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 investigate the characteristics of oral and laryngeal diadochokinesis abilities and the developmental patterns of coordinated vocal fold movements in preschool children aged 3～6 years.Methods Sixty-one normal preschool children aged 3～6 years were selected to measure their maximum phonation time(MPT),as well as two types of acoustic parameters of oral and laryngeal diadochokinesis ability movements,including the as-sessment of one trisyllabic/pataka/diadochokinesis ability rate and four monosyllabic/?a/,/ha/,/?A/,/hA/la-ryngeal diadochokinesis ability rates.Results Diadochokinesis ability(DDK)and laryngeal diadochokinesis ability(LDDK)rates increased with age in preschool children aged 3～6 years,showing highly significant differences(P＜0.01).The growth rate of children's LDDK rates at age 4～5 years was the maximum within the 3～6 year age range.Children's MPT was highly significantly and positively correlated with DDK and LDDK(P＜0.01).The vo-cal fold adduction capacity in laryngeal diadochokinesis ability movements in children of all age groups was greater than vocal fold adduction ability/?a/LDDK＞/ha/LDDK(P＜0.01),/?A/LDDK＞/h∧/LDDK(P＜0.05).Con-clusion Age,MPT,and vocal fold adduction and abduction status had a significant effect on the oral and laryngeal diadochokinesis ability of preschool children aged 3～6 years old.The ages of 4～5 is a critical period for the devel-opment of children's oral and laryngeal diadochokinesis ability.

Objective This paper investigates the effect of a multi-physical field fusion intervention based on transcranial direct current stimulation(tDCS),transcranial magnetic stimulation(TMS)and music on mental fatigue.Methods After fatigue induction,10 subjects received blank group stimulation,music group stimulation and tDCS-TMS-Music stimulation,respectively.tDCS stimulation sites were located in the bilateral frontal regions of the subjects,and TMS stimulation sites were located in the bilateral occipital regions of the hindbrain.Heart rate variability and reaction performance were measured before and after each intervention to determine the elimination effect of different intervention programs on mental fatigue.Results Compared with the control group,the tDCS-TMS-Music group showed significantly greater improvements in subjective mental workload,response performance,and heart rate variability.Conclusion The results of this study support that tDCS-TMS-Music can effectively alleviate mental fatigue induced by long-term cognitive performance tasks,and the intervention effect is better than music intervention and resting-state relief at the same time.

Objective To explore the construction of a core competency framework and content for higher vocational speech-lan-guage-hearing rehabilitation technology programs based on World Health Organization rehabilitation competency framework(RCF). Methods Utilizing RCF and integrating the educational objectives for higher vocational speech-language-hearing reha-bilitation programs outlined by the Ministry of Education in 2022,as well as the technical documents from the In-ternational Association of Logopedics and Phoniatrics and the American Speech-Language-Hearing Association,this study analyzed the professional activities in speech-language-hearing rehabilitation technology to construct a competency framework based on RCF and give details in the specific content of each domain. Results The competency for speech-language-hearing rehabilitation technology encompassed seven domains:core val-ues,beliefs,practice,professionalism,learning and development,management and leadership,and research.Each domain was subdivided into specific competency elements and professional activities. Conclusion Establishing a higher vocational education system for speech-language-hearing rehabilitation technology based on RCF will help to set educational objectives,and construct curriculum systems,so that to cultivate practi-tioner who meet social needs and possess comprehensive professional skills and competencies.

Objective To study the characteristics of the working memory in patients with Chinese aphasia in different ways of tasks and test materials .Methods Fifteen aphasia patients (aphasia group ,54~70 years old) and fifteen matched normal cases (control group) were requested to finish auditory retelling and auditory recognition tests of numerical materials ,content and function words .The maximum length of the string correctly completed was referred to as the working memory span .The working memory span was compared between the two groups .Results The working memory span of the aphasia group was significantly smaller than that of in the normal group (P<0 .01) .The working memory span of in patients with the aphasia group in the positive sequence retelling tasks were significantly greater than in reverse retelling ,positive recognition and reverse recognition (P<0 .01) .Reverse retell-ing was significantly greater than reverse recognition (P<0 .01) .The positive recognition was significantly greater than the reverse recognition(P<0 .01) .In retelling tasks ,the order of the working memory span was numbers , function words ,content words from high to low in the aphasia group ,but there was no significant difference be-tween them .In the positive recognition tasks ,the average working memory span for the numerical material was sig-nificantly greater than the content words(P< 0 .01) and the function words(P< 0 .01) .The content words were greater than the function words(P<0 .01) .In the reverse recognition tasks ,average working memory span for the numerical material was significantly greater than the function words (P<0 .01) .Conclusion The working memoryspan of in patients with aphasics significantly lags behind the normal people .Numbers are the easiest for aphasics . In different task modes ,the difficulties from high to low are as follow :positive retelling ,reverse retelling ,positive recognition and reverse recognition .

Objective This study aimed to develop reading material for nasalance evaluation ,and find out na-salance scores associated with genders .Methods The NasalView ? (Tiger Electronics Inc .,Seattle ,USA) was used to obtain nasalance values in the new and old material .A total of 102 subjects (51 males ,51 females) who have lived in Beijing for 18 years or longer at the time of the experiment received the tests ,the results from two pieces of material and the mean nasalance gender score differences were compared .Results The mean nasalance scores of sen-tences were 56 .58% ± 3 .43% for'Nasal sentence',33 .86% ± 5 .24% for'Oral sentence',and 49 .49% ± 4 .13% for'Oro -nasal sentence'respectively in the new material .The mean nasalance scores of sentences were 54 .31% ± 4 .43% for'Nasal sentence',35 .64% ± 5 .90% for'Oral sentence',and 47 .12% ± 4 .96% for'Oro-nasal sentence're-spectively in the old material .There were significant differences between males and females through materials .The nasalance gender score differences showed that females were bigger than males (P<0 .01) .This study found a cor-relation between the new and old materials :'Nasal sentence'(r=0 .899 ,P< 0 .01) ,'Oral sentence'(r= 0 .850 ,P<0 .01) ,and'Oro -nasal sentence'(r=0 .851 ,P<0 .01) .The standard error difference showed that the new was smaller than the old (P<0 .01) .Conclusion The new material for nasalance evaluation has a better test validity ,and there is a high correlation between the old materials .The usage of the new material for nasalance evaluation will produce more accurate results with higher credibility .Normal female's nasalance scores were higher than males .

Objective To comparative analysis the rabbit VX2 tumors angiogenesis in fatty liver and normal liver,and investigate the correlation of contrast-enhanced ultrasound (CEUS) parameters and their angiogenesis.Methods Rabbit models of fatty liver and normal liver with implanted VX2 tumors were established.Two groups of hepatic backgrounds and VX2 tumors were analyzed by QontraXt quantitative software of CEUS.The expression level of tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) were detected with immunohistochemical techniques and real-time fluorescence quantitative PCR (FQ-PCR).Results ①No significant difference was found in MVD,VEGF protein and gene expression between VX2 tumors in normal liver and fatty liver.The expression of VEGF gene in fatty liver parenchyma were lower than normal liver parenchyma (P ＜0.05).②There was positive correlation between MVD and peak intensity (r =0.494,P ＜0.05; r =0.591,P ＜0.01) both in fatty liver and normal liver VX2 tumors.The expression of VEGF protein were not correlated with TIC parameters (all P ＞ 0.05).③The MVD had positive correlation with expression of VEGF protein in fatty liver and normal liver VX2 tumors (r =0.508,P ＜0.05; r =0.570,P ＜0.01).Conclusions The expression of MVD and VEGF had no significant difference between fatty liver and normal liver VX2 tumors.The peak intensity of VX2 tumors CEUS had positive correlation with MVD both in fatty liver and normal liver,which can indirectly reflect MVD expression level and help to evaluate tumor angiogenesis.

Objective To investigate the conventional ultrasound characteristics of VX2 tumors in fatty liver and normal liver of rabbits,furthermore,to analysis the blood flow characteristics of them with contrast-enhanced ultrasound (CEUS).Methods Rabbit model of fatty liver and normal liver with implanted VX2 tumors were established,and examined using conventional and CEUS.QontraXt quantitative software of CEUS was used.Results The fatty liver models with 20 VX2 tumors and normal liver models with 23 VX2 tumors were successfully developed in rabbits.In conventional ultrasonography,hyperechoic VX2 tumor lesions in fatty liver were far less than them in normal liver (P =0.008).No significant difference was found in iso-echoic and hypoechoic VX2 tumor lesions between two groups (P ＞ 0.05).Compared with normal liver parenchyma,arrival time of fatty liver parenchyma was later,peak intensity was lower (P ＜0.05).There was no significant difference in arrival time,peak intensity,sharpness,area under curve between the VX2 tumors of normal liver and fatty liver (P ＞ 0.05).Conclusions There is a significant difference characteristic in conventional ultrasonography between VX2 tumors in fatty liver and normal liver.Fatty liver blood perfusion effects are lower than normal liver in CEUS.Quantitative parameters of CEUS are more objective and accurate for hemodynamic of VX2 tumors and fatty liver.

Objective To analyze hepatic inflammatory pseudoneoplasm with fatty liver and normal liver perfusion blood characteristics and quantitative parameters using real-time contrast-enhanced ultrasound (CEUS) and time intensity curve.Methods Twenty rabbits (including ten with fatty liver and ten with normal liver) with thirty-nine inflammatory pseudoneoplasm of the liver (IPL) were studied by low mechanical index CEUS with bolus injection of SonoVue via peripheral auricular vein and QontraXt quantitative analysis software.IPL contrast-enhanced ultrasound blood perfusion characteristics with two different liver background were analyzed.Results ①According to the different pathological elements,IPL showed four kinds of CEUS types:one lesion showed absent contrast enhancement pattern (type Ⅰ),nineteen lesions showed iso-enhancement pattern (type Ⅱ),six lesions showed hypo-enhancement pattern (type Ⅲ),thirteen lesions showed fast-in and fast-out pattern (type Ⅳ).②Compared with normal liver,arrival time of fatty liver was later and its peak intensity was lower.②Compared with peripheral parenchyma,arrival time of IPL was later,peak intensity was lower and its sharpness was sharper (P ＜0.05).④Between IPL lesions with two different liver background,there was no significant difference about parameters of the time-intensity curve (P ＞0.05).Conclusions Due to different pathological elements,IPL lesions have multiform perfusion patterns in CEUS.CEUS and time intensity curve could provide enough perfusion information for IPL and liver parenchyma more accurately.

Objective Through constructing prokaryotic expression vector pET-30a-GPI-B7-1, to gain purified GPI-B7-1 fusion protein so as to confirm the tumor immune effect. Methods The DNA fragment encoding the signal for GPI-anchor attachment of hPLAP-1 and the cDNA encoding the human costimulatory molecule CD80 ( BT-1 ) were cloned from fresh placenta and human peripheral blood monocytes (PBMC) respectively. The two fragment were annealed to form a fusion gene (GPI-BT-1) by PCR. Then the fusion gene was inserted into the prokaryotic expression vector pET-30a, resulting in pET-30a-GPI-BT-1. Transfer to E. coli BL21, purified fusion protein were analysed by SDS-PAGE and Western blot. Results Agarose gel electrophoresis map of GPI and BT-1 PCR products show that GPI goal gene strap was seen at 133bp region and BT-1 goal gene strap at 792 region. Identification of recombinant pET-30a-GPI-B7-1 by restriction enzyme and PCR illustrate two goal fragment for 5000 bp and 900 bp, to realize the expression of fusion gene ( GPI-B7-1 ) at the E. coli BL21. The fusion protein was successfully produced in the pET expression system induced by IPTG and purified by Ni2 + -NTA agarose column. By SDS-PAGE and Western blot analysis, the observed molecular weight of the fusion protein was 38 kDa. Conclusion The purified GPI-B7-1 fusion protein can be obtained from E. coli BL21 transfered by prokaryotic expression vector pET-30a-GPI-B7-1, which will prove useful tool for the study of tumor immune therapy.