AIM:To establish an effective and rapid method to develop transplanted subcutaneous pancreatic carcinoma by inducing PANC-1 cells into nude mice, and then use this mouse model to evaluate the tumor-homing and gene-silencing effects of siRNA-loading nanoparticles in vivo.METHODS:Different numbers of PANC-1 cells in 100 μL or 300 μL PBS were inoculated subcutaneously into the right flank of BALB /c (nu/nu) mice.When the tumor volume reached 100 mm 3 , siRNACY 5.5 nanoparticles were injected through the mouse tail vein to perform in vivo imaging assay.Be-sides, the mice were randomly divided into 3 treatment groups treated with PBS, scrambled control RNA nanoparticles and siKras nanoparticles, respectively.The protein expression of Kras was detected by Western blotting and immunohistochemi-cal staining.RESULTS:After inoculated with 1 ×10 7 PANC-1 cells in 300 μL PBS, all mice developed tumors within 2 weeks.The in vivo results showed that siRNA-loading nanoparticles accumulated in the tumor tissues and exerted gene si-lencing effect.CONCLUSION:In the present study, an effective and rapid method was established for PANC-1 cells to induce transplanted subcutaneous pancreatic carcinoma in nude mice within 2 weeks, which is suitable for in vivo imaging and treatment evaluations as a reproducible and reliable way for the further experiments .

Background Endothelin-1 (ET-1) is an active regulator of intraocular pressure.The ET-1 level in aqueous humor is elevated in primary open-angle glaucoma,normal intraocular tension glaucoma and the animal model of glaucoma.There is now accumulating evidence for a role of ET-1 in the pathogenesis of glaucoma.However,the effect of ET-1 on the phagocytic function in trabecular meshwork cells (TMCs) is unclear.ObjectiveThis study is to observe the effect of ET-1 on the phagocytic function in cultured human TMCs.Methods Human trabecular meshwork tissue was obtained from healthy donator and cultured and subcultured in vitro by the explant culture method.The third passage of human TMCs were incubated with fluoresent red-labeled latex beads for 0,4,8,12,24,48 and 72 hours.The phagocytic kinetics of human TMCs were continuously evaluated by counting the number of latex beads in TMCs using a fluorescence microscope.Depending on the concentrations of ET-1 in culture medium,the TMCs were divided into control group (without ET-1),low-dose ET-1 (10~(-9)mol/L) treatment group,middle-dose ET-1 (10~(-8)mol/L) treatment group and high-dose ET-1 (10~(-7) mol/L) treatment group.In addition,based on the addition of endothelin receptor (ETAR) antagonist,the TMCs were divided into control group (without ETAR antagonist),ET-1 (10~(-8)mol/L) treatment group,ETAR antagonist (1×10~(-7)mol/L BQ123+10~(-8)mol/L ET-1) treatment group and ETBR antagonist(1×10~(-7) mol/L BQ788+10~(-8) mol/L ET-1)treatment group.TMCs of each group were incubated with latex beads,and the numbers of latex beads in TMCs were counted under a fluorescent microscope.Results Cultured HTM cells showed positive reactions for FN,LN,NSE and negative response for FⅧRag.The phagocytic kinetics test revealed that the latex beads were detected 4 hours after incubation.The density of latex beads was gradually increased with the delay of incubation duration and peaked at 24 hours.The number of the latex beads saturated after 48 hours of incubation.However,the number of latex beads in TMCs was significantly reduced after the addition of ET-1 in a dose-dependent manner (F=28.91,P＜0.05).The number of latex beads in the ET-1 group was less than that in the control group and the ETAR receptor antagonist group (q=13.7228,q=9.4312,P＜0.05).No significant difference was found in latex beads number between the ET-1 group and the ETBR antagonist group (q=1.1600,P＞0.05).Conclusion ET-1 inhibits the phagocytic function of human TMCs and ETAR plays a partial role in the phagocytic function of human TMCs.

In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 (cdk-5) inhibition in mice with Niemann-Pick disease type C (NPC) (npc(-/-)), recombinant adeno-associated virus (rAAV) carrying the small interfering RNA (siRNA) specific for cdk-5 gene was injected into 3-day-old npc(-/-) mice intracerebroventricularly. The rAAV-GFP-injected age-matched npc(-/-) mice and non-surgery age-matched npc(-/-) mice were employed as controls (n=6-10/group). From the 4th to 8th week after the treatment, mice were weighed, and evaluated for limb motor activity by using the coat hanger test once a week. Eight-week-old npc(-/-) mice were sacrificed by decapitation, and brains were quickly dissected and halved sagittally. Immunohistochemistry, Western blotting, and HE staining were used to evaluate the neuropathology in npc(-/-) mice. The results showed that rAAV-cdk-5-siRNA-GFP significantly reduced the number of axonal spheroids, delayed the death of Purkinje neurons, ameliorated motor defects in npc(-/-) mice, and significantly attenuated the hyperphosphorylation of tau proteins. These data suggested that inhibition of cdk-5 activity has neuroprotective effect on neurons in NPC mice.

Technologies for glycomics usually involve methods for separation and purification of poly-saccharides, and separation, structure resolution, quantification, property investigation and function comment of glycan chains. Because of the different biochemical properties of glycoproteins, proteogly-cans and glycolipids, the separation and purification of polysaccharides involve corresponding fractional precipitation, boric acid affinity, titanium dioxide, affinity chromatography, size exclusion method, and gel filtration chromatography column chromatography methods. The lectins, water affinity chromatogra-phy , solid phase extraction and other technologies could be applied to the oil enrichment of high pure and specific glycan chains. The structure of glycan chains can be analyzed using lectin microarray technolo-gy, mass spectrometry, and derivatization markers of glycan chains. lsotope labelling and metabolic labeling can be used to quantify glycan chains. The glycan biological function can be better understood using glycan chain structure analysis software and database of glycan chains by bioinformatics.

Objective To examine the influence of systemic rehabilitation exercise on social functioning in chronic schizophrenic patients.Methods 60 qualified cases selected from chronic psychiatric inpatient department were randomly divided into two groups according to admission number (AD).30 cases in treatment group accepted hospitalized systemic rehabilitation exercise and 30 controls accepted ordinary treatment for 6 months.Social functio-ning evaluated with SSPI and PSP.Results The total score of SSPI(t=1.322,P=0.256) and PSP(t=1.563,P=0.362) were not significantly higher(P>0.05),The total score of SSPI [(37.44 ±4.33)points,t=2.719,P=0.001]and PSP[(72.14 ±6.86)points,t=3.985,P=0.000]total score in the treatment group were significantly higher than that in the control group(P<0.01).It were significantly higher in the treatment group than before the intervention.The total score of SSPI (t=0.385,P=0.763)and PSP(t=0.682,P=0.827) total score were not significantly higher in the control group(P>0.05).Conclusion Systemic rehabilitation training does influence on social functioning in chronic schizophrenic patients.

Objective To analyze the relationship between soluble α-Klotho(SKL)levels and continuous glucose monitoring(CGMS)-derived measures of glycemic management in diabetic kidney disease(DKD)patients.Methods A total of 140 T2DM patients admitted to the Department of General Medicine Affiliated Hospital of Yan'an University from May 2020 to May 2022 were selected and divided into two groups according to the levels of UACR:T2DM group(UACR<30 mg/g,n=60),DKD group(UACR≥30 mg/g,n=80)and 45 healthy persons(NC group)who received physical examination in the hospital during the same period were the NC group.Results The SKL level of DKD group was lower than that of T2DM group and NC group(P<0.05).Spearman correlation analysis showed that SKL was positively correlated with eGRF and TIR(P<0.01),and negatively correlated with Scr,UACR,CysC,β2-MG,FPG,HbA1c,MG,TAR and GMI(P<0.01).Multiple linear regression analysis showed that HbA1c and GMI were the influencing factors of SKL.Conclusion The level of SKL in DKD patients is correlated with HbA1c and GMI.

Objective To analyze the status of the bacteria in the operative area of transnasal skull base surgery and its correlation with postoperative intracranial infection.Methods The procedure of transnasal skull base surgery was divided into three stages:nasal passage preparation(stage 1),tumor resection(stage 2),and skull base reconstruction(stage 3).Bacterial sampling was taken from the mucosa of the anterior wall of sphenoid sinus or clival recess of sellar floor at the beginning of each stage;and the positive rate of bacterial culture in different stages of operation and its correlation with postoperative intracranial infection were analyzed.Results A total of 105 patients were enrolled in this study,and 315 samples were taken.The average time point of sampling in the three stages was 20.3,45.1 and 131.3 min after the beginning of operation,respectively.The positive results were 9 cases(2.9％)in the stage 1,8 cases(2.5％)in the stage 2,and 23 cases(7.3％)in the stage 3,which were 24 cases of Staphylococcus epidermidis,7 cases of Staphylococcus aureus,3 cases of hemolytic streptococcus,2 cases of Klebsiella pneumonia,and 4 cases of Escherichia coli.There was no significant difference in the positive cases between stage 1 and stage 2(P=0.955),but there were significant differences between stage 1 or 2 and stage 3(P=0.013;P=0.007).There were 36(11.4％)patients with at least one positive result in the three stages,17(16.2％)with cerebrospinal fluid leakage,and 12(11.4％)with intracranial infection.The risk of intracranial infection was 3.1 times higher in patients with positive bacterial culture than patients with negative bacterial culture(OR=3.1,95％CI:0.9-10.6),which was not statistically significant;patients with CSF leakage were 61.4 times higher than those without CSF leakage(OR=61.4,95％CI:11.2-337.1),which was statistically significant(P＜0.001).The consistency rate of bacteria in nasal cavity and postoperative cerebrospinal fluid culture was 57.1％.Conclusion The positive rate of bacterial culture in the operative area of transnasal skull base surgery increases significantly with the extension of operation time,which is a potential risk index of postoperative intracranial infection.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective To evaluate the feasibility,reliability and validity of the symptom identification scale for kidney yang deficiency syndrome.Methods The symptom identification scale for kidney yang deficiency syndrome developed in previous research was administered to 200 vascular cognitive impairment patients from September 2020 to September 2022 to assess feasibility through recall rate,completion rate,and completion time;reliability was measured using retest reliability,split-half reliability,homogeneity reliability,and inter-rater reliability;and validity was evaluated based on discriminant and structural validity.Results A total of 200 scales were sent out,and all of them cooperated and were completed and retrieved within 20 min.The results of reliability analysis showed that the retest reliability of the scale was 0.828 for the dimension of yang deficiency and 0.718 for the dimension of kidney qi deficiency;the Spearman-Brown coefficient of split-half reliability was 0.784;the Cronbach coefficient of the dimension of yang deficiency was 0.799,and the Cronbach coefficient of the dimension of kidney qi deficiency in the homogeneity reliability was 0.670.The results of the analysis showed that the differences between the kidney yang deficiency syndrome group and the non-kidney yang deficiency syndrome group in the yang deficiency dimension,kidney qi deficiency dimension scores and total scale scores in the discriminant validity were statistically significant(P<0.001);the KMO value in the structural validity was 0.842,and a total of two factors with eigenvalues greater than 1 were extracted,with a cumulative variance contribution rate of 58.227%.Conclusion The symptom identification scale for kidney yang deficiency syndrome demonstrates adequate reliability and validity,potentially enhancing the prediction of kidney yang deficiency in vascular cognitive impairment.However,the validity of the scale is somewhat limited and requires further refinement for clinical application.

significantly attenuated the hyper-phosphorylation of tau proteins. These data suggested that inhibition of cdk-5 activity has neuropro-tective effect on neurons in NPC mice.