OBJECTIVE: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. METHODS: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. RESULTS: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. CONCLUSION Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Adult ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Patellofemoral Joint/surgery* ; Recurrence ; Plastic Surgery Procedures/methods* ; Patella/surgery* ; Treatment Outcome

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

OBJECTIVES: To investigate the role of METTL3 and FOXO3 in anthracycline resistance in acute myeloid leukemia (AML) cells. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were performed in anthracycline-resistant and sensitive HL60 and K562 cells with lentivirus-mediated knockdown or overexpression of METTL3 and FOXO3. TCGA and GSE6891 datasets were used for analysis of the clinical and gene expression data of AMI patients. FOXO3 expressions at the mRNA and protein levels in the transfected cells were detected with RT-qPCR and Western blotting, and the changes in cell proliferation and apoptosis were evaluated using CCK8 assay and flow cytometry; the expression of m⁶A-modified mRNA and mRNA stability of FOXO3 was detected analyzed using MeRIP-qPCR and RT-qPCR. Functional enrichment analysis of the differential genes in the transfected cells was performed. RESULTS: Differential gene analysis in anthracycline-resistant versus sensitive AML cells and in cells with METTL3 knockdown revealed the enrichment in FoxO and autophagy pathways (P<0.05), and the anthracycline-resistant cells showed significantly increased m⁶A modification of FOXO3. FOXO3 expression was positively correlated with METTL3 expression. METTL3 knockdown significantly reduced FOXO3 mRNA stability and its protein levels in anthracycline-resistant AML cells, which exhibited higher m6A-modified FOXO3 expression levels than their sensitive counterparts. Database analysis, Kaplan-Meier analysis and RT-qPCR results suggested that a high FOXO3 expression was associated with a poor prognosis of AML patients. In anthracycline-resistant AML cells expressing higher FOXO3 levels than the sensitive cells, lentivirus-mediated overexpression of FOXO3 significantly enhanced cell proliferation and suppressed cell apoptosis. Inhibiting autophagy using an autophagy inhibitor (Baf.A1) obviously enhanced the inhibitory effect of adriamycin on resistant AMI cells and cells overexpressing FOXO3. CONCLUSIONS METTL3 promotes FOXO3 expression via m6A modification, and FOXO3-driven autophagy contributes to anthracycline resistance in AML cells by enhancing cell proliferation and suppressing cell apoptosis.
Humans ; Forkhead Box Protein O3/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Drug Resistance, Neoplasm ; Methyltransferases/genetics* ; Autophagy ; Anthracyclines/pharmacology* ; HL-60 Cells ; Apoptosis ; Cell Proliferation ; K562 Cells

Objective This study aims to sort out the rare disease drugs in the China's Second List of Rare Diseases,to provide reference for the management of rare disease drug treatment.Methods Up to December 31,2023,based on the China's Second List of Rare Diseases,we sorted out the drugs approved in China with the drug label,or approved by the U.S.Food and Drug Administration(FDA)and the European Medicines Agency(EMA)for the treatment of the above diseases,and developed the second batch of rare dis-ease drug catalog in China.The accessibility,localization and coverage of the national medical insurance were also analyzed.Results From the point of view of diseases,a total of 37 diseases in the China's Second List of Rare Diseases have drug indications approved in China,and 10 diseases have drugs listed by the U.S.FDA/EMA and approved in China,but for off-label use.From the point of view of drugs,there are 55 drug indications ap-proved for the treatment of the China's Second List of Rare Diseases,and 22 drugs listed in the U.S.FDA/EMA and approved in the China,but for off-label use.Among the above-mentioned drugs with domestic approved rare disease indications or approved numbers,39 drugs have at least one domestic approval number for a dosage form,covering 30 rare diseases;37 drugs used for at least one rare disease are included in the national medical insur-ance catalog and are covered by reimbursement,covering 29 rare diseases.Conclusions The list of rare disease drugs in the China's Second List of Rare Diseases was established.The number of rare disease drugs and covered diseases approved by China and the U.S.FDA/EMA has increased,and the number of rare disease drugs and covered diseases that are localized and included in the medical insurance catalog has also continued to increase.

Objective To summarize and analyze what the listing in market of orphan drugs in China,the United States,the European Union,and Japan in 2023,and to provide empirical reference to Chinese phar-maceutical enterprises,pharmaceutical management,and new drug research and development departments.Methods Collect the 2023 drug market data released by official drug regulatory agencies in four countries and international organization-China,the United States,the European Union,and Japan categorize the market of rare disease drugs and and their indications,approval dates,R&D status in China,component therapeutic are-as,and special review and approval pathways were analyzed.Results Findings in 2023,28 orphan drugs were listed in the United States,mostly anti-tumor related,accounting for 32.1％(9 out of 28);17 orphan drugs were listed in the European Union,anti-tumor related accounting for 47.0％(8 of 17);22 listed in Japan;and 45 listed in China.In 2023,over 70％orphan drugs listed in the European Union and Japan entered the phase of clinical trials/marketing and applications/approved clinical applications in China(86.4％from Japan and 70.6％from European Union).Conclusions Currently,there is no qualification accreditation mechanism for orphan drugs in China.However,in 2023,the number of rare disease drugs listed in China was the greatest among the four countries/international organization.It reflects that China's Catalog for Rare Diseases played a guiding role in drug research and development.Meanwhile,the reform of drug approval and review in China and the issue of rare disease catalogs took place in a short period of time,so the review and approval,as well as re-search and development of rare disease drugs are still in the catching up stage.

Objective To investigate the risk factors of recurrent stroke in IS patients with CHF.Methods A total of 235 elderly IS patients with CHF admitted to Northern Jiangsu People's Hospital from January 2021 to January 2023 were enrolled in this study.According to LVEF clas-sification,they were divided into reduced ejection fraction HF group(HFrEF,LVEF＜40％,80 patients),intermediate ejection fraction HF group(HFmrEF,40％≤LVEF＜50％,57 patients),and preserved ejection fraction HF group(HFpEF,LVEF≥50％,98 patients).After all of them were followed up for 12 months,the patients with recurrent IS were assigned into the recurrent IS group(42 patients)and those without into the non-recurrent IS group(193 patients).Their gener-al data,laboratory results,clinical endpoint events and other indicators were compared in the above groups.Multivariate logistic regression analysis was applied to identify the related risk fac-tors for recurrent stroke in elderly patients with CHF and IS.Results There were significant differences in women ratio,age,history of smoking and drinking,peripheral vascular disease,RBC count,hemoglobin,hematocrit,LDL-C,prothrombin time,international standardized ratio,BNP,LVEF,LVEDD and LVESD among the three groups(P＜0.05,P＜0.01).The recurrent IS group had obviously larger proportion of diabetes mellitus,longer thrombin time,and larger LAD and RAD when compared with the non-recurrent IS group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that diabetes(OR=0.251,95％CI:0.1 96-1.494,P=0.031)and LAD(OR=1.085,95％CI:1.008-1.169,P=0.031)were independent risk factor for recurrent stroke in elderly patients with CHF and IS.There were no significant differences in follow-up period and incidence of clinical endpoints among the three groups(P＞0.05).Conclusion Diabetes and LAD are independent risk factors for recurrent IS in elderly CHF patients with IS.

Objective:To explore the latent profile types of capability-opportunity-motivation-behavior in stroke patients and analyze the influencing factors of different latent profiles.Methods:From January to October 2023, totally 596 stroke patients from the Neurology Department of five ClassⅢ Grade A hospitals in Henan Province were selected by stratified random sampling. The patients were surveyed using a general information questionnaire, the Stroke Prevention Knowledge Questionnaire (SPKQ), the Social Support Rating Scale (SSRS), the WHO's Quality of Life Questionnaire- Brief Version (WHOQOL-BREF), the Short Form Health Belief Model Scale (SF-HBMS), and the Health Promoting Lifestyle ProfileⅡ (HPLPⅡ). Latent profile analysis was used to classify the capability-opportunity-motivation-behavior characteristics of stroke patients, and multiple logistic regression was conducted to explore the influencing factors of different latent profiles.Results:Three latent profiles of capability-opportunity-motivation-behavior in stroke patients were identified, including low capability-opportunity-motivation-behavior with high health beliefs (32.4%, 193/596), moderate capability-opportunity-motivation-behavior with insufficient health beliefs (47.5%, 283/596), and high capability-opportunity-motivation-behavior with lack of social support (20.1%, 120/596). Multiple logistic regression analysis showed that educational level, smoking history, family history, body mass index, and Charlson Comorbidity Index score were influencing factors of different latent profiles ( P<0.05) . Conclusions:Stroke patients exhibit distinct classifications of capability-opportunity-motivation-behavior. Targeted interventions should be conducted based on the characteristics of each category to improve health behavior management outcomes in patients.

Objective:To explore the mediating effect of rumination between self-perceived burden (SPB) and stigma in stroke patients, so as to provide theoretical basis for the development of targeted nursing interventions in clinical practice.Methods:In September 2022, cluster sampling was used to select 1 126 stroke patients admitted to Department of Neurology of five ClassⅢ Grade A hospitals in Henan Province as subjects. General Information Questionnaire, Self-Perceived Burden Scale (SPBS), Stroke Stigma Scale (SSS), and Chinese Version of Event Related Rumination Inventory (C-ERRI) were used to investigate stroke patients. Pearson correlation analysis was used to explore the correlation between SPB, rumination, and stigma. AMOS 28.0 software was used to establish the structural equation model, and Bootstrap method was used to test the mediating effect.Results:A total of 1 126 questionnaires were distributed, and 1 026 valid questionnaires were collected, with a valid response rate of 91.12% (1 026/1 126). SPBS score of 1 026 stroke patients was (28.68±8.32), the SSS score was (40.53±9.48) and the C-ERRI score was (25.43±12.62). Pearson correlation analysis showed that SPB in stroke patients was positively correlated with stigma and rumination ( P<0.01), and rumination was positively correlated with stigma ( P<0.01). Bootstrap mediating effect test showed that rumination partially mediated the relationship between SPB and stigma in stroke patients, accounting for 55.15% of the total effect. Conclusions:SPB of stroke patients both directly affect stigma and indirectly affect stigma through rumination. Clinical nursing workers should promptly evaluate patients' SPB, pay attention to the mediating role of rumination, develop effective psychological intervention programs, implement personalized and targeted nursing measures, relieve patients' stigma, and improve treatment and rehabilitation compliance.

Objective:To understand the research status and hotspots in the field of stroke health management at home and abroad, and to provide insights for stroke health management research in China.Methods:Relevant literature on stroke health management published between 2013 and 2023 was retrieved from the Web of Science Core Collection and China National Knowledge Infrastructure databases. CiteSpace 6.1.R6 was used for the visual analysis of the number of publications, authors, institutions, countries, and keywords.Results:A total of 382 relevant articles were included, with 169 in English and 213 in Chinese. The number of publications on stroke health management showed a fluctuating upward trend. Research hotspots and frontiers in stroke health management mainly focused on telemedicine, big data and "Internet+", primary and secondary prevention, risk prediction models, quality of life, and swallowing disorders. Future research trends may focus on management models for post-stroke swallowing disorders, risk identification, and the role of caregivers in remote rehabilitation interventions.Conclusions:Researchers can refer to the research hotspots and trends shown by the visual analysis, with particular attention to health management models for patients with post-stroke swallowing disorders and issues related to remote intervention rehabilitation.

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.