[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.

Objective To investigate the relationship between baseline aqueous humor cytokines and optical coher-ence tomography angiography(OCTA)changes in eyes with macular edema secondary to retinal vein occlusion(RVO-ME)after anti-vascular endothelial growth factor(VEGF)treatment.Methods From October 2021 to January 2023,30 eyes of 30 patients diagnosed with RVO-ME at the Affiliated Eye Hospital of Nanjing Medical University were included in this study.All eyes were treated with the intravitreal injection of anti-VEGF drugs once a month for 3 consecutive months and then treated as needed.The aqueous humors before the first and third injections were collected.The expression levels of VEGF,interleukins(IL),γ-interferon(IFN-y),intercellular adhesion molecule-1(ICAM-1),and platelet-derived growth factor(PDGF)were detected using the Luminex platform.The central macular thickness(CMT),fovea avascular zone(FAZ)area,perimeter(PERIM),acircularity index(AI),and the vessel density in a 300 μm wide region around FAZ(FD-300)were measured using OCTA.The best corrected visual acuity(BCVA)was examined using the international standard logarithmic visual acuity chart,which was converted into the logarithm of the minimum angle of resolution(log-MAR)for statistics.Aqueous humor cytokines and OCTA parameters were compared before and after anti-VEGF treatment for RVO-ME,and the relationship between OCTA changes(the difference between before and after treatment)and baseline aqueous humor cytokines was analyzed.Results After treatment,the levels of VEGF,ICAM-1,PDGF,IL-8,and IL-10 in RVO-ME patients decreased(all P＜0.05),the BCVA improved(P＜0.001),and CMT,AI and FD-300 decreased(all P＜0.05).Correlation analysis results showed that baseline IL-13 was negatively correlated with the AI change(r=-0.388,P＜0.05),and baseline IL-8 was negatively correlated with the FD-300 change(r=-0.421,P＜0.05).Conclusion Baseline IL-13 and IL-8 may be related to the improvement of the retinal macular microvascular structure after anti-VEGF treatment for RVO-ME.For the treatment and management of RVO-ME,in addition to anti-VEGF therapy,targeted anti-in-flammatory therapy should also be considered.

Objective To analyze the effect of baseline cytokines in aqueous humor in predicting the improvement of the central macular thickness(CMT)and best corrected visual acuity(BCVA)of patients with macular edema secondary to retinal vein obstruction(RVO-ME)after anti-vascular endothelial growth factor(VEGF)treatment for 3 months.Meth-ods Totally 30 eyes of 30 patients initially diagnosed with RVO-ME in the Affiliated Eye Hospital of Nanjing Medical Uni-versity from October 2021 to January 2023 were enrolled.Aqueous humor was collected by anterior chamber puncture be-fore the anti-VEGF drug injection.The levels of 11 cytokines in aqueous humor,including VEGF,intercellular adhesion molecule(ICAM)-1,interleukins(ILs)and interferon-γ(IFN-γ),were measured by Luminex xMAP technology.The cor-relation between baseline aqueous humor cytokine levels and CMT,BCVA(logMAR)as well as their changes(difference between baseline and anti-VEGF treatment for 3 months)in RVO-ME patients was analyzed;the correlation between CMT and BCVA(logMAR)was analyzed at baseline and 3 months after anti-VEGF treatment.CMT and BCVA responders were defined as patients with 50％or more reduction in CMT and BCVA(logMAR)from baseline to the third month.A Logistic regression model was used to analyze the relationship between baseline aqueous humor cytokines and RVO-ME patients be-coming CMT or BCVA responders after 3 months of anti-VEGF treatment.Results Compared with baseline,the CMT sig-nificantly decreased and BCVA significantly improved in RVO-ME patients after anti-VEGF treatment for 3 months(both P＜0.001).The CMT was positively correlated with BCVA(logMAR)of RVO-ME patients at baseline and after anti-VEGF treatment for 3 months(P=0.026,0.002).At baseline,the levels of VEGF and IL-8 of RVO-ME patients were positively correlated with CMT(P=0.032,0.035);the levels of IL-6 and IL-8 were positively correlated with BCVA(logMAR)(P=0.018,0.002).The baseline IL-8 level in RVO-ME patients was negatively associated with the change in CMT(P=0.024).Logistic regression analysis showed that elevated baseline ICAM-1 level could increase the risk of RVO-ME patients becom-ing BCVA non-responders after 3 months of anti-VEGF treatment(P=0.023).Conclusion Baseline IL-8 and ICAM-1 may be predictors of CMT and BCVA improvement after anti-VEGF treatment of RVO-ME.

Objective To investigate the relationship between intracranial arterial calcification and prognosis after mechanical thrombectomy in patients with acute large vessel occlusion stroke. Methods A total of 147 patients with acute large vessel occlusion stroke who underwent mechanical thrombectomy were enrolled in this study. The length, density, and location of intracranial arterial calcification were evaluated by CT. Based on the intracranial arterial calcification status, patients were divided into three groups: symptomatic intracranial arterial calcification group (n=42), asymptomatic intracranial arterial calcification group (n=24), and no intracranial arterial calcification group (n=81). Multivariate Logistic regression analysis was performed to explore the relationship between intracranial arterial calcification and clinical outcomes after mechanical thrombectomy. Results Compared with patients in the asymptomatic and no intracranial arterial calcification groups, patients in the symptomatic intracranial arterial calcification group, had older age, a higher proportion of hypertension, and required more rescue angioplasty or stenting after mechanical thrombectomy (P < 0.05). There was a statistically significant difference in the location of calcification between the symptomatic and asymptomatic intracranial arterial calcification groups (P < 0.05), but no significant differences in the length and density of calcification between the two groups were observed (P>0.05). Multivariate Logistic regression analysis revealed that symptomatic intracranial arterial calcification was an independent risk factor for failed revascularization (adjusted OR=8.67, 95%CI, 2.39 to 15.68, P < 0.001), the need for rescue interventional therapy (adjusted OR=6.46, 95%CI, 2.26 to 14.29, P < 0.001), and poor neurological recovery (adjusted OR=3.91, 95%CI, 1.38 to 10.16, P=0.023) after adjusting for potential confounding factors. Conclusion Symptomatic intracranial arterial calcification is closely associated with poor clinical outcomes after mechanical thrombectomy in patients with acute large vessel occlusion stroke. Preoperative assessment of intracranial arterial calcification is crucial for selecting revascularization strategies in these patients.

Objective:To compare the changes in functional optical zone (FOZ) and corneal morphology in myopes between femtosecond small incision laser lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK).Methods:A cohort study was performed.A total of 94 patients (94 eyes) who underwent FS-LASIK or SMILE at Eye Hospital, Wenzhou Medical University from March to December 2021 were enrolled.The selected patients were divided into a SMILE group (46 cases, 46 eyes) and an FS-LASIK group (48 cases, 48 eyes) according to the surgical procedure, and the follow-up period was 6 months.The primary outcome measures were postoperative changes in corneal FOZ and Q-value, and the secondary outcome measures were changes in central corneal thickness (CCT) and mean corneal curvature (Km). Corneal Q-value, horizontal and vertical FOZ diameters, CCT, and Km were recorded before surgery and at 1 day, 1 week, 1 month, and 6 months after surgery using the Pentacam anterior segment analysis system, and the differences in each parameter and the trends of changes between the two groups were compared.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Eye Hospital, Wenzhou Medical University (No.2021-034-k-27). Written informed consent was obtained from each subject.Results:There were statistically significant overall differences in the postoperative horizontal and vertical FOZ diameters between the two groups (horizontal diameter: Fgroup=7.06, P<0.001; Ftime=64.18, P=0.001; vertical diameter: Fgroup=11.08, P<0.001; Ftime=77.14, P<0.001). The horizontal and vertical FOZ diameters were significantly larger in SMILE group than in FS-LASIK group at various postoperative time points, and the differences were statistically significant (all at P<0.001). In the two groups, the postoperative 1-week, 1-month and 6-month horizontal FOZ diameters and the postoperative 1-week and 1-month vertical FOZ diameters were smaller than the postoperative 1-day ones, and the differences were statistically significant (all at P<0.05). There were significant overall differences in Q-values at different postoperative time points between the two groups ( Fgrouup=53.11, P=0.019; Ftime=29.18, P<0.001). The postoperative 1-day, 1-week, and 1-month Q-values of FS-LASIK group were significantly higher than those of SMILE group (all at P<0.05). The postoperative 1-week Q-value was significantly larger than the postoperative 1-day value in SMILE group ( P<0.001). The postoperative Q-values gradually decreased with time in FS-LASIK group, with significant pairwise differences at all adjacent time points (all at P<0.001). There were significant differences in CCT at various postoperative time points between the two groups ( Ftime=21.43, P<0.01). In FS-LASIK group, the CCT was decreased at 1 week than 1 day after surgery and was increased at 6 months than 1 week after surgery, and the differences were statistically significant (all at P<0.05). In SMILE group, the postoperative 1-week, 1-month and 6-month CCT was increased in comparison with the postoperative 1-day value, and the differences were statistically significant (all at P<0.05). There was no significant overall difference in the Km between the two groups ( Fgroup=27.29, P=0.41). There were significant pairwise differences in the Km at different postoperative time points between the two groups (all at P<0.001). The postoperative 6-month Km was smaller than the postoperative 1-day value in SMILE group, and the postoperative 6-month Km was greater than the postoperative 1-day value in FS-LASIK group (both at P<0.05). Conclusions:The FOZ shows a trend of gradual reduction within a month after SMILE and FS-LASIK.The FOZ is larger after SMILE than after FS-LASIK.The morphologic stability of corneal FOZ is better after SMILE than after FS-LASIK.

The endocrown, a modified overlay or crown, is considered to have the advantages of adhesive retention and mechanical retention. Marginal adaptation and mechanical strength are common criteria for evaluating endocrowns. This review studied these aspects of endocrowns to guide further clinical application. Results from previous academic studies indicate that endocrowns made of different materials, such as glass-based ceramics, zirconia-based ceramics and resin-based ceramics, exhibit clinically acceptable marginal adaptation. Zirconia is a common dental material, but when used in endocrowns, it tends to present a risk of irreparable tooth root fractures. Compared with products manufactured with zirconia, endocrowns manufactured with resin-based ceramics and glass-based ceramics, such as lithium disilicate ceramics, do not tend to cause irreparable results, such as tooth root fracture, but their mechanical strengths are not as good as those of zirconia. At the same time, the tooth prepration design such as the types of endocrowns, the pulp chamber extension depth and angles, the endocrown thickness can influence the mechanical strength of endocrowns as well. Compared with traditional zirconia, self-glazed zirconia, a new type of material used to restore defective teeth, has the similar elasticity modulus（210 GPa）and better aesthetic advantages, and is suitable for short crown patients with insufficient occlusal space. Further study is warranted to improve the performance of endocrowns made from ceramic materials to prevent root fracture.

Occupational therapy can not only promote the development of motor and cognitive functions in children with developmental or other disabilities, but also improve their self-care ability, learning ability, participation skills and other activities.In 2019, the Aust Occup Ther J published a systematic review on the effects of occupational therapy interventions on disabled children, aiming to summarize the best evidence of occupational therapy and help occupational therapists and families to choose the effective treatment regimens.In this article, the systematic review was interpreted in light of the current status of domestic child occupational therapy, so as to allow clinicians to compare the pros and cons of different treatment methods and improve the efficacy.

OBJECTIVE: To explore the effects of aerobic exercise combined with huwentoxin-I (HWTX-I)-mediated Keap1-Nrf2-ARE pathway on phase II detoxification enzymes HO-1 and NQO1 and their protective effects against obstructive jaundice (OJ)-induced central nervous system injury in mice. METHODS: 50 male KM mice were randomly divided into blank group (GO), model group (M), aerobic exercise group (T), HWTX-I group (H), and aerobic exercise combined with HWTX-I group (TH). Mouse models of OJ were established with surgical suture for 72 h in the mice in all the groups except for the blank control group. The mice received interventions by aerobic exercise and tail vein injection of HWTX-I (0.05 μg/g) and were assessed by behavioral observation, Clark's neurological function scores, enzyme-linked immunosorbent assay (ELISA), brain tissue Nissl staining, hippocampal tissue Western blotting, and liver tissue mRNA expression profiling and sequencing. RESULTS: The mice in group M had obvious jaundice symptoms after the operation with significantly increased Clark's neurological score ( < 0.01). Compared with those in group M, the mice in group T, group H, and group TH showed significantly decreased serum levels of ALT, AST, TBIL, and TBA ( < 0.01) with increased contents of 5-HT and BDNF and decreased contents of S100B and NSE in the hippocampus ( < 0.01). Synergistic effects between aerobic exercise and HWTX-I were noted on the above parameters except for the liver function indicators. Interventions with aerobic exercise and HWTX-I, alone or in combination, obviously lessened pathologies in the brain tissue induced by OJ, and the combined treatment produced the strongest effect. The treatment also increased the expression levels of Nrf2, HO-1, and NQO1 mRNA and protein in brain tissues ( < 0.01 or 0.05) with a synergistic effect between aerobic exercise and HWTX-I. Illumina high-throughput sequencing showed that the differentially expressed factors participated mainly in such neural regulatory pathways as neuroactive ligand-receptor interaction, GABAergic synapses, dopaminergic synapses, synaptic vesicle circulation, and axon guidance, involving tissue cell neuronal signal transduction, apoptosis inhibition, immune response, and toxicity. Aerobic exercise and HWTX-I synergistically increased the accumulation of the signal pathways related with neuron damage repair and proliferation. CONCLUSIONS Aerobic exercise combined with HWTX-I can up-regulate the expression of phase Ⅱ detoxification enzymes HO-1 and NQO1 through the Keap1-Nrf2-ARE pathway to protect the central nervous system against OJ-induced damage in mice.
Animals ; Jaundice, Obstructive ; Kelch-Like ECH-Associated Protein 1 ; Male ; Metabolic Detoxication, Phase II ; Mice ; NF-E2-Related Factor 2 ; Physical Conditioning, Animal ; Reptilian Proteins ; Spider Venoms ; Trauma, Nervous System

Objective:To investigate the early predictive value of lupus anticoagulant (LA) ratio, D-dimer (D-D) and soluble endothelial protein C receptor (sEPCR) on deep vein thrombosis (DVT).Methods:Thirty hundred and fifty patients who performed surgery for lower extremity fracture and suspected DVT in Zhejiang Rongjun Hospital from October 2018 to October 2019 were enrolled. With deep vein contrast of the lower extremity as the gold standard, 82 patients with confirmed DVT were treated as the observation group and 268 patients without DVT as the control group. The levels of LA, D-D and sEPCR of two groups were detected by coagulation, immunoturbidimetry and enzyme linked immunosorbent assay—sandwich technique respectively. Indexes of the two groups were compared. Pearson correlation was used to analyze the relationship between plasma levels of LA, D-D and sEPCR, and the predictive value of plasma sEPCR, LA ratio and D-D level on DVT was evaluated by receiver operator characteristic (ROC) curve.Results:The plasma sEPCR, LA ratio and D-D levels in the observation group were significantly higher than those in the control group [(143.30 ± 11.28) μg/L vs.(112.56 ± 14.62) μg/L, 1.51 ± 0.24 vs. 1.22 ± 0.18, (1 013.00 ± 319.54) μg/L vs. (425.17 ± 100.36) μg/L] with statistically significant differences ( P < 0.05). There was no significant differences in activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) between the two groups ( P > 0.05). In the observation group, plasma sEPCR level was positively correlated with LA ratio and D-D level ( r = 0.280, P = 0.011; r = 0.563, P < 0.001), and LA ratio was positively correlated with D-D level( r = 0.741, P < 0.001). The area under curve (AUC) of D-D in diagnosis of DVT was 0.940, and the sensitivity and specificity were 87.80% and 87.69% when the cut-off value was 569.43 μg/L. The AUC of LA ratio in the diagnosis of DVT was the smallest, which was 0.912, the sensitivity and specificity were 87.80% and 91.25% when the cut-off value was 1.23. The sensitivity was 95.12% and specificity was 95.00% of sEPCR and LA ratio combined with DD in diagnosis of DVT. Conclusions:LA and D-D combined with sEPCR has high predictive value for DVT.

Objective To investigate the expression and the relationship with angiogenesis of miR-195 and NLR family member X1 (NLRX1) in granulation tissue after negative-pressure wound treatment (NPWT).Methods Six patients were collected who received negative pressure treatment with refractory wound granulation.The levels of miR-195, NLRX1 mRNA and NLRX1 proteins were measured.The expression of NLRX1 and the micro-vascular density (MVD) of CD31 were detected by immunohistochemistry (IHC).Results MiR-195 and MVD were significantly higher in granulation tissue after 7 days negative pressure treatment (P＜0.05), and NLRX1 was significantly lower (P ＜0.05).In granulation tissue,the expression of miR-195 was negatively correlated with NLRX1 (r =-0.856, P ＜0.001), the expression of NLRX1 was negatively correlated with MVD (r =-0.618, P ＜0.05), and the expression of miR-195 was positively correlated with MVD (r =0.630, P ＜ 0.05).Conclusions Negative pressure wound therapy can promote the formation of granulation vessels and the wound healing.The therapeutic mechanism may inhibit the expression of NLRX1 and upregulate the expression of miR-195 to promote angiogenesis.