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Shwu-Jiuan Sheu,1,2 Cheng-Kuo Cheng,3,4 Hsi-Kung Kuo,5 Ching-Yao Tsai,2,6 Tai-Chi Lin,2,7 Jonathan Tan,8 Hitesh Chandwani,8 Michael Adena,9 Shih-Jen Chen2,7 1Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Department of Ophthalmology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Ophthalmology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 4Department of Medicine, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; 5Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 6Department of Ophthalmology, Taipei City Hospital Zhongxing Branch, Taipei, Taiwan; 7Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; 8Global Health Economics and Outcomes Research, Allergan Singapore Pte. Ltd., Singapore, Singapore; 9Datalytics Pty Ltd, Kingston, ACT, Australia Objectives: To characterize diabetic macular edema (DME) treatment patterns in Taiwan and examine their impact on health care resource utilization and visual and anatomic outcomes. Methods: Retrospective, observational cohort study of longitudinal data from medical records of five hospital ophthalmology clinics. Patients with type 2 diabetes and DME who received ≥1 laser treatment or pharmacotherapy (intravitreal/subtenon corticosteroids and/or intravitreal anti-vascular endothelial growth factor [VEGF] agents) between January 2012 and December 2013 (index period) and attended ≥1 follow-up visit after the first treatment during that period were identified (prevalent population, N=431). In addition, a subset that received no anti-VEGFs before 2012 (anti-VEGF-naïve population, N=77) was analyzed. Outcome measures were change in DME treatment distribution between January 2009 and December 2014 and health care resource utilization over up to 3 years from the first DME treatment received in the index period (prevalent population), mean number of anti-VEGF injections and change from baseline in visual acuity and central macular thickness over 12 months (anti-VEGF-naïve population).Results: Between 2009 and 2014, laser treatment use declined, overall use of anti-VEGFs increased, and bevacizumab use decreased proportionately as ranibizumab use increased. Patients receiving corticosteroids and anti-VEGFs in the first 6 months post-index had greater health care resource utilization than those treated with laser, corticosteroids, or anti-VEGF alone (P

There is a need to monitor patients with cancer of the head and neck postradiation therapy, as diminished swallowing activity can result in disuse atrophy and fibrosis of the swallowing muscles. This paper describes a flexible strain sensor comprising palladium nanoislands on single-layer graphene. These piezoresistive sensors were tested on 14 disease-free head and neck cancer patients with various levels of swallowing function: from nondysphagic to severely dysphagic. The patch-like devices detected differences in (1) the consistencies of food boluses when swallowed and (2) dysphagic and nondysphagic swallows. When surface electromyography (sEMG) is obtained simultaneously with strain data, it is also possible to differentiate swallowing vs nonswallowing events. The plots of resistance vs time are correlated to specific events recorded by video X-ray fluoroscopy. Finally, we developed a machine-learning algorithm to automate the identification of bolus type being swallowed by a healthy subject (86.4%. accuracy). The algorithm was also able to discriminate between swallows of the same bolus from either the healthy subject or a dysphagic patient (94.7% accuracy). Taken together, these results may lead to noninvasive and home-based systems for monitoring of swallowing function and improved quality of life.

Background: The transition from the vegetative mycelium to the primordium during fruiting body development is the most complex and critical developmental event in the life cycle of many basidiomycete fungi. Understanding the molecular mechanisms underlying this process has long been a goal of research on basidiomycetes. Large scale assessment of the expressed transcriptomes of these developmental stages will facilitate the generation of a more comprehensive picture of the mushroom fruiting process. In this study, we coupled 5'-Serial Analysis of Gene Expression (5'-SAGE) to high-throughput pyrosequencing from 454 Life Sciences to analyze the transcriptomes and identify up-regulated genes among vegetative mycelium (Myc) and stage 1 primordium (S1-Pri) of Coprinopsis cinerea during fruiting body development.Results: We evaluated the expression of >3,000 genes in the two respective growth stages and discovered that almost one-third of these genes were preferentially expressed in either stage. This identified a significant turnover of the transcriptome during the course of fruiting body development. Additionally, we annotated more than 79,000 transcription start sites (TSSs) based on the transcriptomes of the mycelium and stage 1 primoridum stages. Patterns of enrichment based on gene annotations from the GO and KEGG databases indicated that various structural and functional protein families were uniquely employed in either stage and that during primordial growth, cellular metabolism is highly up-regulated. Various signaling pathways such as the cAMP-PKA, MAPK and TOR pathways were also identified as up-regulated, consistent with the model that sensing of nutrient levels and the environment are important in this developmental transition. More than 100 up-regulated genes were also found to be unique to mushroom forming basidiomycetes, highlighting the novelty of fruiting body development in the fungal kingdom.Conclusions: We implicated a wealth of new candidate genes important to early stages of mushroom fruiting development, though their precise molecular functions and biological roles are not yet fully known. This study serves to advance our understanding of the molecular mechanisms of fruiting body development in the model mushroom C. cinerea. © 2013 Cheng et al.; licensee BioMed Central Ltd.

Purpose: Implantation of prosthetic tibio-femoral components in hyperextension is a well-established and effective procedure, but whether prosthetic orientation in the sagittal plane has any effects on the postoperative kinematics remains unclear. The purpose of this study is to explore how the aforementioned hyperextension affects knee kinematics.Methods: Validated computational dynamic TKA models were established. Based on representative literatures and actual operation specifications, femoral and tibial components were assembled with 0° or 5° of hyperextension. Dynamic data, including the timing of cam-post engagement, anterioposterior femoral translation and tibial axial rotation coupling with knee flexion, were recorded for analysis.Results: 5° of femoral component hyperextension delayed cam-post engagement by an angle of 2°. Nevertheless, a 5° posterior slope of the tibial component resulted in a 38° delay in engagement. Comparing this with the femoral component at the same angle of hyperextension, the tibial component could more evidently assist in the prevention of paradoxical femoral anterior translation and the promotion of tibial internal rotation through early flexion.Conclusion: Tibio-femoral components in hyperextension did significantly alter postoperative kinematics, especially for the tibial component. These results suggest that the degree of tibial posterior slope cutting should be more highly scrutinized intraoperatively.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: In vitro and in vivo studies to assess the effect of direct anular repair on subsequent degeneration of intervertebral discs (IVDs). OBJECTIVE: To assess whether a new suturing method could provide sealing effect on IVD after discectomy, and influence degenerative process of IVD. SUMMARY OF BACKGROUND DATA: Recurrent disc herniation and subsequent disc degeneration are major problems after discectomy. Anular repair can reduce the risk of recurrence, but its effect on disc degeneration needs more investigation. METHODS: A new suturing technique, the modified purse-string suture (MPSS), was designed for direct closure of anular incision. Intact motion segments of porcine lumbar spine were used to validate this technique in resisting disc pressure under mechanical loadings. A transverse slit incision was made in the anterior anulus of porcine cervical discs, with or without sealing of the anular defect by this suturing method. Magnetic resonance imaging grading was recorded before and after surgery. Anular healing was assessed histologically and gene expression of aggrecan, collagen type I, II, and matrix metalloproteinase-13 in nucleus pulposus were investigated. RESULTS: The average failure force of axial compression was 1150.3 ± 121.1 N for a simple suture, and 2917.9 ± 627.6 N for a MPSS. Cyclic loading test showed that the repaired discs succeeded against repeated compression forces. Magnetic resonance imaging and gross appearances showed lesser degenerative changes in repaired discs than in injured discs at each time period. In repaired discs, mRNA expression of aggrecan and type II collagen downregulated slightly with time, whereas it decreased rapidly and persistently in unrepaired discs. Histologic findings showed primary healing of outer anular tract in repaired discs. CONCLUSION: In this pilot study, the MPSS can provide effectively sealing for damaged anulus to withstand stresses. Direct repair of anular incision by this suturing method does significantly slow down degenerative process within discs after discectomy. [ABSTRACT FROM AUTHOR]

Background: Few data are available about the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission.Objective: To investigate whether hand hygiene and use of facemasks prevents household transmission of influenza.Design: Cluster randomized, controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment. (ClinicalTrials.gov registration number: NCT00425893)Setting: Households in Hong Kong.Patients: 407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households.Intervention: Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members.Measurements: Influenza virus infection in contacts, as confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days.Results: Sixty (8%) contacts in the 259 households had RT-PCR-confirmed influenza virus infection in the 7 days after intervention. Hand hygiene with or without facemasks seemed to reduce influenza transmission, but the differences compared with the control group were not significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR-confirmed infection seemed reduced, an effect attributable to fewer infections among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 [95% CI, 0.13 to 0.87]). Adherence to interventions varied.Limitation: The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness.Conclusion: Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza.Primary Funding Source: Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the dimensional alterations in the anterior region of the orbit after enucleation or evisceration. Materials and Methods: Analysis of orbital areas and perimeters of 17 patients with unilateral removal of the ocular bulb was performed, and posteroanterior radiographic examination was carried out by a single specialist, who had been previously calibrated. Results: Data obtained from measurements confirmed the clinically observed facial asymmetry. Conclusion: The observation of asymmetry in the anterior orbital area, confirmed by our results, indicates early treatment to prevent orbital disturbances and will aid in the planning of prosthetic rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Influenza surveillance systems provide important and timely information to health service providers on trends in the circulation of influenza virus and other upper respiratory tract infections. Online dissemination of surveillance data is useful for risk communication to health care professionals, the media and the general public. We reviewed national influenza surveillance websites from around the world to describe the main features of surveillance data dissemination.Methods: We searched for national influenza surveillance websites for every country and reviewed the resulting sites where available during the period from November 2008 through February 2009. Literature about influenza surveillance was searched at MEDLINE for relevant hyperlinks to related websites. Non-English websites were translated into English using human translators or Google language tools.Results: A total of 70 national influenza surveillance websites were identified. The percentage of developing countries with surveillance websites was lower than that of developed countries (22% versus 57% respectively). Most of the websites (74%) were in English or provided an English version. The most common surveillance methods included influenza-like illness consultation rates in primary care settings (89%) and laboratory surveillance (44%). Most websites (70%) provided data within a static report format and 66% of the websites provided data with at least weekly resolution.Conclusion: Appropriate dissemination of surveillance data is important to maximize the utility of collected data. There may be room for improvement in the style and content of the dissemination of influenza data to health care professionals and the general public. [ABSTRACT FROM AUTHOR]

Aging, an independent risk factor for cardiometabolic diseases, refers to a progressive deterioration in physiological function, characterized by 12 established hallmarks. Vascular aging is driven by endothelial dysfunction, telomere dysfunction, oxidative stress, and vascular inflammation. This study investigated whether aged gut microbiome promotes vascular aging and metabolic impairment. Fecal microbiome transfer (FMT) was conducted from aged (>75 weeks old) to young C57BL/6 mice (8 weeks old) for 6 weeks. Wire myography was used to evaluate endothelial function in aortas and mesenteric arteries. ROS levels were measured by dihydroethidium (DHE) staining and lucigenin-enhanced chemiluminescence. Vascular and intestinal telomere function, in terms of relative telomere length, telomerase reverse transcriptase expression and telomerase activity, were measured. Systemic inflammation, endotoxemia and intestinal integrity of mice were assessed. Gut microbiome profiles were studied by 16S rRNA sequencing. Some middle-aged mice (40-42 weeks old) were subjected to chronic metformin treatment and exercise training for 4 weeks to evaluate their anti-aging benefits. Six-week FMT impaired glucose homeostasis and caused vascular dysfunction in aortas and mesenteric arteries in young mice. FMT triggered vascular inflammation and oxidative stress, along with declined telomerase activity and shorter telomere length in aortas. Additionally, FMT impaired intestinal integrity, and triggered AMPK inactivation and telomere dysfunction in intestines, potentially attributed to the altered gut microbial profiles. Metformin treatment and moderate exercise improved integrity, AMPK activation and telomere function in mouse intestines. Our data highlight aged microbiome as a mechanism that accelerates intestinal and vascular aging, suggesting the gut-vascular connection as a potential intervention target against cardiovascular aging and complications.

Background: The present study aimed to identify the risk factors of periprosthetic femoral fracture (PFF) after cementless total hip arthroplasty and rank them based on importance., Methods: The age, sex, body mass index (BMI), osteoporosis, canal flare index (CFI), canal bone ratio (CBR), canal calcar ratio (CCR), stem design, and stem canal fill ratio (P1, P2, P3, and P4) of the proximal femoral medullary cavity of 111 total hip arthroplasty patients who had PFF and 388 who did not have PFF were analyzed. Independent-samples student t-tests were used for continuous variables, and Chi-square tests were used for categorical variables. The importance rankings of influencing factors were assessed using a random forest algorithm. Dimensionally reduced variables were then incorporated into a binary logistic regression model to determine the PFF-related risk factors., Results: The mean age, BMI, CBR, CCR, and incidence of osteoporosis were higher in cases of PFF (all P < .001), while the mean CFI, P1, P2, P3, and P4 were lower in cases of PFF (P < .001, P = .033, P = .008, P < .001, and P < .001, respectively). Additionally, the stem design was also statistically associated with PFF (P < .001). Multivariate logistic regression revealed that advanced age, higher BMI, osteoporosis, stem design, lower CFI, higher CBR, higher CCR, lower P1, lower P2, lower P3, and lower P4 were the risk factors of PFF (P < .001, P < .001, P < .001, P < .001, P < .001, P = .010, P < .001, P = .002, P < .001, P < .001, and P = .007, respectively). The ranked importance of the risk factors for PFF was P3, CFI, osteoporosis, CBR, age, P4, P1, stem design, CCR, BMI, and P2., Conclusions: Lower P3, lower CFI, osteoporosis, higher CBR, advanced age, lower P4, lower P1, stem design, higher CCR, higher BMI, and lower P2 increased the risk of PFF., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

After tendon or ligament reconstruction, the interface between the hard bone and soft connective tissue is considerably weakened and is difficult to restore through healing. The tendon/ligament-bone interface is mechanically the weakest point under tensile loading and is often the source of various postoperative complications, such as bone resorption and graft laxity. A comprehensive understanding of the macro- and microfeatures of the native tendon/ligament-bone interface would be beneficial for developing strategies for regenerating the tissue. This article discusses the structural, biological, and mechanical features of the tendon/ligament-bone interfaces and how these can be affected by aging and loading conditions.

Background Context: Large annulus fibrosus (AF) defects often lead to a high rate of reherniation, particularly in the medial AF region, which has limited self-healing capabilities. The increasing prevalence of herniated discs underscores the need for effective repair strategies., Purpose: The objectives of this study were to design an AF repair technique to reduce solve the current problems of insufficient mechanical properties and poor sealing capacity., Study Design: In vitro biomechanical experiments and finite element analysis., Methods: The materials used in this study were patches and hydrogels with good biocompatibility and sufficient mechanical properties to withstand loading in the lumbar spine. Five repair techniques were assessed in this study: hydrogel filler (HF), AF patch medial barrier (MB), AF patch medial barrier and hydrogel filler (MB&HF), AF patch medial-lateral barrier (MLB), and AF patch medial-lateral barrier and hydrogel filler (MLB&HF). The repair techniques were subjected to in vitro testing (400 N axial compression and 0-500 N fatigue loading at 5Hz) and finite element analysis (400 N axial compression) to evaluate the effectiveness at repairing large AF defects. The evaluation included repair tightness, spinal stability, and fatigue resistance., Results: From the in vitro testing, the failure load of the repair techniques was in the following order HF MLB >MB&HF >MLB&HF., Conclusions: The combined use of patches and hydrogels exhibited promising mechanical properties postdiscectomy, providing a promising solution for addressing large AF defects and improving disc stability., Clinical Significance: This study introduces a promising method for repairing large annular fissure (AF) defects after disc herniation, combining patch repair with a hydrogel filler. These techniques hold potential for developing clinical AF repair products to address this challenging issue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As the innermost monolayer of the vasculature, endothelial cells (ECs) serve as the interface for multiplex signal transduction. Directly exposed to blood-borne factors, both endogenous and exogenous, ECs actively mediate vascular homeostasis and represent a therapeutic target against cardiometabolic diseases. ECs act as the first-line gateway between gut-derived substances and vasculature. Additionally, ECs convert blood flow-exerted hemodynamic forces into downstream biochemical signaling to modulate vascular pathophysiology. Besides, ECs can sense other forms of stimuli, like cell extrusion, thermal stimulation, photostimulation, radiation, magnetic field, noise, and gravity. Future efforts are still needed to deepen our understanding on endothelial biology., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Topic: To systematically compare the effectiveness of conventional phacoemulsification surgery (CPS) and low-energy femtosecond laser-assisted cataract surgery (FLACS) in patients with cataract., Clinical Relevance: Cataract surgery is a common procedure, and comparing different techniques such as CPS and low-energy FLACS is crucial for optimizing patient outcomes., Methods: The PubMed, Web of Science, MEDLINE, EMBASE, and Cochrane library databases were searched for clinical trials. Outcomes of procedure time, effective phacoemulsification time, balanced salt solution usage, cumulative dissipated energy, mean change of corrected distance visual acuity, endothelial cells reduction, central corneal thickness (CCT), and aqueous cytokine level were evaluated. The effect measures were weighted mean differences with 95% CI. The protocol was registered at the Prospective Register for Systematic Reviews (registration number CRD42023420173)., Results: 11 studies were included in this meta-analysis, of which 1680 eyes were analyzed (637 eyes in the low-energy FLACS group and 1043 eyes in the CPS group). Low-energy FLACS demonstrated significantly fewer reductions in endothelial cell count at 6 months ( P < .001) compared with CPS. It also exhibited a shorter effective phacoemulsification time ( P < .001) and less balanced salt solution usage ( P < .001). However, there were no differences in cumulative dissipated energy, corrected distance visual acuity, CCT changes, or aqueous cytokine levels between the 2 groups., Conclusions: Both low-energy FLACS and CPS are effective in treating cataracts, but low-energy FLACS may offer advantages such as reduced phacoemulsification time and less endothelial cell loss., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: The fracture of bone plate can cause considerable pain for the patient and increase the burden on the public finances. This study aims to explore the failure mechanism of 49 plates retrieved from revision surgery and introduce pure magnesium (Mg) block to improve the biomechanical performance of the plate via decreasing the stiffness and to stimulate the biological response of the plate potentially by the degradation of Mg block., Methods: The morphological analysis and component analysis of the plates were conducted to determine the fracture reason of the plates combining the clinical data. According to the structural feature, the 49 retrieved plates were divided into: traditional plate (TP), asymmetrical plate (AP), reconstructive plate (RP) and central enhancement plate (CEP), and their structure features are normalized in a commercial plate, respectively. The biomechanical performance of the plates was evaluated using a validated femoral finite element model. A block of pure Mg with a thickness of 1 mm, 1.5 mm and 2 mm was also incorporated into the CEP to be assessed., Results: The results indicated that the retrieved plates mainly failed due to fatigue fracture induced by delayed union or nonunion (44/49), and using pure titanium plates in weight-bearing areas increased the risk of fracture compared with Ti alloy plates when the delayed union or nonunion occurred. The TP demonstrated the highest compression resistance and bending resistance, while CEP had the highest rotational resistance. As the thickness of the Mg block was increased, the stress on the plate in compression decreased, but the stress in rotation increased. The plate with a 1.5 mm Mg block demonstrated excellent compression resistance, bending resistance and rotational resistance., Conclusion: Fatigue fracture resulting from the delayed union or nonunion is the primary failure reason of plates in clinic. The incorporation of Mg block into plate improves the biomechanical performance and has the potential to promote bone healing. The plate with a 1.5 mm Mg block may be suitable for use in orthopaedics., The Translational Potential of This Article: This study assessed the failure mechanism of retrieved bone plates and used this data to develop a novel plate incorporating a 1.5 mm block of pure Mg block at the position corresponding to the fracture line. The novel plate exhibited excellent compression resistance, bending resistance and rotational resistance due to the alleviation of stress concentrations. The Mg block has the potential to degrade over time to promote fracture healing and prevents fatigue fracture of plates., Competing Interests: A conflict of interest occurs when an individual's objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. The Editors of the Journal of Orthopaedic Translation strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distinguish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to disclose all and any potential conflicts of interest., (© 2024 The Authors.)

Introduction: In de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real-world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes., Methods: A prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6-months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders., Findings: A total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression-free survival (HR = 0.56; 95%CI = 0.34-0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26-0.97; p = 0.036), and cancer-specific survival (HR = 0.43; 95%CI = 0.19-0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis., Conclusion: Our analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real-world setting, providing valuable information for patient counselling and potentially guiding future trial design., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Inflammatory diseases compromise a clinically common and diverse group of conditions, causing detrimental effects on body functions. Gasdermins (GSDM) are pore-forming proteins, playing pivotal roles in modulating inflammation. Belonging to the GSDM family, gasdermin D (GSDMD) actively mediates the pathogenesis of inflammatory diseases by mechanistically regulating different forms of cell death, particularly pyroptosis, and cytokine release, in an inflammasome-dependent manner. Aberrant activation of GSDMD in different types of cells, such as immune cells, cardiovascular cells, pancreatic cells and hepatocytes, critically contributes to the persistent inflammation in different tissues and organs. The contributory role of GSDMD has been implicated in diabetes mellitus, liver diseases, cardiovascular diseases, neurodegenerative diseases, and inflammatory bowel disease (IBD). Clinically, alterations in GSDMD levels are potentially indicative to the occurrence and severity of diseases. GSDMD inhibition might represent an attractive therapeutic direction to counteract the progression of inflammatory diseases, whereas a number of GSDMD inhibitors have been shown to restrain GSDMD-mediated pyroptosis through different mechanisms. This review discusses the current understanding and future perspectives on the role of GSDMD in the development of inflammatory diseases, as well as the clinical insights of GSDMD alterations, and therapeutic potential of GSDMD inhibitors against inflammatory diseases. Further investigation on the comprehensive role of GSDM shall deepen our understanding towards inflammation, opening up more diagnostic and therapeutic opportunities against inflammatory diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cheng, Yi, Wang and Huang.)

Background : Total joint arthroplasty (TJA) is an orthopedic procedure commonly used to treat damaged joints. Despite the efficacy of TJA, postoperative complications, including aseptic prosthesis loosening and infections, are common. Moreover, the effects of individual genetic susceptibility and modifiable risk factors on these complications are unclear. This study analyzed these effects to enhance patient prognosis and postoperative management. Methods : We conducted an extensive genome-wide association study (GWAS) and Mendelian randomization (MR) study using UK Biobank data. The cohort included 2964 patients with mechanical complications post-TJA, 957 with periprosthetic joint infection (PJI), and a control group of 398,708 individuals. Genetic loci associated with postoperative complications were identified by a GWAS analysis, and the causal relationships of 11 modifiable risk factors with complications were assessed using MR. Results : The GWAS analysis identified nine loci associated with post-TJA complications. Two loci near the PPP1R3B and RBM26 genes were significantly linked to mechanical complications and PJI, respectively. The MR analysis demonstrated that body mass index was positively associated with the risk of mechanical complications (odds ratio [OR]: 1.42; p < 0.001). Higher educational attainment was associated with a decreased risk of mechanical complications (OR: 0.55; p < 0.001) and PJI (OR: 0.43; p = 0.001). Type 2 diabetes was suggestively associated with mechanical complications (OR, 1.18, p = 0.02), and hypertension was suggestively associated with PJI (OR, 1.41, p = 0.008). Other lifestyle factors, including smoking and alcohol consumption, were not causally related to postoperative complications. Conclusions : The genetic loci near PPP1R3B and RBM26 influenced the risk of post-TJA mechanical complications and infections, respectively. The effects of genetic and modifiable risk factors, including body mass index and educational attainment, underscore the need to perform personalized preoperative assessments and the postoperative management of surgical patients. These results indicate that integrating genetic screening and lifestyle interventions into patient care can improve the outcomes of TJA and patient quality of life.

Introduction: The biomechanical indication for combining anterolateral structures reconstruction (ASLR) with ACL reconstruction (ACLR) to reduce pivot shift in the knee remains unclear. This study aims to investigate knee functionality after ACL rupture with different combinations of injuries, and to compare the effectiveness of ALSR with ACLR for treating these injuries. Methods: A validated finite element model of a human cadaveric knee was used to simulate pivot shift tests on the joint in different states, including 1) an intact knee; 2) after isolated ACL rupture; 3) after ACL rupture combined with different knee injuries or defect, including a posterior tibial slope (PTS) of 20°, an injury to the anterolateral structures (ALS) and an injury to the posterior meniscotibial ligament of the lateral meniscus (LP); 4) after treating the different injuries using isolated ACLR; v. after treating the different injuries using ACLR with ALSR. The knee kinematics, maximum von Mises stress (Max.S) on the tibial articular cartilage (TC) and force in the ACL graft were compared among the different simulation groups. Results and discussion: Comparing with isolated ACL rupture, combined injury to the ALS caused the largest knee laxity, when a combined PTS of 20° induced the largest Max.S on the TC. The joint stability and Max.S on the TC in the knee with an isolated ACL rupture or a combined rupture of ACL and LP were restored to the intact level after being treated with isolated ACLR. The knee biomechanics after a combined rupture of ACL and ALS were restored to the intact level only when being treated with a combination of ACLR and ALSR using a large graft diameter (6 mm) for ALSR. However, for the knee after ACL rupture combined with a PTS of 20°, the ATT and Max.S on the TC were still greater than the intact knee even after being treated with a combination of ACLR and ALSR. The finite element analysis showed that ACLR should include ALSR when treating ACL ruptures accompanied by ALS rupture. However, pivot shift in knees with a PTS of 20° was not eliminated even after a combined ACLR and ALSR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declare that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Wang, Yao, He, Wang and Cheng.)

Background: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored., Methods: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE -/- mice, while EC-specific knockdown of Nrf2 was generated in Cdh5 Cre Cas9 floxed-stop ApoE -/- mice., Results: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE -/- mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5 Cre Cas9 floxed-stop ApoE -/- mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis., Conclusions: Upon HCD feeding in ApoE -/- mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Study Design: Biomechanical testings and finite element analysis., Objectives: This study aims to investigate how annulus fibrosus (AF) incision size (RIS, Ratio of incision width to AF height) and shape affect intervertebral disc (IVD) biomechanics., Methods: A validated finite element model of lumbar spines simulated various incisions in the middle-right posterior region of the AF, with different sizes and shapes. Simulations included axial compression, flexion, extension, bending, and rotation. Parameters assessed included stability, re-herniation, and IVD degeneration by analyzing stress, height, Intradiscal pressure (IDP), and the range of motion (ROM)., Results: Incision increased AF stress and ROM under 3 Nm moment, with values rising as RIS increased. RIS exceeding 40% resulted in a 20% AF stress increase during compression and extension, while RIS over 50% led to over 20% AF stress increase during other motions. Incision stress also increased with higher RIS, particularly surpassing 50% RIS. IDP rose across all incision shapes. Endplate stress increased (9.9%-48.9%) with larger incisions, with average increases of 12.8%, 12.7%, 30.5%, and 22.8% for circular, oval, square, and rectangular incisions. Compression and rotation minimally affected NP pressure (<15%), while flexion (19.8%-38.8%) and bending (18.5%-43.9%) had a more pronounced effect. ROM increased with RIS (20.0% ∼ 77.4%), especially with an incision RIS exceeding 40%., Conclusions: AF injury elevates AF stress, reduces spine stability, heightens degeneration risk with increasing RIS. Reherniation risk rises when RIS exceeds 40%. Circular or oval incisions maintain spine biomechanics better than square or rectangular ones., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Endothelial dysfunction is the most common pathological feature of cardiovascular diseases, including diabetes mellitus, hypertension and atherosclerosis. It affects both macro- and micro-vasculatures, causing functional impairment of multiple organs. Pien Tze Huang (PZH) is a well-studied traditional Chinese medicine (TCM) with multiple pharmacological properties that produces therapeutic benefits against colorectal cancer, non-alcoholic steatohepatitis and neurodegenerative diseases. However, it is unknown how PZH affects vascular function under pathological conditions. Therefore, this study aimed to investigate the effect of PZH on endothelial function and the underlying mechanisms in db/db diabetic mice. The results showed that chronic treatment of PZH (250 mg/kg/day, 5 weeks) improved endothelial function by restoring endothelium-dependent relaxation through the activation of the Akt-eNOS pathway and inhibition of endothelial oxidative stress, which increased nitric oxide bioavailability. Furthermore, PZH treatment increased insulin sensitivity and suppressed inflammation in diabetic mice. These new findings suggest that PZH may have vaso-protective properties and the potential to protect against diabetic vasculopathy by preserving endothelial function., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As a major risk factor for cardiometabolic diseases, aging refers to a gradual decline in physiological function, characterized with 12 conspicuous hallmarks, like telomere attrition, chronic inflammation, and dysbiosis. Common vascular aging hallmarks include endothelial dysfunction, telomere dysfunction, and vascular inflammation. In this study, we sought to test the hypothesis that young-derived gut microbiota retards vascular aging hallmarks and metabolic impairments in aged hosts. We also aimed to study the therapeutic efficacy of young microbiota in hosts of different ages. Fecal microbiota transplantation (FMT) from young to aged or middle-aged C57BL/6 mice was conducted for 6 consecutive weeks after antibiotic pretreatment. Endothelium-dependent relaxations (EDRs) in mouse arteries were determined by wire myography. Inflammation and AMPK/SIRT1 signaling in mouse aortas and intestines were studied by biochemical assays. The telomere function of aortas and intestines, in terms of telomerase reverse transcriptase expression, telomerase activity, and relative telomere length, were also studied. FMT significantly reverted vascular dysfunction and metabolic impairments in middle-aged mice than in aged mice. Besides, FMT significantly reverted inflammation and telomere dysfunction in aortas and intestines of middle-aged mice. Improved intestinal barrier function and activated AMPK/SIRT1 signaling potentially underlie benefits of FMT. The findings imply gut-vascular connection as potential target against age-associated cardiometabolic disorders, highlight crosstalk among aging hallmarks, and suggest a critical timepoint for efficacy of anti-aging interventions.

A recent resurgence in the incidence of syphilis has sparked a new interest in this old disease. Syphilitic uveitis remains a challenging disease, among the variable syphilis infections, due to the diagnostic complexity and the wide clinical manifestations. Here, we provide recommendations regarding clinical manifestations, diagnosis, and treatment for patients with syphilitic uveitis in Taiwan based on an expert meeting and consensus from experienced uveitis specialists., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Introduction: Kidney cancer is a common urological malignancy worldwide with an increasing incidence in recent years. Among all subtypes, renal cell carcinoma (RCC) represents the most predominant malignancy in kidney. Clinicians faced a major challenge to select the most effective and suitable treatment regime for patients from a wide range of modalities, despite improved understanding and diagnosis of RCC., Objective: Recently, organoid culture gained more interest as the 3D model is shown to be highly patient specific which is hypothetically beneficial to the investigation of precision medicine. Nonetheless, the development and application of organotypic culture in RCC is still immature, therefore, the primary objective of this study was to establish an organoid model for RCC., Materials and Methods: Patients diagnosed with renal tumor and underwent surgical intervention were recruited. RCC specimen was collected and derived into organoids. Derived organoids were validated by histological examminations, sequencing and xenograft. Drug response of organoids were compared with resistance cell line and patients' clinical outcomes., Results: Our results demonstrated that organoids could be successfully derived from renal tumor and they exhibited high concordance in terms of immunoexpressional patterns. Sequencing results also depicted concordant mutations of driver genes in both organoids and parental tumor tissues. Critical and novel growth factors were discovered during the establishment of organoid model. Besides, organoids derived from renal tumor exhibited tumorigenic properties in vivo. In addition, organoids recapitulated patient's in vivo drug resistance and served as a platform to predict responsiveness of other therapeutic agents., Conclusion: Our RCC organoid model recaptiluated histological and genetic features observed in primary tumors. It also served as a potential platform in drug screening for RCC patients, though future studies are necessary before translating the outcomes into clinical practices., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)