Objective:To explore the value of ultrasound elastography (USE) in evaluating the stability and prognosis of carotid plaque (CP) in patients with cerebral infarction(CI).Methods:A total of 94 patients with CI admitted to Dongying District People′s Hospital of Dongying City from January 2022 to December 2023 were retrospectively selected as the study objects, all of whom were treated with carotid artery dissection. The presence of CP was confirmed by pathological examination. The head and neck of patients were examined by conventional ultrasound and USE before surgery, respectively, and the diagnostic value of the two methods on CP stability was compared. The difference of strain value and strain rate among different plaque types was compared, and the correlation between different plaque types and the score of ESSEN Stroke Risk Scale (ESRS) was analyzed.Results:The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of conventional ultrasonic detection of CP were 75.00%, 71.43%, 74.00%, 87.10% and 52.63%; and of USE were 90.28%, 89.29%, 90.00%, 95.59%, 78.13%. The strain values and strain rates of stable plaques were lower than those of vulnerable plaques : (0.73 ± 0.11) × 10 3 vs. (2.42 ± 0.57) × 10 3, (6.57 ± 0.84) s -1 vs. (9.36 ± 2.55) s -1, there were statistical differences ( P<0.01). The ESRS scores of patients with vulnerable plaques were mostly ≥3 scores, and those with stable plaques were mostly<3 scores, there was statistical differences ( P<0.01). The scores of National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) 3 months after the onset of stable plaque were lower than those of vulnerable plaque patients: (26.80 ± 8.47) scores vs. (34.67 ± 8.98) scores, (3.97 ± 0.84) scores vs. (4.55 ± 1.61) scores, there were statistical differences ( P<0.01 or <0.05). Conclusions:USE has significant advantages in detecting CP stability in CI patients, which can efficiently and accurately assess the risk of plaque and provide important information for clinical use.

Objective:To investigate the phenomenon of hippocampal ferroptosis and its change in a rat model of chronic constriction injury(CCI)of the sciatic nerve,as well as the association between hippocampal ferroptosis and emotional disorders induced by neuro-pathic pain.Methods:A total of 32 male Sprague-Dawley rats were randomly divided into Sham group,CCI group,CCI+F group,and CCI+E group,with 8 rats in each group.The rats in the CCI+F group and the CCI+E group were given intraperitoneal injection of Ferrostatin-1(10 mg/kg)and Erastin(10 mg/kg),respectively,since day 7 after surgery for two consecutive days.Mechanical with-drawal threshold(MWT),paw withdrawal latency(PWL),and open field test(OFT)were measured before surgery and on days 7 and 14 after surgery.On day 14 after surgery,the rats were sacrificed to col-lect hippocampal tissue;Western blot was used to measure the levels of GPX4,xCT,and FTH1;related kits were used to measure the expression levels of MDA and GSH;HE staining,Nissl staining,and immunofluorescent staining were performed;transmission electron microscopy was used to observe the structural changes of the mito-chondria.Results:In terms of behavioristics,compared with the Sham group,the CCI group had significant reductions in MWT and PWL on day 7 after surgery(P<0.001),with further reductions from day 7 to day 14 after surgery(P<0.001);compared with the CCI group,the CCI+F group had significant increases in MWT and PWL on day 14 after surgery(P<0.001),and the CCI+E group had no significant change in MWT and a significant reduction in PWL(P<0.01).In terms of the OFT test,compared with the Sham group,the CCI group had significant reductions in total distance and number of central squares crossed(P<0.001)and a significant increase in immobility time(P<0.001);compared with the CCI group,the CCI+F group had significant increases in total distance and number of central squares crossed and a significant reduction in immobility time,while the CCI+E group had no significant changes in these indi-ces.In terms of biochemical results,compared with the Sham group,the CCI group had significant reductions in GPX4,xCT,and FTH1(P<0.01),a significant increase in MDA,and a significant reduction in GSH;compared with the CCI group,the CCI+F group had sig-nificant increases in GPX4,xCT,and FTH1(P<0.05),a significant reduction in MDA(P<0.001),and a significant increase in GSH(P<0.01),and the CCI+E group had significant reductions in xCT and FTH1,with no significant changes in MDA and GSH.In terms of morphology,compared with the Sham group,the CCI group had damage and necrosis of hippocampal neurons,significant reductions in Nissl bodies and c-Fos level(P<0.05),and significantly damaged mitochondrial cristae on day 14 after surgery;compared with the CCI group,the CCI+F group had intact structures of hippocampal neurons,significant increases in Nissl bodies and c-Fos(P<0.05),and relatively intact mitochondria,while there were no significant differences in c-Fos and Nissl bodies between the CCI+E group and the CCI group.The pairwise linear correlation analysis of PWL,MWT,GPX4,OFT,and c-Fos on day 14 after surgery showed a signifi-cantly positive correlation between any two indicators(P<0.01).Conclusion:Peripheral nerve injury triggers ferroptosis in the hippo-campus and causes anxiety and depression,thereby aggravating ferroptosis and accelerating the development of central hyperalgesia.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective:To explore the intervention effects of the skill training for parents with autism child (STPAC) on toddlers with autism spectrum disorder (ASD).Methods:A multicenter non-randomized concurrent controlled study design was conducted. Thirty children with ASD aged 15-30 months, first diagnosed at the Children′s Hospital of Fudan University, the First Hospital of Jilin University, and Chengdu Women′s and Children′s Central Hospital from 2019 to 2020, were enrolled in the STPAC group. Thirty children with ASD who visited the same hospitals during the same period but refused the STPAC intervention were selected as the control group. The STPAC group received an 8-week intervention (3 h/week) followed by quarterly follow-ups for 1 year, while the control group voluntarily chose community-based routine interventions. The Griffiths development scales-Chinese (GDS-C) was used to assess the developmental levels, and the communication and symbolic behavior scales developmental profile infant-toddler checklist (CSBS-DP-ITC) was completed by the primary caregivers to evaluate social, language and symbolic behavior. The independent samples t-tests or Mann-Whitney U tests, etc.was used for inter-group comparison. The paired t-tests or Wilcoxon signed-rank tests, etc. was used for inter-group pre-post intervention comparison. Results:The STPAC group included 30 children (22 males and 8 females, aged (23.9±2.2) months), and the control group included 30 children (20 males and 10 females, aged (24.2±2.6) months). Before the intervention, there were no statistically differences in GDS-C development quotient (DQ) and CSBS-DP-ITC scores between groups (all P>0.05). After 1-year intervention, GDS-C DQ in personal-social, hearing-language, hand-eye coordination, performance domains of STPAC group and GDS-C DQ in personal-social, hearing-language domains of control group were all increased (all P<0.01). After 1-year intervention, CSBS-DP-ITC scores of both groups were all improved in socia, language, symbolic behavior, and total scores (all P<0.001). GDS-C DQ changes before and after 1 year of intervention in hearing-language, hand-eye coordination, performance domains of the STPAC group were all higher the those of control group (34(15, 48 vs. 10(-4, 39), 11±20 vs. -1±19, 23±25 vs. 8±22, all P<0.05). CSBS-DP-ITC scores changes before and after 1 year of intervention in social and total scores of the STPAC group were both higher the those of control group (10(5, 30) vs. 3(1, 7), 26±17 vs. 11±8, both P<0.001). Conclusion:Compared with the community routine interventions, the STPAC better improves the language, hand-eye coordination, visual-spatial, social communication, and play skills in ASD toddlers.

Objective:To explore the value of ultrasound elastography (USE) in evaluating the stability and prognosis of carotid plaque (CP) in patients with cerebral infarction(CI).Methods:A total of 94 patients with CI admitted to Dongying District People′s Hospital of Dongying City from January 2022 to December 2023 were retrospectively selected as the study objects, all of whom were treated with carotid artery dissection. The presence of CP was confirmed by pathological examination. The head and neck of patients were examined by conventional ultrasound and USE before surgery, respectively, and the diagnostic value of the two methods on CP stability was compared. The difference of strain value and strain rate among different plaque types was compared, and the correlation between different plaque types and the score of ESSEN Stroke Risk Scale (ESRS) was analyzed.Results:The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of conventional ultrasonic detection of CP were 75.00%, 71.43%, 74.00%, 87.10% and 52.63%; and of USE were 90.28%, 89.29%, 90.00%, 95.59%, 78.13%. The strain values and strain rates of stable plaques were lower than those of vulnerable plaques : (0.73 ± 0.11) × 10 3 vs. (2.42 ± 0.57) × 10 3, (6.57 ± 0.84) s -1 vs. (9.36 ± 2.55) s -1, there were statistical differences ( P<0.01). The ESRS scores of patients with vulnerable plaques were mostly ≥3 scores, and those with stable plaques were mostly<3 scores, there was statistical differences ( P<0.01). The scores of National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) 3 months after the onset of stable plaque were lower than those of vulnerable plaque patients: (26.80 ± 8.47) scores vs. (34.67 ± 8.98) scores, (3.97 ± 0.84) scores vs. (4.55 ± 1.61) scores, there were statistical differences ( P<0.01 or <0.05). Conclusions:USE has significant advantages in detecting CP stability in CI patients, which can efficiently and accurately assess the risk of plaque and provide important information for clinical use.

Objective:To explore the intervention effects of the skill training for parents with autism child (STPAC) on toddlers with autism spectrum disorder (ASD).Methods:A multicenter non-randomized concurrent controlled study design was conducted. Thirty children with ASD aged 15-30 months, first diagnosed at the Children′s Hospital of Fudan University, the First Hospital of Jilin University, and Chengdu Women′s and Children′s Central Hospital from 2019 to 2020, were enrolled in the STPAC group. Thirty children with ASD who visited the same hospitals during the same period but refused the STPAC intervention were selected as the control group. The STPAC group received an 8-week intervention (3 h/week) followed by quarterly follow-ups for 1 year, while the control group voluntarily chose community-based routine interventions. The Griffiths development scales-Chinese (GDS-C) was used to assess the developmental levels, and the communication and symbolic behavior scales developmental profile infant-toddler checklist (CSBS-DP-ITC) was completed by the primary caregivers to evaluate social, language and symbolic behavior. The independent samples t-tests or Mann-Whitney U tests, etc.was used for inter-group comparison. The paired t-tests or Wilcoxon signed-rank tests, etc. was used for inter-group pre-post intervention comparison. Results:The STPAC group included 30 children (22 males and 8 females, aged (23.9±2.2) months), and the control group included 30 children (20 males and 10 females, aged (24.2±2.6) months). Before the intervention, there were no statistically differences in GDS-C development quotient (DQ) and CSBS-DP-ITC scores between groups (all P>0.05). After 1-year intervention, GDS-C DQ in personal-social, hearing-language, hand-eye coordination, performance domains of STPAC group and GDS-C DQ in personal-social, hearing-language domains of control group were all increased (all P<0.01). After 1-year intervention, CSBS-DP-ITC scores of both groups were all improved in socia, language, symbolic behavior, and total scores (all P<0.001). GDS-C DQ changes before and after 1 year of intervention in hearing-language, hand-eye coordination, performance domains of the STPAC group were all higher the those of control group (34(15, 48 vs. 10(-4, 39), 11±20 vs. -1±19, 23±25 vs. 8±22, all P<0.05). CSBS-DP-ITC scores changes before and after 1 year of intervention in social and total scores of the STPAC group were both higher the those of control group (10(5, 30) vs. 3(1, 7), 26±17 vs. 11±8, both P<0.001). Conclusion:Compared with the community routine interventions, the STPAC better improves the language, hand-eye coordination, visual-spatial, social communication, and play skills in ASD toddlers.

Objective To evaluate the analgesic effects of ultrasound-guided hip capsule block and fascia iliaca block in elderly patients undergoing hip replacement surgery and their impacts on postoperative rehabilitation.Methods A total of 44 patients who underwent total hip replacement in the Second Affiliated Hospital of Wenzhou Medical University from May to December in 2023 were selected and divided into fascia iliaca block group(group F)and hip capsule block group(group H)according to the random number table,with 22 cases in each group.All patients were anesthetized by lumbar anesthesia combined with nerve block.The primary indicators included the recovery of lower limb muscle strength at 8h,24h,48h after operation and the rest and movement visual analogue scale(VAS)scores at each observation point.The secondary indicators were sufentanil consumption of analgesic pump,the number of compressions,the use rates of additional parecoxib sodium in ward,the length of hospital stay and the occurrence of adverse reactions.Results The recovery of lower limb muscle strength in group H was better than that in group F at 8h and 24h after operation,and the difference was statistically significant(P<0.05).The rest and movement VAS scores at 30min after block and 4h after operation in group H were significantly lower than those in group F(P<0.05),while there were no significant differences in the rest and movement VAS scores between two groups at other time points(P>0.05).The rest and movement VAS scores at each time point after blockade were lower than those before blockade in two groups(P<0.05).The sufentanil consumption in analgesic pump and the number of compressions in group H was lower than that in group F at 4h after operation(P<0.05),and there were no significant differences in analgesic pump data and the use rates of parecoxib sodium between two groups at subsequent time points(P>0.05).There were no statistically significant difference in the incidence of nausea within 48h after operation and hospital stay between two groups(P>0.05).Conclusion Both fascia iliaca block and hip capsule block can be safely and effectively used in elderly patients with hip replacement,but the analgesic effect of hip capsule block is faster,the early postoperative analgesic effect is better,and the impact on lower limb movement is less.

Objective To evaluate the analgesic effects of ultrasound-guided hip capsule block and fascia iliaca block in elderly patients undergoing hip replacement surgery and their impacts on postoperative rehabilitation.Methods A total of 44 patients who underwent total hip replacement in the Second Affiliated Hospital of Wenzhou Medical University from May to December in 2023 were selected and divided into fascia iliaca block group(group F)and hip capsule block group(group H)according to the random number table,with 22 cases in each group.All patients were anesthetized by lumbar anesthesia combined with nerve block.The primary indicators included the recovery of lower limb muscle strength at 8h,24h,48h after operation and the rest and movement visual analogue scale(VAS)scores at each observation point.The secondary indicators were sufentanil consumption of analgesic pump,the number of compressions,the use rates of additional parecoxib sodium in ward,the length of hospital stay and the occurrence of adverse reactions.Results The recovery of lower limb muscle strength in group H was better than that in group F at 8h and 24h after operation,and the difference was statistically significant(P<0.05).The rest and movement VAS scores at 30min after block and 4h after operation in group H were significantly lower than those in group F(P<0.05),while there were no significant differences in the rest and movement VAS scores between two groups at other time points(P>0.05).The rest and movement VAS scores at each time point after blockade were lower than those before blockade in two groups(P<0.05).The sufentanil consumption in analgesic pump and the number of compressions in group H was lower than that in group F at 4h after operation(P<0.05),and there were no significant differences in analgesic pump data and the use rates of parecoxib sodium between two groups at subsequent time points(P>0.05).There were no statistically significant difference in the incidence of nausea within 48h after operation and hospital stay between two groups(P>0.05).Conclusion Both fascia iliaca block and hip capsule block can be safely and effectively used in elderly patients with hip replacement,but the analgesic effect of hip capsule block is faster,the early postoperative analgesic effect is better,and the impact on lower limb movement is less.

OBJECTIVE To explore the mechanism of action of epigallocatechin-3-gallate(EGCG) in inhibiting laryngeal cancer cells. METHODS The expression of epidermal growth factor receptor(EGFR) in laryngeal cancer cell lines AMC-HN-8, TU686 and TU212 was detected by Western blotting, and the inhibitory effects of cetuximab and EGCG on three laryngeal cancer cells were detected by CCK-8 assay. A lentiviral vector containing EGFR promoter and Luc reporter gene was constructed to generate a TU686-EGFR-Luc cell line that could steadily express Luc activity. Luciferase assay was performed to evaluate the effect of EGCG on the transcription activity of EGFR promoter. Cell cycle and apoptosis of EGCG-treated laryngeal carcinoma cells were analyzed by flow cytometry, and changes of the levels of EGFR and downstream ERK1/2, cell cycle-associated proteins P53 and P27, apoptosis-associated proteins BCL2 and PART, and autophagy marker LC3A/B were further examined. RESULTS The laryngeal carcinoma cell lines were insensitive to cetuximab but could be effectively suppressed by EGCG. EGCG effectively inhibited the transcription activity of EGFR promoter. Treatment of TU686 cells at sub-IC50 dose EGCG resulted in significant cell cycle arrest at S phase with partial apoptosis. Significant inhibition of expression and activation of EGFR and downstream signaling pathway were observed. CONCLUSION EGCG can effectively downregulate EGFR and suppress laryngeal carcinoma cells, further investigation on in vivo effect and mechanisms are anticipated.

ERα-36 is a novel subtype of estrogen receptor α which promotes tumor cell proliferation, invasion and drug resistance, and it serves as a therapeutic target. However, only small-molecule compounds targeting ERα-36 are under development as anticancer drugs at present. Gene therapy approach targeting ERα-36 can be explored using recombinant adenovirus armed with decoy receptor. The recombinant shuttle plasmid pDC316-Ig κ-ERα-36-Fc-GFP was constructed via genetic engineering to express an Ig κ-signaling peptide-leading secretory recombinant fusion protein ERα-36-Fc. The recombinant adenovirus Ad-ERα-36-Fc-GFP was subsequently packaged, characterized and amplified using AdMax^TM adenovirus packaging system. The expression of fusion protein and functional outcome of Ad-ERα-36-Fc-GFP transduction were further analyzed with triple-negative breast cancer MDA-MB-231 cells. Results showed that the recombinant adenovirus Ad-ERα-36-Fc-GFP was successfully generated. The virus effectively infected MDA-MB-231 cells which resulted in expression and secretion of the recombinant fusion protein ERα-36-Fc, leading to significant inhibition of EGFR/ERK signaling pathway. Preparation of the recombinant adenovirus Ad-ERα-36-Fc-GFP provides a basis for further investigation on cancer gene therapy targeting ERα-36.
Adenoviridae/genetics* ; Cell Proliferation ; Estrogen Receptor alpha/metabolism* ; Recombinant Proteins ; Transfection