS) and symptom scale (TESS) were used to evaluate the efficacy and adverse reactions of treatment. Results The PANSS score was significantly lower in the treatment group than in con?trol group at 1, 2, 3 and 4 weeks following treatment(difference between groups:F=48.12 ,P<0.0001;Time difference:F=290.99 ,P<0.0001; Interaction between group and time: F=11.91,P<0.0001 ). After time-adjustment, the PANSS score was significantly lower in the treatment group than in control group at 2, 3 and 4 weeks following treatment. In the course of treatment, the patients in both groups had varying degrees of headache, nausea, weight gain and Beckoning. These side effects were alleviated through symptomatic treatment. Conclusion Risperidone can significantly improve psy?chiatric symptoms in patients with frontotemporal brain contusion with satisfactory safety.

Objective To evaluate the anticoagulant and antineoplastic activities of chemically modified low-molecular-weight heparin (LMWH). Methods LMWH obtained by splitting unfractionated heparin (UFH) with sodium periodate oxidation and sodium borohydride reduction was subjected to acetylation catalyzed by DCC and DMAP to produce acetylated LMWH (ALMWH). The anticoagulant activity of ALMWH was determined in mice, and its antiproliferative and anti-invasion activities was assessed in human breast cancer cells MDA-MB-231 and MFC-7. Results The anticoagulant activity of LMWH was decreased significantly after acetylation. The concentrations of commercial LMWH* and ALMWH for doubling the coagulation time (CT) were 33.04 μmol/L and 223.56 μmol/L, respectively, and the IC50 of ALMWH for doubling CT was 6 times of that of LMWH*. ALMWH and LMWH at 0.1, 0.3, 0.9, 2.7 and 8.1 mmol/L both significantly inhibited the proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner, but ALMWH produced stronger inhibitory effects. The IC50 of LMWH and ALMWH for inhibiting cell proliferation was 3168.4 μmol/L and 152.6 μmol/L in MCF-7 cells, and 12299.6 μmol/L and 22.2 μmol/L in MDA-MB-231 cells, respectively. ALMWH and LMWH all markedly suppressed the invasion of MDA-MB-231 cells with comparable effects. Conclusion Chemical modification of structure can endow LMWH with a low anticoagulant and high antiproliferative activities.