Retinal degenerative diseases are a group of blinding ocular disorders characterized by progressive and irreversible loss of retinal neural cells. They mainly include age-related macular degeneration and retinitis pigmentosa. At present, there are no curative clinical therapies capable of reversing the disease course. Patients have poor long-term visual prognosis, imposing a heavy public-health burden on families and society. Mesenchymal stem cell(MSC)-derived exosomes, as a novel cell-free therapeutic vector, have emerged as a research hotspot due to their low immunogenicity, no tumorigenic risk, and excellent tissue barrier penetration ability. This review systematically summarizes the core mechanisms of MSC-derived exosomes in regulating immune inflammation, inhibiting apoptosis, and promoting retinal neuroprotection and structural/functional recovery via miRNA and tsRNA, compares the efficacy differences and existing controversies among exosomes from different sources, and outlines the advances in intraocular delivery technologies and engineering modification strategies. Combined with preclinical and clinical data, the current bottlenecks and safety evidence for clinical translation were objectively described. Meanwhile, in view of the heterogeneity among existing studies, this review proposes future directions including standardized preparation and the establishment of efficacy evaluation systems, so as to provide theoretical references for the development of novel therapeutic strategies for retinal degenerative diseases.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE: To explore the effectiveness of posterior single-level osteotomy with 360° release and correction for the treatment of osteoporotic vertebral compression fractures (OVCF) complicated with moderate to severe kyphosis. METHODS: A retrospective analysis was conducted on 11 patients with OVCF complicated with moderate to severe kyphosis between January 2022 and March 2023. There were 4 males and 7 females with an average age of 57 years ranging from 47 to 69 years. The disease duration ranged from 3 to 15 months, with an average of 7 months. Fracture segments included T ₁₁ in 3 cases, T ₁₂ in 5, L ₁ in 2, and L ₂ in 1. The T value of lumbar spine bone density was -5.0 to -2.0, with an average of -3.5. The preoperative neurological function was grade E according to Frankel grading. The Pfirrmann classification of the intervertebral disc above the injured vertebra was grade Ⅲ in 8 cases and grade Ⅳ in 3 cases. All patients underwent posterior single-level osteotomy with 360° release and correction. The operation time, intraoperative blood loss, hospital stay, and postoperative complications were recorded. Thoracolumbar local kyphosis Cobb angle, the mean height of the functional spinal unit (FSU), the sagittal vertical axis (SVA), and the sagittal index (SI) were measured. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were used to evaluate the improvement of pain and function before operation, at 1 month after operation, and at last follow-up. RESULTS: The operation successfully completed in all patients, and there was no obvious complication. The operation time ranged from 100 to 190 minutes, with an average of 153 minutes, and the intraoperative blood loss ranged from 200 to 800 mL, with an average of 468 mL. The length of hospital stay was 8-14 days (mean, 12 days). All patients were followed up 6-24 months, with an average of 12.4 months. At last follow-up, all the 11 patients had bony fusion in the osteotomy area, and there was no displacement or subsidence of the Cage, no complication such as internal fixation failure or pseudarthrosis formation was found. The Cobb angle of local thoracolumbar kyphosis, the mean height of FSU, SVA, and SI significantly improved immediately after operation and at last follow-up when compared with preoperative ones, and the VAS score and ODI also significantly improved at 1 month after operation and at last follow-up ( P<0.05); there was no significant difference in above indexes between the two time points after operation ( P>0.05). CONCLUSION Posterior single-level osteotomy with 360° release and correction is an effective surgical method for treating OVCF complicated with moderate to severe kyphosis, with definite early effectiveness.
Humans ; Kyphosis/etiology* ; Male ; Female ; Osteotomy/methods* ; Middle Aged ; Retrospective Studies ; Aged ; Spinal Fractures/diagnostic imaging* ; Fractures, Compression/diagnostic imaging* ; Osteoporotic Fractures/complications* ; Treatment Outcome ; Lumbar Vertebrae/injuries* ; Thoracic Vertebrae/injuries* ; Operative Time ; Fracture Fixation, Internal/methods*

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To analyze the epidemic trend and spatiotemporal distribution characteristics of pertussis in Shandong Province from 2015 to 2024.Methods:Data on pertussis cases in Shandong Province from 2015 to 2024 were collected from the China Information System for Disease Control and Prevention. The ArcGIS spatiotemporal method was used to analyze the epidemic trend and spatiotemporal distribution characteristics of pertussis, and determine the hotspots of incidence.Results:From 2015 to 2024, 46 172 cases of pertussis were reported in Shandong Province, with an average annual incidence rate of about 4.60/100 000. The reported incidence rate showed an overall upward trend, and in 2024, the reported incidence rate reached the highest level in history (19.20/100 000) since the implementation of children′s planning immunization. The areas with high incidence rates were mainly located in the central and western regions of Shandong Province, including Jinan city, Liaocheng city, Tai′an city, Zibo city, Binzhou city, Jining city, Dezhou city, Zaozhuang city, and Dongying city. The global spatial autocorrelation analysis showed that the Moran′s I index of incidence rate of pertussis in Shandong Province in each year from 2015 to 2024 was >0.00, showing obvious spatial clustering. Local spatial autocorrelation analysis showed that the "high high" clustering areas were mainly distributed in some counties (cities, districts) in the central and western regions of Shandong Province, which were hotspots for pertussis incidence in Shandong Province. The spatial trend surface analysis showed that the annual incidence rate of pertussis in each year basically decreased from west to east. In the early stage of the north-south direction, there was a curved trend of low north-south and high in the middle. In the middle and later stages, the northern part was mostly in a higher position, indicating that the central and western regions were the high-risk areas for pertussis in Shandong Province. Conclusions:The pertussis epidemic in Shandong Province from 2015 to 2024 has obvious spatiotemporal clustering, and the central and western regions are the key areas for pertussis prevention and control.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE: To study the results, re-donation situation and characteristics of single-reagent reactive blood donors who were put into the reentry strategy in Wuhan area, explore the rationality and effectiveness of the current reentry strategy, and provide data support for the improvement of the reentry process of blood donors. METHODS: From January 2020 to December 2023, blood donors who conform the reentry criteria and voluntarily applied for returning to Wuhan Blood Center were tested and the results were analyzed. According to the reentry strategy, serological testing and nucleic acid testing were carried out in parallel, serological testing was performed by ELISA with reagents from two different manufacturers, and the primary reactive samples were tested by double-well retest, and HBV/HCV/HIV nucleic acid detection was performed by RT-PCR with an individual donor test mode. Supplementary HBcAb testing was applied for HBV single reagent reactivity by chemiluminescence method. Supplementary TP-WB testing was applied for returning blood donors with repeated TP single reagent reactivity. If returning blood donors with HIV single reagent reactivity were repeated single reagent reactivity, the samples were sent to local CDC for confirmatory test. RESULTS: 7 098 blood donors were qualified for reentry, 716 donors voluntarily applied for reentry, 436 donors successfully reentry, 251 donors entered the next round, 29 donors could not reentry. The reentry rates for the past four years were 66.67%（42/63）, 54.73%（81/148）, 60.71%（136/224） and 62.99%（177/281）, respectively. Up to December 31, 2023, 275 donors donated blood again, and the donation rates for past four years were 76.19%（32/42）, 72.84%（59/81）, 61.76%（84/136） and 56.50%（100/177）, respectively. After donating blood, 31 donors were disqualified again by blood screening and subjected to permanent deferral. The results of returning to the team had statistical differences in reentry items, educational level, age, and marriage（P < 0.05）. CONCLUSION The current reentry strategy adopted by the blood donation and supply institution can effectively retain part of blood donors, reduce the negative emotions of blood donors and increase blood resources.
Humans ; Blood Donors ; China ; Hepatitis B ; Enzyme-Linked Immunosorbent Assay ; Hepatitis C ; Male

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic