Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

ObjectiveTo analyze the epidemiological features and influencing factors of rabies in Shanxi Province，and to provide evidence to further promote the elimination of rabies in Shanxi Province. MethodsThe incidence data of rabies in Shanxi from 2011 to 2022 were collected and subjected to descriptive analysis. ResultsFrom 2011 to 2022， a total of 348 rabies cases were reported in Shanxi Province， with an average annual incidence of 0.080 3/10⁵. The incidence of rabies showed a downward trend overall. The highest incidence was in August. The cases were mainly farmers， mostly males， and most cases were reported between 50 and 69 years old. The data of cases showed that dogs were the main animals attacking human （93.96%）. The incubation period of most cases was 1‒3 months （37.37%）.The main exposure site was hand（51.33%）. Only 2.66% cases with grade Ⅲ exposure were injected with passive immune agents. ConclusionThe incidence of rabies in Shanxi Province continues to decrease， but there are still loopholes in prevention and control measures. It is necessary to strengthen the management and immunization of dogs，health education， and standardized procedures after exposure to maintain the achievements in the prevention and control of rabies.

Objective To construct,implement and evaluate the effectiveness of the virtual simulation technology-based prenatal health education course.Methods The curriculum included 4 parts:"warm delivery room and easy delivery","medicated analgesic delivery","non-medicated analgesic delivery"and"early maternal and infant health care".From May to September 2022,100 primiparas in an obstetrics and gynecology hospital in Zhejiang Province were investigated by convenient sampling method.Random number table method was used to divide the participants into an experimental group and a control group,with 50 participants per group.The control group received conventional health education,while the experimental group received an augmented virtual reality technology-based prenatal health education course during the late stages of pregnancy on this basis.We conducted a post-intervention comparative analysis of antenatal anxiety levels,fear of childbirth,and birth outcomes between the 2 groups.Furthermore,a post-intervention satisfaction survey was administered to the experimental group.Results After intervention,the antenatal anxiety of the experimental group was lower than that of the control group(x2=4.943,P=0.026),and the decrease in fear of childbirth scores was higher than that of the control group(t=3.200,P=0.002).The experimental group was highly satisfied with all of the 4 dimensions of the course,and the overall evaluation was(31.8±3.23)points.However,there were no significant differences in vaginal delivery rate,postpartum bleeding volume,postpartum hemorrhage incidence,perineal injury degree and duration of each labor stage between the 2 groups(P＞0.05).Conclusion The virtual reality technology-based prenatal health education course was effective in improving the antenatal anxiety and fear of childbirth of primipara,and the use satisfaction is high.

To address the issue that the existing weakly supervised segmentation methods have difficulties in obtaining fine-grained glandular features from colorectal pathological images,leading to the inability to generate high-quality pseudo-labels and compromising the gland segmentation performance,a dual-branch network based on weakly supervised learning is proposed for gland segmentation in colorectal pathological image.The patch-level colorectal pathological images are input into the first branch network,where the interaction and fusion of local and global features of patch-level images are achieved through the feature interaction module and affinity attention fusion module,and fine-grained glandular features are obtained.Subsequently,image-level colorectal pathological images are input into the second branch network,where the gland locations are located using the partial class activation attention module,and coarse-grained class activation maps are obtained.Finally,high-quality pseudo-labels are derived from the fine-grained glandular features and coarse-grained class activation maps,and gland segmentation is realized in the segmentation network through the cross-scale connected spatial perception module.The tests on two colorectal pathological image datasets(GlaS and CRAG)reveal that the proposed method is superior to other segmentation methods in segmentation performance,confirming its effectiveness.

High-precision segmentation of melanoma images is crucial for early diagnosis and improving patient survival.However,the blurring of the edge region of melanoma,which presents irregular shapes,makes it difficult for existing segmentation methods to obtain edge feature information,affecting the accuracy of melanoma image segmentation.To solve this problem,a melanoma image segmentation method based on edge key points and edge attention is proposed.An edge key point selection module for point rendering and a combined convolution transformer block are designed in the encoder to guide the acquisition of local and global features of the edge by selecting edge key points.Then,the edge refinement module is designed in the encoder to refine the edge features of the deep network,and finally,the multi-scale edge attention module is designed in the skip connection,which enables the capture of the edge shape features at multiple scales.The tests on two datasets(ISIC 2018 and PH2)demonstrate that the proposed method has better segmentation performance than the existing segmentation methods.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective Based on the bio-psycho-social model of functioning and health of International Classification of Function-ing,Disability and Health(ICF)framework,this paper systematically analyzes rehabilitation-related policy docu-ments of the World Health Organization(WHO)to explore the theoretical and policy principles,service systems,priority development areas,and main policy and technical measures for speech and language rehabilitation for children with hearing impairment. Methods Under literature research and policy analysis methods,this paper systematically reviewed the functioning and health framework of ICF,relevant WHO policy reports and American Speech and Hearing Association technical documents,analyzed the current status and needs of rehabilitation services in China,and proposed a theoretical framework,priority areas,and main policy and technical measures for constructing an ICF-based speech and lan-guage rehabilitation service system for children with hearing impairment. Results There were eight major principles for the development of speech and language rehabilitation for children with hearing impairment:child-centered and respect for individual differences,life-cycle support and promoting con-tinuous development,evidence-based practice,multidisciplinary collaboration,building family participation sup-port networks,promoting integrated education and social participation,focusing on cultural sensitivity,and tech-nology-empowered rehabilitation innovation.Five service systems were elaborated,including comprehensive ear-ly screening,diagnosis,and intervention system;family and social support system;multidisciplinary team servic-es system;comprehensive,multi-level speech and language rehabilitation service system;and digitally empow-ered services to build new rehabilitation service models.The priority development areas,and main policy and technical measures for speech and language rehabilitation for children with hearing impairment were also dis-cussed. Conclusion Based on the bio-psycho-social model of functioning and health of ICF,comprehensive,personalized,con-tinuous,high-quality and universally accessible speech and language rehabilitation services can be developed by implementing measures,such as strengthening policy support,improving service systems,cultivating multidisci-plinary professionals,promoting digital empowerment technologies and enhancing support system,to promote the overall development,social participation and quality of life for children with hearing impairment.

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 construct a curriculum system for higher vocational education in speech-language-hearing rehabilitation based on the World Health Organization rehabilitation competency framework(RCF),to align with international standards. Methods Based on RCF,curriculum theory and principles of vocational education psychology,a curriculum system and its content for higher vocational education in speech-language-hearing rehabilitation were developed.The curric-ulum content and core competencies were analyzed in detail across four levels:basic courses,specialized basic courses,specialized core courses and practical training courses. Results From the perspective of the seven competency domains of RCF,the theoretical and practical significance of con-structing a speech-language-hearing higher vocational education curriculum system based on RCF was systemati-cally elaborated.The study emphasized the importance of establishing competency-oriented higher vocational re-habilitation education for developing students'professional competence,adapting to job requirements,and pro-moting career development.A curriculum content system for speech-language-hearing rehabilitation higher voca-tional education based on RCF was systematically constructed,encompassing basic courses,professional cours-es,and practical training courses.The course names,main content and competency objectives at each level were analyzed in detail. Conclusion It is important to develop the course system of higher vocational education of speech-language-hearing reha-bilitation based on RCF.By comparing with international standards,the curriculum is optimized,focusing on im-proving students'vocational competence and promoting the international development.The curriculum system covers key areas such as core values,beliefs,practice and professionalism,integrates basic,core and practical training courses to achieve a competence-oriented curriculum system for higher vocational speech-language-hear-ing rehabilitation education.

Objective:To analyze the histopathological characteristics of peri-implant soft tissue in re-constructed jaws and the changes after keratinized mucosa augmentation(KM A)with free gingival graft(FGG).Methods:Twenty patients were enrolled in this study.Five patients of them,who were perio-dontal and systemic healthy and referred for crown lengthening before restoration with healthy keratinized gingiva collected were enrolled as healthy controls.15 patients of them were with fibula or iliac bone flaps jaw reconstruction(10 with fibula flap and 5 with iliac flap),who were referred to FGG and implant exposures before restoration.Soft tissue was collected before FGG in reconstructed jaws,and in 5 patients(3 with fibula flap and 2 with iliac flap)8 weeks after FGG if a second surgery was conducted.Histologi-cal analysis with hematoxylin-eosin stain and immunological analysis to interlukin-1(IL-1),interlukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were performed.Results:Thickness from the bottom of stratum basale to the top of stratum granulosum and thickness of keratinized layer in reconstructed jaws were significantly lower compared with that of natural healthy keratinized gingiva[0.27(0.20,0.30)mmvs.0.36(0.35,0.47)mm,P＜0.05;16.49(14.90,23.37)μm vs.26.37(24.12,31.53)μm,P＜0.05].In the reconstructed area,thickness from the bottom of stratum basale to the top of stra-tum granulosum increased after KMA with FGG[0.19(0.16,0.25)mm vs.0.38(0.25,0.39)mm,P=0.059]and the thickness of keratinized layer significantly increased after KMA with FGG[16.42(14.16,22.35)μm vs.28.57(27.16,29.14)μm,P＜0.05],which was similar to that in the con-trol group.Furthermore,the number of positive cells of IL-1,IL-6 and TNF-α significantly increased after KMA[0.67(0.17,8.93)vs.11.00(9.16,18.00);13.00(8.50,14.14)vs.21.89(15.00,28.12);0.22(0.04,0.63)vs.2.83(1.68,5.00),respectively,P＜0.05]as well as the average optical density value[0.15(0.14,0.17)vs.0.18(0.17,0.21);0.28(0.26,0.33)vs.0.36(0.33,0.37);0.23(0.22,0.29)vs.0.30(0.28,0.42),respectively,P＜0.05],which was similar to that in the healthy keratinized gingiva.Conclusion:The lack of rete pegs and inflammato-ry factors were common in soft tissue with jaw reconstruction.FGG can improve the quality of the epithe-lium and may improve the stability of the mucosa around implants.