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Debbie C Chen,1 Ehrin J Armstrong,2 Gagan D Singh,1 Ezra A Amsterdam,1 John R Laird1 1Department of Internal Medicine, Vascular Center and Division of Cardiovascular Medicine, University of California, Davis, Sacramento, CA, USA; 2Division of Cardiology and VA Eastern Colorado Healthcare System, University of Colorado, Denver, CO, USA Background: Current guidelines recommend aspirin, statins, angiotensin-converting enzyme inhibitors (ACEIs), and smoking abstinence for all patients with vascular disease. There is little data on the variation in adherence to guideline-recommended therapies among patients with different clinical manifestations of vascular disease. Purpose: To analyze the variation in adherence to guideline-recommended therapies among patients with diverse manifestations of vascular disease. Methods: We analyzed a comprehensive database of all patients with critical limb ischemia, claudication, acute limb ischemia, carotid artery stenosis, subclavian artery stenosis, renal artery stenosis, or mesenteric ischemia who underwent angiography between 2006 and 2013 at a multidisciplinary vascular center. Results: Among 1,114 patients with vascular disease, adherence to guideline-recommended therapy at time of angiography included use of aspirin in 936 (84%), statins in 753 (68%), ACEIs in 673 (60%), and smoking abstinence in 788 (71%). A total of 335 (30%) patients utilized all four guideline-recommended therapies. Adherence to four guideline-recommended therapies was lowest among patients with acute limb ischemia (14%) and highest among patients with renal artery stenosis (37%). Among all patients with vascular disease, the range of adherence to individual guidelines was 64%–91% for aspirin, 43%–83% for statins, 49%–66% for ACEIs, and 47%–78% for smoking abstention. Conclusion: The majority of patients with diverse manifestations of vascular disease take aspirin and abstain from smoking while fewer patients are prescribed ACEIs and statins. Among the current recommendations, statins have the widest variation in adherence. Less than one-third of patients with diverse manifestations of vascular disease are prescribed all four guideline-recommended therapies. Keywords: peripheral arterial disease, secondary prevention, statin medications

Martin F Bjurstrom,1,* Andrea L Nicol,2,* Parviz K Amid,3 David C Chen3 1Department of Anesthesiology, UCLA, Los Angeles, CA, USA; 2Department of Anesthesiology, University of Kansas, Kansas City, KS, USA; 3Department of Surgery, Lichtenstein Amid Hernia Clinic at UCLA, UCLA, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Inguinal hernia repair is one of the most common surgeries performed worldwide. With the success of modern hernia repair techniques, recurrence rates have significantly declined, with a lower incidence than the development of chronic postherniorrhaphy inguinal pain (CPIP). The avoidance of CPIP is arguably the most important clinical outcome and has the greatest impact on patient satisfaction, health care utilization, societal cost, and quality of life. The etiology of CPIP is multifactorial, with overlapping neuropathic and nociceptive components contributing to this complex syndrome. Treatment is often challenging, and no definitive treatment algorithm exists. Multidisciplinary management of this complex problem improves outcomes, as treatment must be individualized. Current medical, pharmacologic, interventional, and surgical management strategies are reviewed. Keywords: inguinodynia, chronic postherniorrhaphy inguinal pain, inguinal hernia

Wei-Ting Wu,1 Yu-Hui Huang,2,3 Der-Cherng Chen,4 Yu-Hsuan Huang,1 Li-Wei Chou1,5 1Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, Taiwan; 4Center of Neuropsychiatry, Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan, 5School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, TaiwanAbstract: Transverse myelitis is a rare inflammatory myelopathy characterized by loss of motor and sensory function below the affected level of the spinal cord, and causes neurogenic bowel and bladder. Occasionally, it also causes neuropathic pain with spasticity. Traditional therapies for neuropathic pain are multiple, including multimodal analgesic regimens, antiepileptic or antidepressant medications, opioids, sympathetic blocks, and spinal cord stimulation. Persistent neuropathic pain can cause emotional distress by affecting sleep, work, recreation, and emotional well-being. Here we report the case of a patient suffering from intractable neuropathic pain following acute transverse myelitis that was not relieved by combinations of nonsteroidal anti-inflammatory, antiepileptic, antidepressant, and opioid medications, or by acupuncture. Implantation of an intrathecal morphine pump controlled the pain successfully without side effects, and enabled the patient to embark on intensive rehabilitation. The patient's muscle strength has improved significantly and the patient may soon be able to use a walker with minimal assistance.Keywords: intrathecal morphine pump, neuropathic pain, rehabilitation, transverse myelitis

Adaptive optics (AO) is used for improving lateral resolution in opthalmic Optical-Coherence-Tomography (OCT) to correct for the aberrations in the human eye. AO works by measuring aberrations using a wavefront sensor and applying this information to the control of a deformable mirror in a closed loop, thereby compensating for the measured aberrations. This instrument combines the advantages of FD-OCT and advanced microtechnology for AO, using 35-element bimorph deformable mirror. AO system can effectively compensate low-order aberrations and maintain low rms wavefront error during closed-loop operations.

It is proposed that gut-liver-lung axis plays an important role in the pathophysiologic development of the critical illness, and it induces excessive inflammatory response in vivo and multiple organ dysfunction syndrome. The mechanisms of therapeutic effects of rhubarb on critical patients are studied based on the theory of Chinese traditional medicine. Researches demonstrate that rhubarb can be used to protect gut barrier, maintain intestinal micro-ecological environment and prevent bacterial translocation. It also can be used to inhibit the release of inflammatory mediators by liver inflammatory-effector cells, reduce inflammatory reaction in the liver and protect hepatic cell functions. Furthermore, rhubarb can be used to reduce pulmonary vascular permeability and extenuate pulmonary edema, inhibit the release of neutrophil myeloperoxidase, and lower the level of inflammatory response and decrease inflammatory mediators in circulation. The above results indicate that rhubarb may interrupt or partly interrupt the gut-liver-lung axis after trauma and reduce the intensity of systemic inflammatory response syndrome. Therefore, rhubarb may obviously lower the incidence of multiple organ dysfunction syndrome and be used to prevent and treat systemic inflammatory response syndrome and multiple organ dysfunction syndrome after trauma. [ABSTRACT FROM AUTHOR]

Background: Whole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot-Marie-Tooth disease.Methods: We identified a family with a recessive form of Charcot-Marie-Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members.Results: We identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot-Marie-Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome.Conclusions: As shown in this study of a family with Charcot-Marie-Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients. [ABSTRACT FROM AUTHOR]

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has become an increasingly established imaging modality in the staging of prostate cancer (PCa). Numerous PSMA-based tracers are currently available, however, there is a lack of consensus on the optimal radiotracer(s) for PSMA PET/CT. This study aims to investigate whether Fluorine-18 ( 18 F)-labelled PSMA PET/CT is significantly different from Gallium-68 ( 68 Ga) in primary diagnosis and/or secondary staging of prostate cancer following biochemical recurrence., Methods: A critical review of MEDLINE, EMBASE, PubMed and Web of Science databases was performed in May 2023 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies that directly compared 18 F-based PSMA radiotracers and [ 68 Ga]Ga-PSMA-11 in terms of the normal organ SUV or the lesion SUV or the detection rate were assessed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2)., Results: Twenty-four studies were analysed. [ 18 F]DCFPyL and [ 18 F]PSMA-1007 were the two most commonly studied 18 F based PSMA tracers. [ 18 F]JK-PSMA-7, [ 18 F]rhPSMA-7, [ 18 F]AlF-PSMA-11 were the new tracers evaluated in a limited number of studies. Overall, [ 18 F]DCFPyL was observed to have a similar lesion detection rate to [ 68 Ga]Ga-PSMA-11 with no increase in false positive rates. [ 18 F]PSMA-1007 was found to have a greater local lesion detection rate because of its predominant hepatobiliary excretory route. However, [ 68 Ga]Ga-PSMA-11 was observed to have a similar local lesion detection rate in studies that administer patients with furosemide prior to the scan. In addition, [ 18 F]PSMA-1007 was found to have a significant number of benign bone uptakes., Conclusions: [ 18 F]DCFPyL was observed to be similar to [ 68 Ga]Ga-PSMA-11. [ 18 F]PSMA-1007 was observed to be less preferrable to [ 68 Ga]Ga-PSMA-11 due to its high benign bone uptakes. Overall, there was not enough evidence in differentiating the radiotracers based on their clinical impacts., (© 2023. The Author(s).)

Objective: This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection., Methods: From March 1, 2020 to July 31, 2021, 80 patients were enrolled, including 40 undergoing intraperitoneal Pringle maneuver (IPM) and 40 extraperitoneal Pringle maneuver (EPM). The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices., Results: There were no significant differences in the basic characteristics or types of hepatectomy, intraoperative blood loss, intraoperative blood transfusion, or hepatectomy time between the IPM and EPM groups. However, the blocking and operation time in the IPM group was shorter than that in the EPM group. There were no significant differences in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels on the first day after surgery or in total bilirubin (TBIL) or albumin (ALB) levels on the first, third, or fifth days after surgery. However, C-reactive protein (CRP) levels on the first and third days, ALT and AST levels on the third and fifth days were lower, and hospital stay after surgery was shorter in the IPM group than in the EPM group., Conclusion: IPM using bulldog clamps is simple, safe, and effective. The inflammatory reaction is less severe, the degree of liver function injury is lower, and recovery is faster., Competing Interests: Conflict of Interest Statement. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024. Huazhong University of Science and Technology.)

Background: Radiotherapy peer review is recognized as a key component of institutional quality assurance, though the impact is ill-defined. We conducted the first systematic review and meta-analysis to date to quantify the impact of institutional peer review on the treatment planning workflow including radiotherapy contours, prescription and dosimetry., Methods: We searched several medical and healthcare databases from January 1, 2000, to May 25, 2024, for papers that report on the impact of institutional radiotherapy peer review on treatment plans. We conducted random-effects meta-analyses of proportions to summarize the rates of any change recommendation and major change recommendation (suggesting re-planning or re-simulation due to safety concerns) following peer review processes. To explore differences in change recommendations dependent on location, radiotherapy intent, technique, and peer review structure characteristics, we conducted analyses of variance., Results: Of 9,487 citations, we identified 55 studies that report on 96,444 case audits in 10 countries across various disease sites. The pooled proportion of any change recommendation was 28 % (95 %CI = 21-35) and major change recommendation was 12 % (95 %CI = 7-18). Proportions of change recommendation were not impacted by any treatment characteristics. The most common reasons for change recommendation include target volume delineation (25/55; 45 %), target dose prescription (18/55; 33 %), organ at risk dose prescription (5/55; 9 %), and organ at risk volume delineation (3/55; 5 %)., Conclusions: Our review provides evidence that peer review results in treatment plan change recommendations in over one in four patients. The results suggest that some form of real-time, early peer review may be beneficial for all cases, irrespective of treatment intent or RT technique., 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. Published by Elsevier B.V.)

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes possess therapeutic potential against degenerative diseases. This study aimed to investigate the effects of BMSC-derived exosomes on intervertebral disc degeneration (IVDD) and explore the underlying molecular mechanisms. Through transcriptome sequencing and histological analysis, we observed a significant increase in HIF-1α expression in degenerative nucleus pulposus (NP) tissues. The addition of HIF-1α resulted in elevated expression of inflammatory factors IL-1β and IL-6, higher levels of matrix-degrading enzyme MMP13, and lower expression of aggrecan in NP cells. Co-culturing with BMSCs diminished the expression of HIF-1α, MMP13, IL-1β, and IL-6 in degenerative NP cells induced by overload pressure. miRNA chip analysis and PCR validation revealed that miR-145a-5p was the primary miRNA carried by BMSC-derived exosomes. Overexpression of miR-145a-5p was effective in minimizing the expression of HIF-1α, MMP13, IL-1β, and IL-6 in degenerative NP cells. Luciferase reporter assays confirmed USP31 as the target gene of miR-145a-5p, and the regulation of NP cells by BMSC-derived exosomes via miR-145a-5p was dependent on USP31. In conclusion, BMSC-derived exosomes alleviated IVDD through the miR-145a-5p/USP31/HIF-1α signaling pathway, providing valuable insights into the treatment of IVDD., Competing Interests: Declarations Ethical Approval The nucleus pulposus specimens were collected with the approval of the Ethics Committee of the First Affiliated Hospital of the Air Force Medical University of the People’s Liberation Army (Approval number: KY20222063-D-2) and written informed consent was obtained from the specimen donors or their families. All experimental processes were performed with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, eighth edition, 2011), and approved by the Ethics Committee of the First Affiliated Hospital of the Air Force Medical University of the People’s Liberation Army (Approval number: KY20222063-D-2). Consent for Publication The authors affirm that all participants provided informed consent for publication of the paper. Consent to Participate Informed consent was obtained from all individual participants included in the study. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In the field of orthopedic surgery, tourniquets are often used to achieve a clear operative field, expedite operations, and minimize hemorrhagic events. However, determining the optimal tourniquet inflation pressure is a topic of debate. The current approach involves using a constant tourniquet pressure, although this is associated with the potential to augment the risk of tourniquet-associated complications. The Association of Surgical Technologists recommends a tourniquet pressure of systolic blood pressure plus 50 mm Hg for the upper limb and 100 mm Hg for the lower limb. Nevertheless, this method lacks robust support from high-quality medical literature. Therefore, the study aimed to compare the hemostatic efficacy and disparities in tourniquet pressure settings based on systolic blood pressure versus those using the constant-pressure method. The findings might outline the theoretical framework necessary for advocating for tourniquet pressure setups guided by systolic blood pressure., Methods/design: This randomized controlled study classified the tourniquet pressure regimen into two groups: one based on the patient's systolic blood pressure (the study group) and the other using a constant pressure (the control group). The study included patients aged between 16 and 70 who presented with fresh fractures (less than 3 weeks) of the lower and upper limbs. All the included patients required surgical treatment involving the intraoperative use of a tourniquet and had no contraindications to this surgery. Our primary outcome was to assess the surgeon's satisfaction with the hemostasis achieved in the operative field. We also examined the changes in the circumference of the limb where the tourniquet was applied and tracked any postoperative complications and their incidence. The study ultimately encompassed 144 patients., Discussion: Despite the prevalent use of tourniquets in surgical operations related to limb fractures, conflicting viewpoints persist concerning the adjustments in pressure and other elements. The study aimed to compare the hemostatic efficacy and disparities in tourniquet pressure settings based on systolic blood pressure versus those using the constant-pressure method., Study Registration: The study was duly recorded in the Chinese Clinical Trial Registry on May 13, 2022 (Registration number: ChiCTR2200059867)., Registration Website: https://www.chictr.org.cn/showproj.aspx?proj=162504., Competing Interests: 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., (© 2024 Published by Elsevier Inc.)

Piezocatalysis is considered to be a favorable catalytic technology by utilizing external mechanical stimulation to promote the specific redox reactions. The application of piezocatalysis in batteries is promising but faces formidable challenges. Herein, the operation principles of piezocatalysis were successfully demonstrated by constructing solid-state Li-Se and Li-S battery models with interfacial stress accumulation. Lead zirconate titanate with an ultra-high piezoelectric coefficient was applied as the piezoelectric catalyst. The uniformity of the dipole orientation in materials was essential for achieving piezocatalysis in batteries. The accumulated high-stress converts to piezopotential for catalyzing most reaction processes in batteries, while the rapid stress change prevents the internal charge reorganization, ensuring continuous efficient catalysis. The internal stress change alters the internal polarisation strength, driving excess screening charge to participate in the electrochemical reaction. Under piezocatalysis, solid-state Li-Se batteries exhibited a initial discharge capacity of 670.9 mAh g -1 (99.4 % of the theoretical value) at 0.1 C, and Li-S batteries showed a capacity of 1463 mAh g -1 at 0.2 C, which was still maintained up to 1084 mAh g -1 at an elevated rate of 0.5 C. This piezocatalysis strategy provides a strong theoretical basis and design specification for enhancing Li-Se and Li-S battery reaction kinetics., (© 2024 Wiley-VCH GmbH.)

Artificial sweeteners are generally used and recommended to alternate added sugar for health promotion. However, the health effects of artificial sweeteners remain unclear. In this study, we included 6371 participants from the National Health and Nutrition Examination Survey with artificial sweetener intake records. Logistic regression and Cox regression were applied to explore the associations between artificial sweeteners and risks of cardiometabolic disorders and mortality. Mendelian randomisation was performed to verify the causal associations. We observed that participants with higher consumption of artificial sweeteners were more likely to be female and older and have above medium socio-economic status. After multivariable adjustment, frequent consumers presented the OR (95 % CI) for hypertension (1·52 (1·29, 1·80)), hypercholesterolaemia (1·28 (1·10, 1·50)), diabetes (3·74 (3·06, 4·57)), obesity (1·52 (1·29, 1·80)), congestive heart failure (1·89 (1·35, 2·62)) and heart attack (1·51 (1·10, 2·04)). Mendelian randomisation confirmed the increased risks of hypertension and type 2 diabetes. Moreover, an increased risk of diabetic mortality was identified in participants who had artificial sweeteners ≥ 1 daily (HR = 2·62 (1·46, 4·69), P = 0·001). Higher consumption of artificial sweeteners is associated with increased risks of cardiometabolic disorders and diabetic mortality. These results suggest that using artificial sweeteners as sugar substitutes may not be beneficial.

Objective: To examine the role of bowel diversion and reconstructive surgeries in managing Fournier's gangrene (FG) to facilitate multidisciplinary collaboration between urologists, colorectal and plastic surgery teams., Methods: A review of the literature was conducted using the databases Medline, Embase, PubMed in June 2023. The review included studies that evaluated the outcomes of FG following reconstructive surgeries or diverting colostomies., Results: The existing evidence suggests that bowel diversion and colostomy formation could reduce the need for further debridement, shorten the time to wound healing, and facilitate skin graft or flap uptake in patients with FG. Additionally, the psychological impact of a stoma was shown not to be a major concern for patients. However, stoma carries a risk of perioperative complications and therefore may prolong the length of hospital stay. In reviewing the evidence for reconstruction in FG, large and deep defects seem to benefit from skin grafts or flaps. Noticeably, burial of testicles in thigh pockets has grown out of favour due to concerns regarding the thermoregulation of the testicles and the psychological impact on patients., Conclusion: The use of bowel diversion and reconstructive surgeries in managing FG is case dependent. Therefore, it is important to have close discussions with colorectal and plastic surgery teams when managing FG., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

To develop new types of dynamic molecular devices with atomic-scale control over electronic function, new types of molecular switches are needed with time-dependent switching probabilities. We report such a molecular switch based on proton-coupled electron transfer (PCET) reaction with giant hysteric negative differential resistance (NDR) with peak-to-valley ratios of 120 ± 6.6 and memory on/off ratios of (2.4 ± 0.6) × 10 3 . The switching dynamics probabilities are modulated by bias voltage sweep rate and can also be controlled by pH and relative humidity, confirmed by kinetic isotope effect measurements. The demonstrated dynamical and environment-specific modulation of giant NDR and memory effects provide new opportunities for bioelectronics and artificial neural networks., (© 2024. The Author(s).)

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with β-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.

Cardiomyopathies, encompassing hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), constitute a diverse spectrum of heart muscle diseases that often culminating in heart failure (HF). The inherent molecular heterogeneity of these conditions has implications for prognosis and therapeutic strategies. Publicly available microarray and RNA sequencing (RNA-seq) data sets of HCM (n = 106 from GSE36961) and DCM (n = 18 from GSE135055 and 166 from GSE141910) patients were employed for our analysis. The Non-negative Matrix Factorization (NMF) algorithm was applied to explore the molecular stratification within HCM and DCM, and enrichment analysis was performed to delineate their biological characteristics. By integrating bulk and single-nucleus RNA-seq (snRNA-seq) data, we identified a potential biomarker for HCM progression and cardiac fibrosis, which was subsequently validated using mendelian randomization and in vitro. Our application of NMF identified two distinct molecular clusters. Particularly, a profibrotic, heart failure with reduced ejection fraction (HFrEF)-resembling Cluster 1 emerged, characterized by diminished expression of CORIN and a high degree of fibroblast activation. This cluster also exhibited lower left ventricular ejection fraction (LVEF) and worse prognostic outcomes, establishing the significance of this molecular subclassification. We further found that overexpression of CORIN could mitigate TGFβ1-induced expression of col1a1 and α-SMA in neonatal rat cardiac fibroblasts. Our results indicated the heterogeneity of HCM population, and further evidenced the participation of corin in the progression of HCM, DCM and HFrEF. Nevertheless, our study is constrained by the lack of corresponding clinical data and experimental validation of the identified subtypes. Therefore, further studies are warranted to elucidate the downstream pathways of corin and to validate these findings in independent patient cohorts., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: Post-operative prescription opioid use is a known risk factor for persistent opioid use. Despite the increased utilization of robotic-assisted surgery (RAS) for inguinal hernia repair (IHR), little is known whether this minimally invasive approach results in less opioid consumption. In this study, we compare long-term opioid use between RAS versus laparoscopic (Lap) versus open surgery for IHR., Methods: A retrospective cohort study of opioid-naïve patients who underwent outpatient primary IHR was conducted using the Merative™ MarketScan® (Previously IBM MarketScan®) Databases between 2016 and 2020. Patients not continuously enrolled 180 days before/after surgery, who had malignancy, pre-existing chronic pain, opioid dependency, or invalid prescription fill information were excluded. Among patients exposed to opioids peri-operatively, we assessed long-term opioid use as any opioid prescription fill within 90 to 180 days post-surgery. Secondary outcomes were controlled substance schedule II/III opioid fill, and high-dose opioid fill defined as > 50 morphine milligram equivalent per day. An Inverse-probability of treatment weighted logistic regression was used to compare outcomes between groups with p-value of < 0.05 considered statistically significant., Results: A total of 41,271 patients were identified (2070 (5.0%) RAS, 16,704 (40.5%) Lap, and 22,497 (54.5%) open surgery). RAS was associated with less likelihood of prescription fills for any opioid (OR 0.78, 95% CI 0.60 to 0.98 versus Lap; OR 0.67, 95% CI 0.52 to 0.85 versus open), and schedule II/III opioid (OR 0.74, 95% CI 0.56 to 0.96 versus Lap; OR 0.68, 95% CI 0.51 to 0.88 versus open), but comparable high-dose opioid fill (OR 0.95, 95% CI 0.54 to 1.55 versus Lap; OR 0.96, 95% CI 0.56 to 1.52 versus open). Lap and open surgery had no significant difference., Conclusion: In this cohort of patients derived from a national commercial claims dataset, patients undergoing RAS had a decreased risk of long-term opioid use compared to laparoscopic and open surgery patients undergoing IHR., (© 2024. The Author(s).)

Osteoarthritis (OA) is a degenerative disease commonly seen in middle-aged and elderly people. Multiple cytokines are involved in the local tissue damage in OA. Currently, non-pharmacologic and surgical interventions are the main conventional approaches for the treatment of OA. In terms of pharmaceutical drug therapy, NSAIDs and acetaminophen are mainly used to treat OA. However, it is prone to various adverse reactions such as digestive tract ulcer, thromboembolism, prosthesis loosening, nerve injury and so on. With the in-depth study of OA, more and more novel topical drug delivery strategies and vehicles have been developed, which can make up for the shortcomings of traditional dosage forms, improve the bioavailability of drugs, and significantly reduce drug side effects. This review summarizes the immunopathogenesis, treatment guidelines, and progress and challenges of topical delivery technologies of OA, with some perspectives on the future pharmacological treatment of OA proposed., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Shentu et al.)

Objective: To analyze the clinical characteristics of patients with Epstein-Barr virus(EBV)-associated hemophagocytic lymphohistiocytosis(HLH) with acute kidney injury(AKI)., Methods: EBV-HLH patients who were hospitalized in our hospital from January 2014 to December 2020 were collected, and their clinical characteristics, treatment, concurrent acute kidney injury and prognosis were retrospectively analyzed., Results: In this study, the incidence of AKI complicated by EBV-HLH was 65.5%, and the 28-day mortality rate was 15.3%. Compared with non-AKI group, patients in the AKI group had higher levels of bilirubin, lactate dehydrogenase, creatinine, urea nitrogen, and β 2 -microglobulin（β 2 -MG）, poorer coagulation, and lower soluble IL-2 receptor （sCD25）. Patients in the AKI group had a higher proportion of chemotherapy, transplantation, mechanical ventilation, and the application of vasoactive medications, and were hospitalized for longer periods of time, with higher in-hospital mortality rates and 28-day mortality rates. Patients in the AKI group were analyzed in subgroups according to the Kidney Disease Improving Global Outcomes （KDIGO）classification, and the levels of leukocytes, bilirubin, albumin, creatinine, urea nitrogen, β 2 -MG, activated partial thromboplastin time （APTT）, and prothrombin time activity （PTA）were more responsive to the severity of the patient's condition. KDIGO grade 2 and 3 had higher proportions of receiving transplants, diuretics, organ support (mechanical ventilation, application of vasoactive medications, and renal replacement therapy), and admissions to the intensive care unit （ICU）, and with higher in-hospital mortality rates and 28-day mortality rates. Regression analysis found that creatinine, β 2 -MG, APTT, transplantation, and chemotherapy were independent risk factors for the development of AKI; the application of vasoactive drugs was both an independent risk factor for the development of AKI and for death at 28 days; and chemotherapy, length of hospitalization, and HGB and fibrinogen levels were protective factors for death at 28 days., Conclusion: AKI in EBV-HLH has high incidence and high rate of progression to severe disease and death, early attention should be given and strengthened in order to carry out early treatment and improve the prognosis of patients.

Background: Prevention measures for palliative care and the provision of discharge planning services for inpatients in Taiwan before and during the COVID-19 pandemic had not been investigated. This study was aimed to investigate the factors associated with heightened palliative care needs and increased mortality rates., Methods: This research adopts a retrospective case-control study design. The investigation encompasses patients admitted before the pandemic (from January 1, 2019, to May 31, 2019) and during the COVID-19 pandemic (from January 1, 2020, to May 31, 2020). The case group consisted of 231 end-of-life inpatients during the pandemic, control group was composed of the pool of inpatients with pre-pandemic and matched with cases by sex and age in a 1:1 ratio., Results: The results showed that the prevalence of respiratory failure symptoms ( p  = 0.004), residing in long-term care facilities ( p  = 0.017), palliative care needs assessment scores ( p  = 0.010), as well as the provision of guidance for nasogastric tube feeding ( p  = 0.002), steam inhalation ( p  = 0.003), turning and positioning ( p  < 0.001), percussion ( p  < 0.001), passive range of motion ( p  < 0.001), and blood pressure measurement ( p  < 0.001). Furthermore, the assessment of the necessity for assistive devices, including hospital beds, also exhibited statistically significant variations ( p  < 0.001). Further investigation of the factors associated with high palliative care needs and the risk of mortality for both the case and control groups. Risk factors for high palliative care needs encompassed assessments of daily activities of living, the presence of pressure ulcers, and the receipt of guidance for ambulation. Risk factors for mortality encompassed age, a diagnosis of cancer, palliative care needs assessment scores, and the provision of guidance for disease awareness., Conclusion: This research highlights the heightened risk of COVID-19 infection among end-of-life inpatients during the COVID-19 pandemic. The findings of this study may advance care planning to alleviate avoidable suffering. To meet the needs of inpatients during pandemic, healthcare professionals should undergo comprehensive palliative care training and receive policy support., 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 Wu, Hsiaog, Huang, Chu and Liu.)

Gastric cancer poses diverse treatment challenges due to its high tumor heterogeneity. Through the use of patient-derived tumor organoid (PDO) models, new research 1 has identified genes and molecular signatures that are predictive of chemotherapeutic response, providing valuable insights for clinical management and translational advancements., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Parosteal osteosarcomas are uncommon malignant bone tumors that arise from the bone surface. Their heterogenous components can present challenges in diagnosis. We present a case of a rare variant of this tumor known as an osteochondroma-like parosteal osteosarcoma, which was initially misdiagnosed as a cartilaginous tumor on core needle biopsy. Surgical resection of the tumor ultimately allowed for definitive diagnosis. Our case demonstrates the limitations of needle biopsy in diagnosing variants of parosteal osteosarcoma and the vital role of multidisciplinary discussions in guiding diagnosis and treatment. Furthermore, our case utilizes 3-dimensional printing technology in the surgical treatment, and illustrates the recent advances in patient-specific surgical techniques., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Head and Neck Squamous Cell Carcinoma (HNSCC) remains a significant health burden due to tumor heterogeneity and treatment resistance, emphasizing the need for improved biological understanding and tailored therapies. This study enrolled 31 HNSCC patients for the establishment of patient-derived tumor organoids (PDOs), which faithfully maintained genomic features and histopathological traits of primary tumors. Long-term culture preserved key characteristics, affirming PDOs as robust representative models. PDOs demonstrated predictive capability for cisplatin treatment responses, correlating ex vivo drug sensitivity with patient outcomes. Bulk and single-cell RNA sequencing unveiled molecular subtypes and intratumor heterogeneity (ITH) in PDOs, paralleling patient tumors. Notably, a hybrid epithelial-mesenchymal transition (hEMT)-like ITH program is associated with cisplatin resistance and poor patient survival. Functional analyses identified amphiregulin (AREG) as a potential regulator of the hybrid epithelial/mesenchymal state. Moreover, AREG contributes to cisplatin resistance via EGFR pathway activation, corroborated by clinical samples. In summary, HNSCC PDOs serve as reliable and versatile models, offer predictive insights into ITH programs and treatment responses, and uncover potential therapeutic targets for personalized medicine., Competing Interests: Competing interests The authors declare no potential conflicts of interest.

Upper aerodigestive squamous cell carcinoma (UASCC) is a common and aggressive malignancy with few effective therapeutic options. Here, we investigate amino acid metabolism in this cancer, surprisingly noting that UASCC exhibits the highest methionine level across all human cancers, driven by its transporter LAT1. We show that LAT1 is also expressed at the highest level in UASCC, transcriptionally activated by UASCC-specific promoter and enhancers, which are directly coregulated by SCC master regulators TP63/KLF5/SREBF1. Unexpectedly, unbiased bioinformatic screen identifies EZH2 as the most significant target downstream of the LAT1-methionine pathway, directly linking methionine metabolism to epigenomic reprogramming. Importantly, this cascade is indispensable for the survival and proliferation of UASCC patient-derived tumor organoids. In addition, LAT1 expression is closely associated with cellular sensitivity to inhibition of the LAT1-methionine-EZH2 axis. Notably, this unique LAT1-methionine-EZH2 cascade can be targeted effectively by either pharmacological approaches or dietary intervention in vivo. In summary, this work maps a unique mechanistic cross talk between epigenomic reprogramming with methionine metabolism, establishes its biological significance in the biology of UASCC, and identifies a unique tumor-specific vulnerability which can be exploited both pharmacologically and dietarily., Competing Interests: Competing interests statement:The authors declare no competing interest.

Rechargeable aqueous Zn-ion batteries have been deemed a promising energy storage device. However, the dendrite growth and side reactions have hindered their practical application. Herein, inspired by the ultrafluidic and K + ion-sieving flux through enzyme-gated potassium channels (KcsA) in biological plasma membranes, a metal-organic-framework (MOF-5) grafted with -ClO 4 groups (MOF-ClO 4 ) as functional enzymes is fabricated to mimic the ultrafluidic lipid-bilayer structure for gating Zn 2+ 'on' and anions 'off' states. The MOF-ClO 4 achieved perfect Zn 2+ /SO 4 2- selectivity (∼10), enhanced Zn 2+ transfer number ([Formula: see text]) and the ultrafluidic Zn 2+ flux (1.9 × 10 -3 vs. 1.67 mmol m -2 s -1 for KcsA). The symmetric cells based on MOF-ClO 4 achieve a lifespan of over 5400 h at 10 mA cm -2 /20 mAh cm -2 . Specifically, the performance of the PMCl-Zn//V 2 O 5 pouch cell keeps 81% capacity after 2000 cycles at 1 A g -1 . The regulated ion transport, by learning from a biological plasma membrane, opens a new avenue towards ultralong lifespan aqueous batteries., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Background: Transversus abdominis release (TAR) is an effective technique for treating large midline and off-midline hernias. Recent studies have demonstrated that robotic TAR (rTAR) is technically feasible and associated with improved outcomes compared to open surgery. There is no published experience to date describing abdominal wall reconstruction using the novel robotic platform HUGO RAS System (Medtronic®)., Methods: All consecutive patients who underwent a rTAR in our institution were included. Three of the four arm carts of the HUGO RAS System were used at any given time. Each arm configuration was defined by our team in conjunction with Medtronic® personnel. rTAR was performed as previously described. Upon completion of the TAR on one side, a redocking process with different, mirrored arms angles was performed to continue with the contralateral TAR. Operative variables and early morbidity were recorded., Results: Ten patients were included in this study. The median BMI was 31 (21-40.6) kg/m 2 . The median height was 1.6 m (1.5-1.89 m). A trend of decreased operative time, console time, and redocking time was seen in these consecutive cases. No intraoperative events nor postoperative morbidity was reported. The median length of stay was 3 (1-6) days., Conclusion: Robotic TAR utilizing the HUGO RAS system is a feasible and safe procedure. The adoption of this procedure on this novel platform for the treatment of complex abdominal wall hernias has been successful for our team., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The ancient Chinese medical book "Compendium of Materia Medica" records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1β, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.

Background: Cyclic nucleotides are critical mediators of cellular signalling in glioblastoma. However, the clinical relevance and mechanisms of regulating cyclic nucleotides in glioblastoma progression and recurrence have yet to be thoroughly explored., Methods: In silico, mRNA, and protein level analyses identified the primary regulator of cyclic nucleotides in recurrent human glioblastoma. Lentiviral and pharmacological manipulations examined the functional impact of cyclic nucleotide signalling in human glioma cell lines and primary glioblastoma cells. An orthotopic xenograft mice model coupled with aspirin hydrogels verified the in vivo outcome of targeting cyclic nucleotide signalling., Results: Elevated intracellular levels of cGMP, instead of cAMP, due to a lower substrate efflux from ATP-binding cassette sub-family C member 4 (ABCC4) is engaged in the recurrence of glioblastoma. ABCC4 gene expression is negatively associated with recurrence and overall survival outcomes in glioblastoma specimens. ABCC4 loss-of-function activates cGMP-PKG signalling, promoting malignancy in glioblastoma cells and xenografts. Hydrogels loaded with aspirin, inhibiting glioblastoma progression partly by upregulating ABCC4 expressions, augment the efficacy of standard-of-care therapies in orthotopic glioblastoma xenografts., Conclusion: ABCC4, repressing the cGMP-PKG signalling pathway, is a tumour suppressor in glioblastoma progression and recurrence. Aspirin hydrogels impede glioblastoma progression through ABCC4 restoration and constitute a viable translational approach., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Master transcription factors such as TP63 establish super-enhancers (SEs) to drive core transcriptional networks in cancer cells, yet the spatiotemporal regulation of SEs within the nucleus remains unknown. The nuclear pore complex (NPC) may tether SEs to the nuclear pore where RNA export rates are maximal. Here, we report that NUP153, a component of the NPC, anchors SEs to the NPC and enhances TP63 expression by maximizing mRNA export. This anchoring is mediated through protein-protein interaction between the intrinsically disordered regions (IDRs) of NUP153 and the coactivator BRD4. Silencing of NUP153 excludes SEs from the nuclear periphery, decreases TP63 expression, impairs cellular growth, and induces epidermal differentiation of squamous cell carcinoma. Overall, this work reveals the critical roles of NUP153 IDRs in the regulation of SE localization, thus providing insights into a new layer of gene regulation at the epigenomic and spatial level., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aqueous electrolytes with a low voltage window (1.23 V) and prone side reactions, such as hydrogen evolution reaction and cathode dissolution, compromise the advantages of high safety and low cost of aqueous metal-ion batteries. Herein, introducing catechol (CAT) into the aqueous electrolyte, an outer sphere electron transfer mechanism is initiated to inhibit the water reactivity, achieving an electrochemical window of 3.24 V. In a typical Zn-ion battery, the outer sphere electrons jump from CAT to Zn 2+ -H 2 O at a geometrically favorable situation and between the solvation molecules without breaking or forming chemical bonds as that of the inner sphere electron transfers. The excited state π-π stacking further leads to the outer sphere electron transfer occurring at the electrolyte/electrode interface. This high-voltage electrolyte allows achieving an operating voltage two times higher than that of the usual aqueous electrolytes and provides almost the highest energy density and power density for the V 2 O 5 -based aqueous Zn-ion full batteries. The Zn//Zn symmetric battery delivers a 4000 h lifespan, and the Zn//V 2 O 5 full battery achieves a ∼380 W h kg -1 energy density and a 92% capacity retention after 3000 cycles at 1 A g -1 and a 2.4 V output voltage. This outer sphere electron transfer strategy paves the way for designing high-voltage aqueous electrolytes.

This research investigates the control of thickness and weight in plastic extrusion vacuum-thermoforming products to identify optimal key parameters for cost reduction and energy savings. The initial step involves identifying crucial influencing factors. In this step, the Delphi technique was employed through a questionnaire administered to a panel of expert scholars to ensure minimal error and maximal reliability in determining key influencing factors. Consensus was sought to establish appropriateness and consistency. Subsequently, the Taguchi method was applied for quality design and planning of the extrusion vacuum-forming process. The experimental design parameters were selected using an L 18 (2 1 × 3 7 ) orthogonal array, and the desired quality characteristics were determined. Comparative analysis of quantitative production data from two consecutive experiments was conducted, and based on F-values and contribution analysis, the combination of control factors maximizing the Signal-to-Noise (S/N) ratio was identified. The objective is to seek optimal parameters for improving the quality of the plastic polypropylene (PP cup lid) manufacturing process, reducing process variability, and identifying the most robust production conditions. Through multiple actual production prediction experiments, it was determined that five control factors, "polypropylene new material ratio," "T-die lips adjustment thickness", "mirror wheel temperature stability", "molding vacuum pressure time", and "forming mold area design", contribute to the maximization of the S/N ratio, i.e., minimizing variability. Statistical validation confirms a significant improvement in product quality and weight control. Noteworthily, the quality control model and experimental design parameters established in this study are also applicable to other plastic products and bio-based materials, such as PET, HIPS, and biodegradable PLA lids with added calcium carbonate. The results of the experimental production demonstrate its ability to consistently control product weight within the range of 3.4 ± 0.1 g, approaching the specified tolerance limits. This capability results in approximately 2.6% cost savings in product weight, contributing significantly to achieving a company's KPI goals for environmental conservation, energy efficiency, and operational cost reduction. Therefore, the findings of this study represent a substantial and tangible contribution.

Prone positioning ventilation (PPV) is considered one of the essential therapeutic approaches in the management of acute respiratory distress syndrome (ARDS). Several randomized controlled clinical trials have demonstrated the efficacy of PPV in the treatment of patients with ARDS. However, it is not clear whether PPV treatment can reduce mortality in patients with veno-venous extracorporeal membrane oxygenation (VV-ECMO)-supported ARDS and corona virus disease 2019 (COVID-19)-associated ARDS. This review aims to discuss the known and unknown aspects of the mechanism of PPV for ARDS, the clinical efficacy of PPV for ARDS, VV-ECMO-supported ARDS, and COVID-19-related ARDS.

Rationale & Objective: Cystatin C-based estimated glomerular filtration rate (eGFR cys ) has stronger associations with adverse clinical outcomes than creatinine-based eGFR (eGFR cr ). Obesity may be associated with higher cystatin C levels, independent of kidney function, but it is unknown whether obesity modifies associations of eGFR cys with kidney and cardiovascular outcomes., Study Design: Cohort study., Setting & Participants: 27,249 US adults in the Reasons for Geographic and Racial Differences in Stroke Study., Predictors: eGFR cys , eGFR cr , waist circumference, and body mass index (BMI)., Outcome: All-cause mortality, kidney failure, incident atherosclerotic cardiovascular disease (ASCVD), and incident heart failure (HF)., Analytical Approach: Multivariable Cox and Fine-Gray models with multiplicative interaction terms were constructed to investigate whether waist circumference quartiles or BMI categories modified associations of eGFR cys with risks of 4 clinical outcomes., Results: Participants had a mean age of 65 years; 54% were women, 41% were Black, and 21% had an eGFR cys <60mL/min/1.73m 2 . The baseline prevalence of abdominal obesity (waist circumference≥88cm for women or≥102cm for men) was 48% and obesity was 38%. In multivariable adjusted analyses, each 15mL/min/1.73m 2 lower eGFR cys was associated with higher HR and 95% CI of mortality in each waist circumference quartile (first quartile, 1.19 [1.15-1.24]; second quartile, 1.22 [1.18-1.26]; third quartile, 1.20 [1.16-1.24]; fourth quartile, 1.19 [1.15-1.23]) as well as within each BMI category (BMI<24.9: 1.21 [1.17-1.25]; BMI 25.0-29.9: 1.21 [1.18-1.25]; BMI 30.0-34.9: 1.20 [1.16-1.25]; BMI≥35: 1.17, [1.12-1.22]). Neither waist circumference nor BMI modified the association of eGFR cys with mortality, kidney failure, incident ASCVD, or incident HF (all P interaction >0.05)., Limitations: Included only Black and White persons in the United States., Conclusion: Obesity did not modify the association of eGFR cys with all-cause mortality, kidney failure, incident ASCVD, or incident HF. Among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes., Plain-Language Summary: Cystatin C is increasingly used in clinical practice to estimate kidney function, and cystatin C-based eGFR (eGFR cys ) may be used to determine risk for adverse clinical outcomes. Adiposity may increase serum levels of cystatin C, independent of kidney function. This cohort study investigated whether associations of eGFR cys with adverse kidney and cardiovascular outcomes are modified by measures of obesity, waist circumference, and body mass index. We found that obesity does not modify associations of eGFR cys with 4 clinical outcomes and conclude that among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes., (Published by Elsevier Inc.)

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. We used the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess clinical symptoms and cognition. Our results show that the COX2 rs5275 polymorphism was significantly correlated with SCZ and positive symptoms. After 12-week treatment, celecoxib significantly improved the PANSS total and three subscale scores of SCZ patients. Furthermore, patients with the rs5275 TT genotype had greater improvement in PANSS total score than patients carrying the C allele. However, no significant difference in RBANS total and subscale scores existed between the celecoxib and placebo groups at week 12. Our findings suggest that COX2 inhibitors may be promising therapeutics for clinical symptoms rather than cognitive impairment in first episode SCZ patients. COX2 rs5275 gene polymorphism may be implicated in the development and the efficacy of treating clinical symptoms in SCZ.Trial Registration Number: The trial was registered with www.clinicaltrials.gov (NCT00686140)., (© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)