Objective To investigate the mechanism of Naringenin(NGN)in the treatment of steroid(glucosteroid)-induced osteonecrosis of the femoral head(SONFH).Methods A SONFH rat model was established using Methylprednisolone(MPS)treatment,followed by intervention with NGN and zinc protoporphyrin(ZnPP).Micro-CT was used to analyze the morphological changes in femoral head tissues,and the levels of osteocalcin(OCN)in rat serum as well as heme oxygenase-1(HO-1)and hypoxia-inducible factor-1α(HIF-1α)in femoral bone tissue were measured.A cellular model was constructed by treating MC3T3-E1 cells with Dexamethasone(DEX),followed by NGN intervention.Bioinformatics analysis combined with molecular docking technology was used to predict the target of NGN,and the Pulldown experiment was performed for validation.The expression of HO-1 was knocked down through cell transfection,to analyze the viability,proliferation,apoptosis,and migration of MC3T3-E1 cells,and angiogenesis assays were conducted to evaluate the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Results Micro-CT analysis revealed that,compared with the control group,the trabecular thickness and trabecular number were significantly reduced in the MPS group,while the bone surface area/bone volume ratio and trabecular separation were significantly increased(P<0.001).In vitro experimental results indicated that DEX inhibited the proliferation of MC3T3-E1 cells,promoted cell apoptosis,and increased reactive oxygen species generation(P<0.01),and that DEX suppressed the formation of mineralized nodules,a key indicator of osteogenic differentiation,and downregulated the expression of osteogenesis-related genes(Runt-related transcription factor 2,osteopontin,osteocalcin)(P<0.01).However,NGN treatment partially reversed these effects.DEX significantly inhibited the migration of HUVECs,angiogenesis,and the expression of angiogenesis-related markers(platelet endothelial cell adhesion molecule-1,vascular endothelial growth factor,and von Willebrand factor)(P<0.01).In contrast,NGN treatment did not significantly affect the aforementioned effects,but the treatment with NGN conditioned medium[CM(NGN)]partially reversed these effects(P<0.01).Bioinformatics analysis combined with Pulldown assay results indicated that HO-1 was the target of NGN.DEX treatment significantly downregulated the expression of HO-1,while NGN intervention partially counteracted the inhibitory effect induced by DEX(P<0.01);knockdown of HO-1 negated the therapeutic effects of NGN(P<0.01).Compared with MPS administration alone,the combined administration of NGN and MPS upregulated the expression of HO-1 and HIF-1α in rat femoral head tissues.However,the HO-1 inhibitor ZnPP further upregulated the expression of HO-1 but downregulated the protein level of hypoxia-inducible factor-α(HIF-1α)(P<0.01).Conclusion NGN exerts its therapeutic effects on SONFH by activating the expression and activity of HO-1,which regulates the HIF-1α/VEGF pathway to promote osteoblast differentiation,bone formation,and angiogenesis.

Objective To observe the effectiveness and safety of DiaSphere embolized microsphere TACE for treating primary hepatocellular carcinoma(HCC).Methods Totally 188 patients with HCC were prospectively enrolled and randomly assigned to research group(n=93)and control group(n=95),who underwent TACE with DiaSphere embolized microspheres and Embosphere embolized microspheres,respectively.The incidence of TACE-related adverse events were recorded.The therapeutic efficacy 1 month after the first TACE,also 1 and 3 months after the last TACE,and liver functions 1 month after the first and last TACE were compared between groups.Results In research group,there were 69 cases underwent 1 time TACE,22 cases underwent 2 times and 2 cases underwent 3 times TACE,while in control group,there were 82 cases underwent 1 time and 13 cases underwent 2 times TACE,respectively.No statistical difference of the incidence of adverse events was found between groups(77.42%[72/93]vs.76.84%[73/95],P=1.000).One month after the first TACE,7 cases in research group and 11 cases in control group were lost to follow-up,respectively.One month after the last TACE,12 cases were lost to follow-up in both groups,and 3 months after the last TACE,28 cases were lost to follow-up in both groups.No significant difference of objective response rate nor disease control rate was found between groups at the above time points(all P＞0.05).One month after the first and last TACE,liver function indicators were not different between groups(all P＞0.05).Conclusion Both the short-term efficacy and safety of TACE with DiaSphere embolized microspheres for treating HCC were good.

Coronary CT angiography(CCTA)plays an important role in study of coronary atherosclerotic plaques,which can be used to assess plaque composition and vulnerability,hence predicting major adverse cardiovascular events.Furthermore,CCTA combined with radiomics analysis is helpful for optimizing cardiovascular risk stratification.The research progresses in CCTA of coronary atherosclerotic plaques were reviewed in this article.

This study was aimed at preliminarily investigating the molecular biological functions of the PPE65 protein from Myco-bacterium tuberculosis,and providing foundational data for tuberculosis prevention and control.The basic biological properties of the PPE65 gene-encoded protein were predicted with bioinformatics tools.Sequence information for the Mycobacterium tuberculosis Rv3621c gene and PPE65 protein was retrieved from the NCBI database.The Rv3621c gene was amplified through PCR with the H37Rv genome as a template,then cloned into the pET22b(+)expression vector.The recombinant pET22b(+)-PPE65 plasmid was transformed into Escherichia coli BL21(DE3)competent cells for IPTG-induced expression.Solubility analysis,purification,and identification of the recombinant PPE65 protein were performed.BEAS-2B cells were treated with various concentrations of PPE65 protein for 24 h,and cell proliferation was assessed with CCK-8 assays.PPE65 was found to be composed of 413 amino acids and to have a molecular formula of C????H????N???O???S??,a relative molecular mass of 40 679.88,a theoretical isoelectric point of 4.60,an ali-phatic index of 81.94,and an average hydrophilicity value of 0.319,thus indicating a stable hydrophobic protein lacking signal pep-tides or transmembrane domains.Secondary structure analysis revealed 53.03%α-helix(Hh),2.66%β-sheet(Ee),and 44.31%ran-dom coil(Cc).Bioinformatics predictions identified 38 B-cell epitopes and 22 CTL/Th-cell epitopes.The full-length PPE65 gene(1 308 bp)was confirmed through double restriction enzyme digestion and sequencing,thereby validating the correct construction of the pET22b(+)-PPE65 recombinant plasmid.SDS-PAGE analysis demonstrated that the recombinant protein was found in inclusion bodies,and a single band at 43.7 kDa was observed after purification.Western blotting revealed specific binding to mouse-derived His monoclonal antibodies,thereby confirming successful expression of the PPE65 protein.BEAS-2B cells treated with a PPE65 protein concentration gradient(2.5-20 μg/mL)exhibited a dose-dependent increase in cell number.Compared with those in the PBS control group,TGF-β relative expression levels were significantly higher in all treatment groups(t2.5=4.893,P<0.001,t5.0=4.640,P<0.05,t10=7.535,P<0.05,t20=16.44,P<0.000 1).This study elucidated the structural characteristics of the PPE65 protein,successfully obtained the recombinant protein through prokaryotic expression and purification,and demonstrated its ability to promote BEAS-2B cell proliferation.The underlying mechanism might involve suppression of TGF-β/S mad signaling pathway activation.These findings provide a theoretical basis for understanding the role and regulatory mechanisms of PPE65 during M.tuberculosis infection.

Objective To explore the efficacy of a model combining clinicopathological characteristics and multiparametric MRI features for predicting BRCA-mutated breast cancer(BC).Methods A total of 256 BC patients were retrospectively selected and divided into BRCA mutation group(116 cases)and BRCA wild group(140 cases)based on the BRCA results.Chi-square tests or independ-ent sample t-tests were used to compare the differences in clinicopathological characteristics and multiparametric MRI features between the BRCA mutation group and the wild group.Risk factors for BRCA-mutated BC were identified through univariate and multivariate logistic regression ananlyses,and a combined predictive model was constructed.Receiver operating characteristic(ROC)curve was used to ana-lyze the diagnostic efficacy of the model.Results There were statistically significant differences in T stage,human epidermal growth factor receptor 2(HER-2),Ki-67,non-mass enhancement,enhancement pattern,time-signal intensity curve(TIC)type,and apparent diffusion coefficient(ADC)values between the BRCA mutation group and the wild group.Univariate logistic regression analysis showed that T stage,HER-2,Ki-67,non-mass enhancement,enhancement pattern,TIC type,and ADC values were risk factors for BRCA-mutated BC(P<0.05).Multivariate logistic regression analysis revealed that T stage,HER-2,Ki-67,enhancement pattern,and TIC type were independent risk factors for BRCA-mutated BC(P<0.05).The combined model incorporating T stage,HER-2,Ki-67,enhancement pattern,and TIC type had the best diagnostic efficacy in predicting BRCA-mutated BC,with an area under the curve(AUC)of 0.751.Conclusion The combined model integrating T stage,HER-2,Ki-67,enhancement pattern,and TIC type has good efficacy in predicting BRCA-mutated BC.

Objective This study aims to explore the impact of changes in psychological status on non-suicidal self-inju-ry(NSSI)among junior high school students,in order to provide a theoretical basis for promoting their mental health development and to formulate more effective prevention and intervention measures.Methods A longitudinal study design was employed.Baseline data were collected in 2021(T1)from 652 first-year junior high school students selected through stratified cluster ran-dom sampling from two middle schools in a city.In 2023(T2),585 valid follow-up cases were obtained(effective response rate:89.72％).Chi-square tests,binary logistic regression,and ROC curve analysis were used to examine the effects of dynamic changes in psychological stress,internet addiction,depression,anxiety,and insomnia on NSSI(significance level α=0.05).Results ① Univariate analysis showed that the detection rate of NSSI significantly decreased from 22.05％(129/585)at T1 to 8.55％(50/585)at T2(x2=41.164,P＜0.001),with an average annual decline of 6.75％.Gender differences:the detec-tion rate decreased from 14.68％(43/293)to 5.80％(17/293)in boys(x2=18.577,P＜0.001),and from 29.45％(86/292)to 11.30％(33/292)in girls(x2=5.658,P=0.017),with a narrowing gender gap(T1:14.77％→ T2:5.70％).The NSSI detection rates between boys and girls were statistically significant at both time points(x2=18.577,5.658).② Com-parison between the persistent group and the NSSI-remission group showed that both decreased insomnia severity(OR=3.525,95％CI:1.230-10.105)and increased insomnia severity(OR=5.431,95％CI:1.895-15.570)were associated with an in-creased risk of NSSI persistence or onset(P＜0.01).③ Predictive efficacy:When scores of GAD-7+PHQ-9+ISI all in-creased by≥2 points,AUC=0.709,with a sensitivity of 44.0％-67.7％for predicting NSSI.When PHQ-9+ISI scores both increased by≥2 points,AUC=0.705,with a sensitivity of 50.2％-67.8％.Conclusion This study reveals a high natural re-mission rate of NSSI(82.17％,106/129 in the remission group)during junior high school,but also identifies gender heteroge-neity and persistent risks.Accumulated psychological stress,aggravated internet addiction,and worsened emotional disorders(anxiety/depression)are factors associated with NSSI persistence or onset.Clinical interventions should focus on monitoring dy-namic psychological indicators and early threshold identification.Although these results provide valuable insights,future research is needed to further explore the interaction mechanisms among these factors and how to effectively translate these findings into practical prevention and intervention measures.

Objective:To investigate and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.

Objective:To explore the preliminary clinical application efficacy of the side branch protection (SBP) technique in single stent-assisted coiling (SSAC) for the treatment of intracranial acute-angulated absolute wide neck bifurcation aneurysms (aWNBA).Methods:The clinical data of 23 patients with aWNBA treated at the Department of Interventional Medicine of the First Affiliated Hospital of Zhengzhou University from January 2013 to June 2024 were retrospectively collected. Patients were divided into two groups based on the stent type used: 11 in the side branch protection (SBP) group and 12 in the double stent-assisted coiling (DSAC) group. The characteristics of aWNBA including the size, the first and second angles between side branches and main artery, and the diameter of aneurysm, were analyzed preoperatively. Stent thromboembolism was recorded during the operation, and Raymond-Roy Occlusion Classification (RROC) and the modified Rankin Scale (mRS) were used to evaluate the treatment efficacy postoperatively. During the follow-up period the RROC and mRS were reevaluated and the stent stenosis was recorded. Mann-Whitney U test was used to compare the two groups′ data of skewed distribution, χ2 test and Fisher′s exact test were used to compare the two groups′ categorical data. Results:The 23 patients with aWNBA included 11 with aneurysms at the bifurcation of the middle cerebral artery, 6 at the top of the basilar artery, and 6 at the bifurcation of the anterior communicating artery. There was no statistically significant difference between the two groups in terms of aWNBA basic characteristics before operation (all P>0.05). The SBP group had a lower incidence of intraoperative stent thromboembolism and a lower mRS postoperatively compared to DSAC group (all P<0.05); meanwhile, there was no statistically significant difference between two groups on RROC after the operation ( P=0.949). During the follow-up period, the SBP group had lower rates of stent stenosis and mRS compared to the DSAC group (all P<0.05) and there was no statistically significant difference between two groups in RROC ( P=0.527). Conclusions:In cases of dense coiling on aWNBA, the SBP technique in SSAC is able to reduce incidence of the stent thromboembolism, stent stenosis as well as neurological injury; therefore, it is a safe and feasible therapeutic strategy for the aWNBA.

Coronary CT angiography(CCTA)plays an important role in study of coronary atherosclerotic plaques,which can be used to assess plaque composition and vulnerability,hence predicting major adverse cardiovascular events.Furthermore,CCTA combined with radiomics analysis is helpful for optimizing cardiovascular risk stratification.The research progresses in CCTA of coronary atherosclerotic plaques were reviewed in this article.

ObjectiveTo investigate the target proteins directly bound by neochlorogenic acid （NA） and the molecular mechanisms that ameliorate the proliferation and inflammatory response of psoriatic keratinocytes. MethodsM5-induced HaCaT cells were used as a psoriatic keratinocyte proliferation and inflammatory cell model. The synthesized NA probe （NA-P） and NA prodrug were first evaluated for cell viability using a cell proliferation/cell counting kit-8（CCK-8）. The potency of NA and NA-P was evaluated in the safe concentration range， and the effects of 0-100 μmol·L^-1 NA and probe on M5-induced proliferation of HaCaT cells were detected using CCK-8. The effects of 20， 40， 80 μmol·L^-1 NA and 80 μmol·L^-1 NA-P on the expression of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-23 （IL-23）， and interleukin-17A （IL-17A） inflammatory factors were detected by enzyme-linked immunosorbent assay （ELISA）， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the effects of NA on the mRNA expression of keratin 16 （K16） in HaCaT cells， S100 calcium-binding protein A9 （S100A9）， S100 calcium-binding protein A7 （S100A7）， IL-6， IL-17A， and chemokine 1 （CXCL1）. In vitro fluorescence labeling and competition experiments using NA-P were performed， and target protein angling and analysis using pull-down experiments combined with liquid chromatography-mass spectrometry （Pull-down/LC-MS/MS） were conducted. Target validation was performed using pull-down experiments combined with protein immunoblotting （Pull down-WB）， cellular heat transfer analysis combined with protein immunoblot （CETSA-WB） experiments， and molecular docking. Finally， Real-time PCR was utilized to detect the effects of 20， 40， 80 μmol·L^-1 NA and 80 μmol·L^-1 NA-P on the mRNA expression of IL-1β， nucleotide-binding oligomeric structural domain-like receptor protein 3 （NLRP3）， apoptosis-associated speckled-like protein （ASC）， and cysteine protease-1 （Caspase-1） in HaCaT cells. Protein immunoblot （Western blot） was used to detect the effects of phosphorylated p65 （p-p65）， p65， phosphorylated human nuclear factor-κB inhibitory protein α （p-IκBα）， human nuclear factor κB inhibitory protein α （IκBα）， and heat shock protein 90 （HSP90） expression. ResultsIn the 200 μmol·L^-1 safe concentration range， HaCaT cell proliferation， increased expression of TNF-α， IL-1β， IL-23， and IL-17A inflammatory factors， and increased mRNA expression of K16， S100A9， S100A7， IL-6， IL-17A， and CXCL1 were observed in the M5 group compared with the blank group. Cell proliferation in 5-100 μmol·L^-1 NA and NA-P groups was inhibited， and the expression of TNF-α， IL-1β， IL-23， and IL-17A inflammatory factors was decreased in the NA-L， NA-M， NA-H， and NA-P-H groups. The mRNA expression of K16， S100A9， S100A7， IL-6， IL-17A， and CXCL1 was decreased （P<0.05）. High-confidence targets were screened for HSP90 protein by Pull-down/LC-MS/MS using 200 μmol·L^-1 NA competing with 100 μmol·L^-1 NA-P. Compared with that in the blank group， the mRNA expression of NLRP3， IL-1β， ASC， and Caspase-1， as well as the expression of p-p65/p65， p-IκBα/IκBα， and HSP90 protein， were increased in HaCaT cells in the M5 group （P<0.05）. Compared with that in the M5 group， the mRNA expression of NLRP3， IL-1β， ASC， and Caspase-1 of cells in the NA-L group， the NA-M group， the NA-H group， and the NA-P-H group was decreased （P<0.05）. p-p65/p65 and p-IκBα/IκBα were decreased in the NA-M and NA-H groups （P<0.05）， and there was no change in HSP90 protein. Pull down-WB showed that NA could directly target HSP90 protein， and NA binding to HSP90 protein enhanced its thermal stability. Molecular docking of NA with HSP90 family proteins HSP90AA1， HSP90B1， and HSP90AB1 all resulted in highly stable binding. ConclusionNA can inhibit the proliferation and inflammatory response of psoriatic keratinocytes by a mechanism that may be achieved by targeting HSP90 to modulate the NF-κB/NLRP3 signaling pathway.