BACKGROUND:The composite hydrogel scaffold formed by crosslinking of gelatin-methacryloyl(Gel-MA)and treated dentin matrix(TDM)under a certain proportion of ultraviolet light has good porosity,mechanical properties,swelling properties,and biodegradation rate,which provides a new idea and method for clinical pulp regeneration of young permanent teeth. OBJECTIVE:To explore the effect of Gel-MA/TDM composite hydrogel scaffold with 1:2 mass ratio on the proliferation ability and osteogenic/odontoblast differentiation ability of human dental pulp stem cells. METHODS:The passage 3 dental pulp stem cells were inoculated into the Gel-MA/TDM composite hydrogel scaffold with a mass ratio of 1:2.The proliferation ability of human dental pulp stem cells in the composite hydrogel scaffold was detected by CCK-8 assay.Dental pulp stem cells at passage 3 were cultured in Gel-MA/TDM composite hydrogel scaffold with a mass ratio of 1:2 for osteogenic induction.The formation of mineralized nodules was observed by alkaline phosphatase and alizarin red staining.The gene expression levels of odontogenic factors(dentin matrix protein 1,dentin sialophosphoprotein),and osteogenic factors(osteocalcin,Runt-related transcription factor 2)were detected by RT-PCR. RESULTS AND CONCLUSION:(1)The results of CCK-8 assay showed that the proliferation ability of dental pulp stem cells increased significantly in the first 7 days,and slowed down on day 10.(2)The results of alkaline phosphatase staining and alizarin red staining showed that the alkaline phosphatase activity and the formation of mineralized nodules of dental pulp stem cells in the Gel-MA/TDM composite hydrogel group were stronger than those in Gel-MA hydrogel group(P<0.05).(3)RT-PCR results showed that the gene expression levels of dentin matrix protein 1,dentin sialophosphoprotein,osteocalcin,and Runt-related transcription factor 2 in dental pulp stem cells in Gel-MA/TDM composite hydrogel group were significantly higher than those in Gel-MA hydrogel group(P<0.05).The gene expression level at 14 days was significantly higher than that at 7 days(P<0.05).The results conclude that the dental pulp stem cells cultured on Gel-MA/TDM composite hydrogel scaffolds with a mass ratio of 1:2 exhibit a good proliferation ability,which can strengthen the osteogenic and odontogenic differentiation abilities of dental pulp stem cells.

Fractals refer to structures whose component parts exhibit similarity to the whole in certain aspects. The retinal microvascular system, as the only terminal microvasculature that can be directly observed in vivo, possesses a tree-like branching morphology that conforms to the characteristics of fractals. Fractal dimension(FD)is a numerical value that describes the density and complexity of the overall retinal vascular network, complementing the limitations of vessel density alone in characterizing vascular structural features. In recent years, the widespread application of optical coherence tomography angiography(OCTA)has enabled the visualization of blood flow across various retinal capillary layers, thereby extending the concept of fractal analysis to the retinal microvasculature. FD has been demonstrated to serve as a novel potential biomarker for ophthalmic conditions, including diabetic retinopathy, glaucoma, age-related macular degeneration, high myopia, and retinal vein occlusion, providing valuable metrics for the early diagnosis of these diseases. This review provides a comprehensive summary of the definition, calculation methods, influencing factors, and recent research developments regarding FD in various ophthalmic disorders.

AIM: To explore the clinical application effect of visual training equipment combined with conventional corrective treatment on children with ametropic amblyopia(AMA).METHODS: Prospective randomized control study. A total of 188 children(376 eyes)with AMA treated in our hospital from June 2021 to December 2022 were selected, and they were divided into two groups using a random number table. The conventional correction group(94 cases, 188 eyes)received conventional correction treatment, while the visual training group(94 cases, 188 eyes)received visual training equipment combined with conventional correction treatment, both lasted for 12 mo. The best corrected visual acuity, diopter, eye accommodation function, adverse reactions, amblyopia recurrence rates, and clinical efficacy were compared between the two groups at 6 and 12 mo after treatment.RESULTS:The two groups each had 8 cases(16 eyes)detached, the rate of loss to follow-up was 8.5%, and 86 cases(172 eyes)were included in each group. There were statistically significant differences in the best corrected visual acuity, diopter, amplitude of accommodation, accommodation facility and accommodative lag between the two groups of children before and after treatment(all P<0.05). The total effective rate of the visual training group(98.8%)was higher than that of the conventional correction group(91.9%; P<0.05). There was no statistically significant difference in the total effective rate of clinical efficacy between the two groups in different age groups and different degrees of amblyopia(all P>0.05). There was no statistically significant difference in the incidence of redness and swelling between the two groups(P>0.05). The recurrence rate of amblyopia in the visual training group(1.2%)was lower than that in the conventional correction group(8.1%; P<0.05).CONCLUSION: The combination of visual training equipment and conventional correction therapy has a significant clinical effect on children with AMA, which can effectively correct visual acuity, adjusting diopter and improve eye accommodation function, and recurrence rate of amblyopia is low and safety is high.

BACKGROUND:Pulp regeneration has been a hot and difficult research topic in recent years,and the construction of composite bio-scaffolding materials provides new ideas and methods for pulp regeneration. OBJECTIVE:To observe the effect of freeze-dried gelatin modified by methacrylic anhydride/treated dentin matrix bioactive scaffolds on proliferation,migration,and osteogenic differentiation of human dental pulp stem cells. METHODS:The mass ratios of gelatin modified by methacrylic anhydride and treated dentin matrix at 2:1,1:1 and 1:2 were obtained by dispersing different masses of treated dentin matrix into gelatin modified by methacrylic anhydride solution.The gelatin modified by methacrylic anhydride/treated dentin matrix bioactive scaffolds were prepared by vacuum freeze-drying.The microstructure,water absorption,and mechanical properties of the scaffolds were measured.Human dental pulp stem cells were cultured with different mass ratios of scaffold extract and DMEM(control group)to detect cell proliferation and migration.Human dental pulp stem cells were cultured with different mass ratios of scaffold extract + osteogenic induction solution and DMEM + osteogenic induction solution(control group),and their osteogenic ability was analyzed by alkaline phosphatase staining. RESULTS AND CONCLUSION:(1)Under scanning electron microscopy,the scaffolds of the three groups all had porous structures.The porosity of the scaffolds increased with the increase of treated dentin matrix quality,and there was significant difference between the two groups(P＜0.05).The water absorption of scaffolds increased with the increase of treated dentin matrix mass,and there was significant difference between groups(P＜0.05).The compressive strength and shear strength of the scaffold increased with the increase of the mass of treated dentin matrix.(2)CCK-8 assay showed that after 3,5,and 7 days of culture,the cell proliferation absorbance values in the 2:1,1:1,and 1:2 scaffold groups were higher than those in the control group(P＜0.05).The cell proliferation absorbance values increased with the increase of treated dentin matrix mass in the scaffold(P＜0.05).The cell scratch test showed that the cell migration rate in the 2:1,1:1,and 1:2 scaffold groups was higher than that in the control group(P＜0.05),and the cell migration rate increased with the increase of treated dentin matrix mass in the scaffold(P＜0.05).(3)Alkaline phosphatase staining showed that the osteogenic differentiation ability of cells in the 2:1,1:1,and 1:2 scaffold groups was stronger than that in the control group,and the osteogenic ability of cells was enhanced with the increase of treated dentin matrix mass in the scaffold.(4)The results showed that the scaffold with a mass ratio of 1:2 between gelatin modified by methacrylic anhydride and treated dentin matrix was the most suitable for the proliferation and differentiation of dental pulp stem cells.

Objective To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.Methods NIH-3T3 cells were treated with quercetin or MCC950(a specific inhibitor of NLRP3)before stimulation with lipopolysaccharide(LPS)and ATP to induce cell pyroptosis.The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times.Morphological changes of the treated cells was observed,and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA;the protein expressions of NLRP3,cleaved caspase-1,and GSDMD-N and the mRNA levels of NLRP3,caspase-1 and GSDMD were detected using Western blotting and qRT-PCR.The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay.Results The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results.LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling,cell membrane rupture and leakage of cell contents,significantly increased IL-18 and IL-1β levels,and enhanced protein expressions of NLRP3,cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3,caspase-1 and GSDMD.LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells.Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP,lowered the concentrations of IL-18 and IL-1β,decreased the expression levels of NLRP3,caspase-1/cleaved caspase-1,GSDMD/GSDMD-N,and reduced the number of TUNEL-positive cells and LDH release.Conclusion Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Objective To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.Methods NIH-3T3 cells were treated with quercetin or MCC950(a specific inhibitor of NLRP3)before stimulation with lipopolysaccharide(LPS)and ATP to induce cell pyroptosis.The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times.Morphological changes of the treated cells was observed,and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA;the protein expressions of NLRP3,cleaved caspase-1,and GSDMD-N and the mRNA levels of NLRP3,caspase-1 and GSDMD were detected using Western blotting and qRT-PCR.The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay.Results The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results.LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling,cell membrane rupture and leakage of cell contents,significantly increased IL-18 and IL-1β levels,and enhanced protein expressions of NLRP3,cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3,caspase-1 and GSDMD.LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells.Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP,lowered the concentrations of IL-18 and IL-1β,decreased the expression levels of NLRP3,caspase-1/cleaved caspase-1,GSDMD/GSDMD-N,and reduced the number of TUNEL-positive cells and LDH release.Conclusion Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Objective To observe the value of MR lymphangiography(MRL)radiomics for evaluating central conducting lymphatic anomaly(CCLA).Methods Sixty-one patients with complex lymphatic anomaly,including 41 CCLA(group A),20 non-CCLA(generalized lymphatic anomaly and Gorham-Stout disease)and 20 subjects with normal thoracic duct(group B,n=38)were retrospectively enrolled.Cervical and thoracic(combined with abdominal if necessary)MRL was acquired using three-dimensional heavily T2W fast spin echo sequence.ROI was delineated along overall thoracic duct,and radiomics features were extracted.Data sets of group A and B were divided into K subsets using 5-fold cross-validation.The union of(K-1)subset was always used as training set,while the other subsets were used as validation set.Radiomics model was constructed based on support vector machine(SVM)algorithm.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of SVM model for assessing CCLA.Results The proportions of bifurcation,cystoid change and extension of main thoracic duct,and extension of terminal thoracic duct in group A were all higher,while of normal main and terminal thoracic duct in group A were both lower than those in group B(all P＜0.05).No significant difference of proportions of multiple thoracic ducts,dextral thoracic duct,part of thoracic duct invisible,multiple terminal thoracic ducts,cystoid change of terminal thoracic duct nor terminal thoracic duct pampiniform was found between groups(all P＞0.05).The sensitivity,specificity,accuracy,positive predictive,negative predictive and AUC of SVM model for evaluating CCLA in training set was 78.95％,97.56％,88.61％,96.77％,83.33％and 0.920,respectively,which in validation set was 78.95％,83.57％,82.28％,83.33％,81.40％and 0.833,respectively.Conclusion MRL radiomics could be used to effectively evaluate CCLA.

Objective:To investigate the neuroprotective effect of synthetic triterpenoid(CDDO-Im)on ischemic stroke rats and its influence on inflammatory response by activating the nuclear factor 2-related factor 2(Nrf2)/antioxidant response elements(ARE)signaling pathway.Methods:SD rats were divided into sham group(S group),MCAO group(M group)and CDDO-Im inter-vention group(M+C group).The middle cerebral artery occlusion(MCAO)was used in M group and M+C group to establish ischemic stroke model in rats,and sham operation was used in S group to control.After operation,M+C group was injected with CDDO-Im(64 μg/300 g)every12 hours via caudal vein,S group and M group were given the same amount of normal saline.After 3 days,the nerve function of rats was measured by Longa score,and the area of cerebral infarction was evaluated by 2,3,5-triphenyltetrazolium chlo-ride(TTC)staining.The expressions of Nrf2,heme oxygenated-1(HO-1),ionic calcium binding adaptor molecule 1(Iba1),IL-1β and IL-4 protein were detected by Western blot.Results:Compared with S group,M group rats showed significant neurologic deficit and cerebral infarction area,and the expression of Nrf2 protein had no significant difference,and the expression levels of HO-1,Iba1,IL-1β and IL-4 protein were increased significantly(P<0.05).Compared with M group,the neurological deficit score,cerebral infarction area,the expression levels of Iba1 and IL-1β protein were decreased significantly(P<0.05),while Nrf2,HO-1 and IL-4 pro-tein expression increased significantly in M+C group(P<0.05).Conclusion:CDDO-Im may activate the Nrf2/ARE signaling pathway and play a neuroprotective role,which may be related to the modulation of microglia to M2 and the regulation of inflammatory response.

BACKGROUND: Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients. METHODS: A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO. RESULTS: Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 μmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05). CONCLUSION Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.
Humans ; Middle Aged ; Gallbladder Neoplasms/pathology* ; Retrospective Studies ; Prognosis ; Hepatectomy ; Cholecystectomy

Objective To construct a Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model by crossbreeding Pnpla3 148M/M homozygous mice and Tm6sf2 167K/K homozygous mice. Methods Pnpla3 148I/M Tm6sf2 167E/K heterozygous mice were bred by hybridization of Pnpla3 148M/M Tm6sf2 167E/E and Pnpla3 148I/I Tm6sf2 167K/K homozygous mice, and the Pnpla3 148M/M Tm6sf2 167K/K mice were obtained by the self-crossbreeding of Pnpla3 148I/M Tm6sf2 167E/K mice. Male mice of Pnpla3 148M/M Tm6sf2 167K/K ( n =6), Pnpla3 148M/M Tm6sf2 167E/E ( n =6), and Pnpla3 148I/I Tm6sf2 167K/K ( n =6) genotypes and Wt mice ( n =6) were fed with normal diet for 8 weeks, and then the glucose and lipid metabolism indices were measured. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison bewteen two groups. Results Agarose gel electrophoresis and nucleic acid sequencing results showed that the Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model was successfully constructed. There were no significant difference in body weight between the Pnpla3 148M/M Tm6sf2 167K/K mice and the Pnpla3 148M/M Tm6sf2 167E/E , Pnpla3 148I/I Tm6sf2 167K/K , and Wt mice (all P > 0.05). The Pnpla3 148M/M Tm6sf2 167K/K mice had a significantly higher liver wet weight than the Wt mice ( P < 0.05). The fasting blood glucose of Pnpla3 148M/M Tm6sf2 167K/K mice was significantly lower than that of Pnpla3 148I/I Tm6sf2 167K/K mice and Wt mice (both P < 0.05). The glucose tolerance of Pnpla3 148M/M Tm6sf2 167K/K mice was significantly reduced compared with the Pnpla3 148I/I Tm6sf2 167K/K mice ( P < 0.05). There were no significant differences in insulin level between the four groups of mice (all P > 0.05). Also, there were no significant differences in the serum levels of biochemical indices between the Pnpla3 148M/M Tm6sf2 167K/K mice and the Pnpla3 148M/M Tm6sf2 167E/E , Pnpla3 148I/I Tm6sf2 167K/K , and Wt mice (all P > 0.05). Oil red O staining of the liver showed that more lipid accumulation was observed in the Pnpla3 148M/M Tm6sf2 167K/K mice than in the Pnpla3 148M/M Tm6sf2 167E/E and Wt mice. Conclusion The Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model was successfully constructed. Pnpla3 Ⅰ 148M and Tm6sf2 E 167K double mutations can cause abnormal glucose metabolism in mice.