BackgroundAlcohol dependence patients are prone to relapse after their attempts to quit drinking， which poses a considerable threat to their physical and mental health and creates a heavy burden on their families. Currently， empowerment education is increasingly being utilized in the rehabilitation management of chronic diseases， but there remains a striking lack of empirical research on the application of "Internet +" empowerment education based on timing it right in alcohol dependence patients. ObjectiveTo explore the impact of "Internet +" empowerment education based on timing it right on patients with alcohol dependence， in order to maximize the reduction in relapse rates， craving for alcohol and severity of anxiety symptoms. MethodsA total of 120 patients who were hospitalized in the Department of Addiction Medicine， Hebei Provincial Mental Health Center from May 2022 to April 2023 and met the diagnostic criteria for alcohol dependence in the International Classification of Diseases， tenth edition （ICD-10） were enrolled， and they were classified into study group （n=62） and control group （n=58） using random number table methods. Both groups received standard medication and routine care. Additionally， study group underwent a 6-month "Internet +" empowerment education based on timing it right. At baseline， all subjects were assessed using Penn Alcohol Craving Scale （PACS） and Self-rating Anxiety Scale （SAS）. Three months and six months after intervention， assessments were conducted using PACS， SAS and Michigan Alcoholism Screening Test （MAST）. ResultsThe relapse rates after three and six months of intervention were both lower in study group than those in control group， with statistically significant differences （χ²=8.575， 8.828， P<0.01）. ANOVA with repeated measures on PACS total score and scores of each item revealed a significant time effect， group effect and time×group interaction effect （F=159.714~837.751， 84.645~393.606， 24.302~137.896， P<0.01）. And significant time effect， group effect and time×group interaction effect were also reported on SAS scores （F=166.237， 65.325， 24.724， P<0.01）. Conclusion"Internet +" empowerment education based on timing it right may help reduce relapse rates， alcohol cravings and severity of anxiety symptoms among patients with alcohol dependence. ［Funded by 2023 Annual Hebei Provincial Medical Scientific Research Project Plan （number， 20231537）］

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Objective To compare the efficacy of modified radiofrequency ablation (RFA) combined with sclerosing agent injection and high stripping and ligation (HSL) combined with sclerosing agent injection in the treatment of great saphenous vein varicosity. Methods A total of 220 patients (252 affected limbs) who underwent surgery for great saphenous vein varicosity at Affiliated Hospital of Nantong University from May 2022 to March 2024 were selected. They were divided into RFA group (110 patients and 125 affected limbs treated with modified RFA combined with sclerosing agent injection) and HSL group (110 patients and 127 affected limbs treated with HSL combined with sclerosing agent injection) according to the surgical methods. The treatment effect, surgical time, bleeding during the surgery, time to get out of bed after surgery, and various postoperative complications were compared between the two groups. The pain level, disease severity, and the quality of life were measured using the visual analog scale (VAS), venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire-14 item (CIVIQ-14), respectively. Results There was no statistically significant difference in the total effective rate between the two groups of patients, but the distribution of efficacy levels in the RFA group was better than that in the HSL group (P＝0.044). Compared with the HSL group, the RFA group had shorter surgery time, fewer incisions during surgery, less bleeding during the surgical process, shorter time to get out of bed after surgery（P＜0.01）, and a lower overall complication rate (P＝0.006). The RFA group had lower postoperative VAS, VCSS, and CIVIQ-14 scores than the HSL group 1 month after surgery (P＜0.01). During 6 months of postoperative follow-up, the recurrence rates were similar between the two groups. Conclusions Compared with HSL combined with sclerosing agent injection, the modified RFA combined with sclerosing agent injection for the great saphenous vein varicosity has the advantages of less trauma, faster recovery, fewer complications, better postoperative quality of life, and is worthy of clinical promotion and application.

OBJECTIVE: To develop a clinical automated diagnostic system for temporomandibular disorders (TMD) based on the diagnostic criteria for TMD (DC/TMD) to assist dentists in making rapid and accurate clinical diagnosis of TMD. METHODS: Clinical and imaging data of 354 patients, who visited the Center for TMD & Orofacial Pain at Peking University Hospital of Stomatology from September 2023 to January 2024, were retrospectively collected. The study developed a clinical automated diagnostic system for TMD using the DC/TMD, built on the. NET Framework platform with branching statements as its internal structure. Further validation of the system on consistency and diagnostic efficacy compared with DC/TMD were also explored. Diagnostic efficacy of the TMD clinical automated diagnostic system for degenerative joint diseases, disc displacement with reduction, disc displacements without reduction with limited mouth opening and disc displacement without reduction without limited mouth opening was evaluated and compared with a specialist in the field of TMD. Accuracy, precision, specificity and the Kappa value were assessed between the TMD clinical automated diagnostic system and the specialist. RESULTS: Diagnoses for various TMD subtypes, including pain-related TMD (arthralgia, myalgia, headache attributed to TMD) and intra-articular TMD (disc displacement with reduction, disc displacement with reduction with intermittent locking, disc displacement without reduction with limited opening, disc displacement without reduction without limited opening, degenerative joint disease and subluxation), using the TMD clinical automated diagnostic system were completely identical to those obtained by the TMD specialist based on DC/TMD. Both the system and the expert showed low sensitivity for diagnosing degenerative joint disease (0.24 and 0.37, respectively), but high specificity (0.96). Both methods achieved high accuracy (> 0.9) for diagnosing disc displacements with reduction and disc displacements without reduction with limited mouth opening. The sensitivity for diagnosing disc displacement without reduction without limited mouth opening was only 0.59 using the automated system, lower than the expert (0.87), while both had high specificity (0.92). The Kappa values for most TMD subtypes were close to 1, except the disc displacement without reduction without limited mouth opening, which had a Kappa value of 0.68. CONCLUSION This study developed and validated a reliable clinical automated diagnostic system for TMD based on DC/TMD. The system is designed to facilitate the rapid and accurate diagnosis and classification of TMD, and is expected to be an important tool in clinical scenarios.
Humans ; Temporomandibular Joint Disorders/diagnosis* ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; Facial Pain/diagnosis* ; Diagnosis, Computer-Assisted/methods* ; Sensitivity and Specificity ; Young Adult

The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.
Humans ; Lysosomes/physiology* ; Autophagy/physiology* ; Nanomedicine/methods* ; Neurodegenerative Diseases/therapy* ; Animals ; Nanostructures ; Lysosomal Storage Diseases/therapy*

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Objective To observe the effects of Jianpi Qutan Huayu Prescription on oxidative stress and inflammatory response in mini-pigs with atherosclerosis(AS);To explore its mechanism based on the NOX5-ERK1/2 signaling pathway.Methods Twelve Bama mini-pigs were randomly divided into control group,model group,and Jianpi Qutan Huayu Prescription low-and high-dosage groups,with 3 pigs in each group.A high-fat diet was used to feed for 24 weeks to construct an AS model,and the treatment group was also supplemented with Jianpi Qutan Huayu Prescription in the feed.The general condition of mini-pigs(body length,abdominal circumference,body mass,food intake,and fecal water content)was measured at week 0,16,and 24 of administration,HE staining was used to observe the morphology of aortic tissue,while oil red O staining was used to observe lipid deposition in aortic and myocardial tissue,transmission electron microscopy was used to observe the ultrastructure of aortic tissue,and a fully automated biochemical analyzer was used to detect serum contents of TC,HDL-C,and LDL-C.ELISA was used to detect the contents of serum reactive oxygen species(ROS),interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,hypersensitivity-C-reactive protein(hs-CRP),vascular cell adhesion molecule-1(VCAM-1),and intercellular adhesion molecule-1(ICAM-1).Western blot was used to detect the expressions of NADPH oxidase 5(NOX5),extracellular signal regulated kinase 1/2(ERK1/2),p-ERK1/2,VCAM-1,and proliferating cell nuclear antigen(PCNA)proteins.Results Compared with the control group,the abdominal circumference,body mass,and food intake of mini-pigs in the model group increased at 16 and 24 weeks(P<0.01),there was significant thickening of the inner membrane of aorta,destruction of endothelial cells,lipid deposition,edema of smooth muscle cells,and significant swelling of mitochondria,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,VCAM-1,and ICAM-1 increased,while the content of HDL-C decreased(P<0.01);the expressions of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue increased(P<0.01).Compared with the model group,Jianpi Qutan Huayu Prescription low-and high-dosage groups showed a decrease in abdominal circumference,body mass,and food intake at 16 and 24 weeks(P<0.05,P<0.01),the plaque area and lipid deposition were reduced,and the damage to endothelial cells was alleviated,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,ICAM-1,and VCAM-1 decreased,and the content of HDL-C increased(P<0.01,P<0.05);the expressiond of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue decreased(P<0.01,P<0.05).Conclusion Jianpi Qutan Huayu Prescription can effectively alleviate AS in mini-pigs,and its mechanism may be related to inhibiting the activation of the NOX5-ERK1/2 signaling pathway and alleviating oxidative stress-induced inflammatory response.

Objective:To explore the clinical efficacy and safety of daratumumab-based combined regimens for relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. The clinical data of 38 patients with RRMM in Jining NO.1 People's Hospital from Janunary 2020 to December 2022 were retrospectively analyzed. All patients were treated with daratumumab-based combined regimens. The Dd regimen (12 cases) was treated with daratumumab and dexamethasone, the DPD regimen (20 cases) was treated with pomalodomide based on the Dd regimen, the DVD regimen (6 cases) was treated with bortezomib based on the Dd regimen. The therapeutic efficacy and adverse reactions of all groups were analyzed. Kaplan-Meier method was used for survival analysis.Results:The median follow-up time was 9.5 months (1.0 months, 32.5 months) and the median treatmemt time was 6.2 months (3.2 months, 25.6 months). Among 38 patients, 7 cases (18.7%) achieved complete remission, 9 cases (23.6%) achieved very good partial remission, 10 cases (26.3%) achieved partial remission, 4 cases (10.5%) achieved minimal remission, 5 cases (13.1%) achieved stable disease, 3 cases (7.9%) had the progression of the disease. The overall response rate (ORR) was 78.9% (30/38). The ORR was 66.7%(8/12), 83.3%(5/6), 85.0%(17/20), respectively in the Dd group, DVD group and DPD group. There was no statistically significant difference in the ORR between the DVD group and DPD group ( χ2 = 0.01, P>0.05); there was no statistically significant difference in the ORR between the DVD group and Dd group ( χ2 = 0.55, P>0.05); there was no statistically significant difference in the ORR between the DPD group and Dd group ( χ2 = 1.47, P>0.05). The median progression-free survival (PFS) time was 12.5 months (95% CI: 8.5-24.2 months),the median overall survival (OS) time was not reached, and the 1-year OS rate was 89.4%. Among 38 patients, the main adverse reactions during treatment were infusion-related adverse reactions in 5 cases, grade 3 neutropenia in 7 cases, grade 3 thrombocytopenia in 9 cases, severe anemia in 12 cases; no one had drug discontinuation or drug reduction due to the intolerance of adverse reactions. Conclusions:Daratumumab-based combined regimens in the treatment of RRMM show a favorable efficacy and safety.

Objective:To investigate the clinical efficacy of labial mucosa graft coupled preputial island flap urethroplasty for recurrent penile curvature after hypospadias repair.Methods:The data of 35 patients with recurrent penile curvature after hypospadias repair who underwent labial mucosa graft coupled preputial island flap urethroplasty in four hospitals from January 2021 to March 2023 were retrospectively reviewed. The median age of the patients was 15(13, 18)years old, five of them had penile dehiscence, and four had urethrocutaneous fistula. All patients received labial mucosa graft coupled preputial island flap urethroplasty, the penile flexion was confirmed by artificial erection test, and the urethra is obliquely cut at the most obvious curvature of the penis. By removing the ventral fibrotic scar tissue, the length of the urethral defect was measured. The urethral plate was reconstructed with the same length of labial mucosa graft and an adjacent preputial island flap was transplanted to cover the reconstructed urethra plate to form a new urethral lumen. The inner urethral stent tube was extracted three days after the operation, and the outer urethral stent tube was removed three weeks after the surgery. Diagnostic urethral exploration was performed 5 weeks post-operation, uroflowmetry examination was performed seven weeks after the procedure, and the perioperative and postoperative follow-up data were analyzed.Results:All patients underwent a successful surgery, with the average duration of the procedure being (114.7±20.1)minutes. After mean follow-up of (15.5±5.9)months, no penile curvature occurred, and 32 patients were successfully repaired. Uroflowmetry examination was achieved in 21 patients at the seventh week after surgery showed their mean maximum flow rate was (18.4±3.7)ml/s. Three cases (8.6%, 3/35) developed urethrocutaneous fistula, who were repaired successfully 6 months after surgery.Conclusions:Utilizing the combination of labial mucosa grafts and preputial island flaps for urethroplasty has been proven to be a reliable and safe option for individuals with recurrent penile curvature following hypospadias repair, with a high success rate and few complications.