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Background: Andexanet alfa (andexanet) is the only Food and Drug Administration-approved antidote for direct FXa (factor Xa) inhibitors but has been reported to cause resistance to unfractionated heparin (UFH). This has delayed anticoagulation for procedures requiring cardiopulmonary bypass. The mechanism, andexanet and UFH dose dependence, and thrombotic risk of andexanet-associated heparin resistance are unknown., Methods: The effect of andexanet in vitro was determined using activated clotting times and thromboelastography. Ex vivo cardiopulmonary bypass circuits were used to determine whether andexanet impaired anticoagulation for extracorporeal circulation. Kinetics of AT (antithrombin) inhibition of FXa and thrombin were measured in the presence of andexanet. Equilibrium modeling and thrombin generation assay validation were used to predict the role of andexanet, AT, and UFH concentrations in andexanet-associated heparin resistance., Results: Andexanet prevented UFH-mediated prolongation of activated clotting times and thromboelastography times. At lower concentrations of andexanet, heparin resistance could be overcome with suprapharmacologic doses of UFH, but not at higher andexanet concentrations. Andexanet rendered standard doses of UFH inadequate to prevent circuit thrombosis, and suprapharmacologic UFH doses were only partially able to overcome this. Scanning electron microscopy demonstrated coagulation activation in circuits. Andexanet prevented UFH enhancement of AT-mediated inhibition of FXa and thrombin. Equilibrium modeling and thrombin generation assay validation demonstrated that andexanet creates a triphasic equilibrium with UFH and AT: initial UFH unresponsiveness, normal UFH responsiveness when andexanet is depleted, and finally AT depletion. Sufficient cardiopulmonary bypass heparinization can only occur at low therapeutic andexanet doses and normal AT levels. Higher andexanet doses or AT deficiency may require high UFH doses and potentially AT supplementation., Conclusions: Andexanet causes heparin resistance due to redistribution of UFH-bound AT. If andexanet cannot be avoided before heparinization and direct thrombin inhibitors are undesirable, our in vitro study suggests excess UFH should be considered as a potential strategy before AT supplementation.

We present a minimally invasive technique for deep brain hematoma evacuation that combines 3-dimensional visualization through 3DSlicer and laser-guided navigation, providing a practical and cost-effective alternative to traditional navigation in resource-limited settings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

This study was intended to determine whether rapid rehabilitation nursing can enhance postoperative rehabilitation and life quality for breast cancer (BC) patients. One hundred seventy-two patients with BC treated in our hospital from March 2020 to September 2022 were included in this retrospective study and divided into the observation group (n = 86) and control group (n = 86) based on the different nursing methods that they received. The control group accepted routine nursing care, and the observation group accepted rapid rehabilitation nursing intervention. The amount of intraoperative blood loss, anesthesia awake time, postoperative drainage tube removal time, postoperative time of getting out of bed, length of hospital stays, incidence of postoperative complications, and postoperative recovery rate of affected limb, Barthel index and quality of life instruments for cancer patients: breast cancer (QLICP-BR) of BC patients were analyzed. The amount of intraoperative bleeding in the observation group was less, and the difference was statistically significant (P < .05). The awake time of anesthesia, the time of pulling out the drainage tube after operation, the time of getting out of bed after operation and the time of hospitalization in the observation group were significant shorter (P < .05). The incidence of postoperative complications in the observation group was notably lower (P < .05). The excellent and good rate of postoperative rehabilitation of the affected limbs in the observation group was notably higher (P < .05). Before nursing, there exhibited no notable difference in the scores of Barthel index (P > .05). After 10 days of nursing, the score of Barthel index in the observation group was notably higher (P < .05). After 10 days of nursing, the QLICP-BR score of the observation group was significant higher (P < .05). Rapid rehabilitation nursing is beneficial to reduce the intraoperative blood loss of BC patients, shorten the recovery time of anesthesia, promote the excellent and good rate of rehabilitation of affected limbs, and improve the quality of life., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Primary plasma cell leukemia is a rare and highly aggressive malignancy of the blood system, with rapid disease progression and a high early mortality rate. Currently, there is no recognized therapeutic regimen, leading to the adoption of strategies typically utilized for multiple myeloma, which, however, exhibit limited efficacy. Selinexor is considered effective in treating relapsed/refractory multiple myeloma, but there are currently no reports on its application in primary plasma cell leukemia. Here, we reported a case of primary plasma cell leukemia with multiple high-risk genetic factors (including 1q21+, 17p-, and 13q-) who received a chemotherapy regimen including selinexor, pomalidomide, and dexamethasone., Patient Concerns: This case was a 58-year-old male presenting with lower back pain, abdominal pain, and various systemic symptoms., Diagnoses: The initial diagnosis of intestinal obstruction at a local hospital was followed by a referral to our emergency department due to abnormal blood test results indicative of a hematologic disorder. Further investigations confirmed a rare diagnosis of primary plasma cell leukemia of the IgA-k light chain subtype., Interventions: The patient was promptly treated with a chemotherapy regimen comprising selinexor, pomalidomide, and dexamethasone in addition to supportive care., Outcomes: Subsequent assessments showed a significant response to treatment, with improvement in symptoms, normalization of blood parameters, and achievement of very good partial response. However, due to financial constraints, the patient declined hematopoietic stem cell transplantation and eventually opted to discontinue treatment, leading to disease progression., Lessons: The combination of selinexor with pomalidomide and dexamethasone has shown good efficacy in primary plasma cell leukemia with high-risk genetic abnormalities. Our case may provide evidence for developing an effective selinexor-based regimen for treating primary plasma cell leukemia with high-risk genetic abnormalities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study investigates the efficacy and safety of transurethral prostate laser resection (HoLEP) with preservation of the urethral mucosa from the bladder neck to the tip of the prostate for the treatment of benign prostatic hyperplasia (BPH). A retrospective study was conducted on 208 patients with BPH treated at our hospital. In the control group, the urethral mucosa from the bladder neck to the tip of the prostate was not retained during surgery to ensure maximum removal of possible diseased tissue. The urethral mucosa was preserved in the observation group, which was finely separated to avoid injury, in order to protect urinary control function to the greatest extent and reduce postoperative complications. The surgical-related indicators, urinary function, sexual function, quality of life (QOL), and occurrence of postoperative complications were compared between the 2 groups of patients. After the procedure, both groups of patients experienced an increase in maximum flow rate and a decrease in residual urine volume (P < .05). The observation group showed a higher immediate postoperative urinary continence rate of 98.23% compared to 85.26% in the control group (P < .05). After the procedure, both groups of patients exhibited a significant increase in International index of erectile function-5 scores (P < .05). The retrograde ejaculation rates were compared between the 2 groups of patients before the procedure (P > .05). After the procedure, the occurrence rate of retrograde ejaculation decreased in both groups of patients, with the observation group being lower than the control group (P < .05). The International prostate symptom score (IPSS) scores and QOL scores were compared between the 2 groups of patients before and after the procedure (P > .05). After the procedure, both groups of patients showed a decrease in IPSS scores and QOL scores compared to before the procedure (P < .05). The occurrence of complications such as urethral injury, urinary incontinence, urinary retention, and postoperative bleeding was compared between the 2 groups of patients (P > .05). The efficacy and safety of performing HoLEP treatment for BPH patients with preservation of the urethral mucosa from the bladder neck to the tip of the prostate are comparable to those without preservation. However, it can improve immediate urinary continence rate and reduce retrograde ejaculation rate., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Surgical resection is the cornerstone of treatment for locally advanced gastric cancer (LAGC). Hence, downstaging of the tumor with neoadjuvant therapy is critical for R0 resection and prolongs the overall survival. Data from related studies are lacking, and the literature is scarce. Therefore, a single arm-study was performed on PD-1 inhibitor and apatinib plus S-1 and oxaliplatin as neoadjuvant chemotherapy for patients with LAGC. The findings are expected to serve as a reference for neoadjuvant therapy for LAGC. We assessed 130 LAGC patients using PD-1 inhibitor, apatinib plus S-1, and oxaliplatin as neoadjuvant chemotherapy from January 2021 to October 2022. A total of 104 patients received gastric transcatheter chemoembolization (GTC). The primary endpoint was the rate of clinical complete response, pathological complete response, and safety, while the secondary endpoints were the R0 resection rate and objective response rate of the disease and the disease control rate. A total of 130 patients completed the clinical assessment, of which 6 patients (4.6%) achieved clinical complete response, 87 patients (66.9%) achieved partial response, 30 patients (23.0%) achieved stable disease, and 7 patients (5.5%) experienced progressive disease. The overall response rate was 71.5% (93/130), and the disease control rate was 94.5% (123/130). A remarkable downstaging effect was observed in this study. Downstaging of the T stage and N stage was achieved in 71.5% and 80% of the patients, respectively, which translated into a high R0 resection rate. The findings revealed that 125 patients underwent R0 resection, and the R0 resection rate was 96.1%. According to the observed results, 21.6% of the patients achieved pathological complete response after neoadjuvant chemotherapy. Gastric transcatheter chemoembolization in the first cycle of neoadjuvant therapy was beneficial for tumor regression (P < .001). All adverse events were relieved and disappeared after symptomatic treatment, and no grade 4 adverse events were noted. PD-1 inhibitor and apatinib plus S-1 and oxaliplatin are safe and effective as neoadjuvant treatment of LAGC. Gastric transcatheter chemoembolization is useful for tumor regression during neoadjuvant therapy., 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 the Author(s). Published by Wolters Kluwer Health, Inc.)

Increasingly, the shared risk factors and pathological processes of atherosclerosis and abdominal aortic aneurysm (AAA) are being recognized. The aim of our study was to identify the hub genes involved in the pathogenesis of atherosclerosis and AAA. The analysis was based on 2 gene expression profiles for atherosclerosis (GSE28829) and AAA (GSE7084), downloaded from the Gene Expression Omnibus database. Common differential genes were identified and an enrichment analysis of differential genes was conducted, with construction of protein-protein interaction networks, and identification of common hub genes, and predicted transcription factors. The analysis identified 133 differentially expressed genes (116 upregulated and 17 downregulated), with the enrichment analysis identifying a potential important role of integrins and chemokines in the common immune and inflammatory responses of atherosclerosis and AAA. Regulation of the complement and coagulation cascades and regulation of the actin cytoskeleton were associated with both diseases, with 10 important hub genes identified: TYROBP, PTPRC, integrin subunit beta 2, ITGAM, PLEK, cathepsin S, lymphocyte antigen 86, ITGAX, CCL4, and FCER1G. Findings identified a common pathogenetic pathway between atherosclerosis and AAA, with integrin-related genes playing a significant role. The common pathways and hub genes identified provide new insights into the shared mechanisms of these 2 diseases and can contribute to identifying new therapeutic targets and predicting the therapeutic effect of biological agents., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The present study aimed to investigate the therapeutic effects of electroacupuncture (EA) on chronic cerebral hypoperfusion (CCH). We first applied the Morris water maze approach to determine the effects of EA and TGN-020 [an inhibitor of aquaporin 4 (AQP4)] on the learning and memory ability of CCH rats. The hematoxylin and eosin, and Nissl staining were further used to investigate the effects of EA and TGN-020 on the neuropathological changes of the dentate gyrus. Next, the ELISA kits were adopted to determine the effects of EA and TGN-020 on the content of amyloid-beta (Aβ) in the cerebrospinal fluid of CCH rats. Finally, we respectively employed technologies of immunohistochemical staining, quantitative real-time PCR, and Western blot to further explore the effects of EA and TGN-020 on the mRNA expression level of amyloid precursor protein (APP) and AQP4 as well as the protein expression level of Aβ1-42 and AQP4 in the dentate gyrus of CCH rats. Our results indicated that EA not only enhanced the learning and memory abilities of CCH rats but also improved the neuropathological damages of CCH rats by upregulating the mRNA and protein expression level of AQP4 to reduce the accumulation of Aβ, especially for the reduction of the mRNA expression level of APP and the protein expression level of Aβ1-42, but TGN-020 effectively reversed the therapeutic effects mentioned above of EA. In summary, we proved that EA, as the activator of AQP4, prevents the accumulation of Aβ during the treatment of CCH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study investigated the impact of endoscopic transnasal pituitary adenoidectomy on function and discussed the factors that contribute to postoperative pituitary function. To provide a foundation for protecting pituitary function and improving the curative effect of pituitary adenoma neuroendoscope resection., Methods: From January 2019 to January 2022, in the Neurosurgery Pituitary Tumor Diagnosis and Treatment Research Center, the First Affiliated Hospital of Shenzhen University, the clinical data of 306 patients who underwent endoscopic transnasal pituitary adenoma surgery were analyzed retrospectively. The surgical treatment strategy was discussed and explored, while the factors related to pituitary function were examined based on tumor size and Knosp grade., Results: There were 40 cases (67.8%) of pituitary-thyroid axis, 18 cases (60%) of pituitary-adrenal axis, 25 cases (45.4%) of pituitary-gonad axis, 5 cases (62.5%) of pituitary-growth hormone axis, and 8 cases (72.7%) of diabetes insipidus with postoperative improves of hypopituitarism. Postoperative newly developed hypopituitarism occurred in 20 cases (8.1%) of pituitary-thyroid axis, 15 cases (5.4%) of pituitary-adrenal axis, 10 cases (4.0%) of pituitary-gonad axis, 5 cases (1.7%) of pituitary-growth hormone axis, and 8 cases (2.7%) of new diabetes insipidus. The incidence of pituitary-adrenal axis hypofunction in giant pituitary adenomas was significantly higher than that in microadenomas and macroadenomas (P<0.05). The incidence of hypopituitarism of Knosp grade 4 pituitary adenoma before operation was higher than that of other groups (P<0.05), but there was no significant difference in the incidence of new hypopituitarism after operation (P>0.05)., Conclusions: In endoscopic transnasal pituitary adenoma surgery, the incidence of hypothyroidism and adrenal gland dysfunction is higher than in other hormone axes, but the recovery rate is also higher, and the recovery rate of sex hormones is lower. The incidence of postoperative hypothyroidism increases dramatically with tumor size and tumor invasiveness., 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 by Mutaz B. Habal, MD.)

Background: The development of aortic dissection (AD) is closely associated with inflammation. The Trem2 (triggering receptor expressed on myeloid cells 2)/Tyrobp (TYRO protein tyrosine kinase-binding protein) signaling pathway critically regulates innate immunity and has emerged as an important target in cardiovascular diseases; however, its role in AD remains unclear., Methods: Transcriptome data from human and mouse ADs were used to perform differentially expressed gene-based protein-protein interaction network analyses. Tyrobp knockout (Tyrobp -/- ), myeloid cell-specific Tyrobp -/- (Tyrobp fl/fl Lyz2 cre ), and Trem2 knockout (Trem2 -/ - ) mice were given β-aminopropionitrile monofumarate in drinking water to induce AD. To dissect the role of macrophages in Tyrobp deficiency-mediated AD progression, macrophages were depleted using clodronate liposomes. Bulk and single-cell RNA sequencing, immunofluorescence staining, and quantitative real-time polymerase chain reaction were performed to assess inflammation and the underlying mechanisms of Tyrobp in AD., Results: Network analysis identified Tyrobp as a hub gene of AD, with elevated levels observed in both human and mouse ADs. Global deletion and myeloid cell-specific deficiency of Tyrobp in mice significantly increased AD incidence and exacerbated extracellular matrix degradation and macrophage infiltration within the aortic wall. Macrophage depletion mitigated the adverse effects of Tyrobp deficiency on AD progression. Additionally, Tyrobp deficiency enhanced TLR (Toll-like receptor)-4 signaling and macrophage activation, which were abrogated by TLR4 inhibitors. Furthermore, deletion of the Tyrobp-associated receptor Trem2 significantly aggravated mouse AD development, whereas Trem2 agonist treatment conferred protection against AD., Conclusions: Our findings suggest a novel role for the Trem2/Tyrobp axis in AD development in mice. Enhancement of Trem2/Tyrobp signaling may represent a promising strategy for the prevention and treatment of AD. Future studies to clarify the role of Trem2/Tyrobp in human AD are warranted.

Background: This study aimed to investigate the associations of 2 preoperative muscle-related parameters, the third lumbar vertebra skeletal muscle index (L3 SMI) for muscle mass and the Hounsfield unit average calculation (HUAC) for muscle density, with the occurrence of postoperative complications among patients undergoing colorectal tumor resection surgery under general anesthesia. We hypothesized that muscle-related parameters are associated with the occurrence of postoperative complications., Methods: This was a single-center, retrospective observational study. Adult patients who underwent colorectal tumor resection surgery under general anesthesia between 2018.09.01 and 2021.09.01 were enrolled. The last abdominal computed tomography (CT) scan images obtained within 3 months before surgery were used to calculate the L3 SMI and HUAC. The primary outcome was defined as the occurrence of any postoperative complications corresponding to Clavien-Dindo classification before discharge. The secondary outcome was defined as the occurrence of any severe postoperative complications (Clavien-Dindo grade ≥3) before discharge. Multivariable logistic regression analyses were used to estimate the association between muscle-related parameters and incidence of postoperative complications. Patients' baseline demographics, past medical history and intraoperative parameters were adjusted in the multivariable logistic regression analysis., Results: A total of 317 patients with a median age of 66 (58-72) years were included. Sarcopenia (muscle mass reduction) patients in our cohort and myosteatosis (muscle density decline) were present in 254 (80.1 %) and 79 (24.9%) patients, respectively. A total of 135 patients (42.6 %) developed postoperative complications. According to the multivariable logistic regression, myosteatosis (odds ratio [OR], 1.8, 95% confidence interval [CI], 1.0-3.3, P = .039) was significantly associated with postoperative complications., Conclusions: A significant association was observed between myosteatosis and postoperative complications (corresponding to Clavien-Dindo classification before discharge), especially severe postoperative complications (Clavien-Dindo grade ≥3) in patients undergoing colorectal tumor resection. Screening for myosteatosis with HUAC using the CT before surgery may help clinicians identify high-risk perioperative patients early., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Myocardial Injuries, such as myocardial infarction, trigger complex biological responses. The epicardium, known for its regenerative capabilities, plays a pivotal role in cardiac repair by undergoing activation and subsequent cellular transformations. This review examines the mechanisms of epicardial activation after myocardial injury, focusing on epithelial-mesenchymal transition, cell proliferation, and cell migration. It underscores the significance of the epicardium in heart repair processes and discusses potential implications for developing novel cardiac therapies. These insights may pave the way for leveraging epicardial cell dynamics to enhance cardiac regeneration, ultimately reducing the morbidity associated with heart disease., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The study aimed to assess the role of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) radiomics combined with clinical features using machine learning (ML) in predicting sarcopenia and prognosis of patients with diffuse large B-cell lymphoma (DLBCL)., Methods: A total of 178 DLBCL patients (118 and 60 applied for training and test sets, respectively) who underwent pretreatment 18F-FDG PET/CT were retrospectively enrolled. Clinical characteristics and PET/CT radiomics features were analyzed, and feature selection was performed using univariate logistic regression and correlation analysis. Sarcopenia prediction models were built by ML algorithms and evaluated. Besides, prognostic models were also developed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified., Results: Fourteen features were finally selected to build sarcopenia prediction and prognosis models, including two clinical (maximum standard uptake value of muscle and BMI), nine PET (seven gray-level and two first-order), and three CT (three gray-level) radiomics features. Among sarcopenia prediction models, combined clinical-PET/CT radiomics features models outperformed other models; especially the support vector machine algorithm achieved the highest area under curve of 0.862, with the sensitivity, specificity, and accuracy of 79.2, 83.3, and 78.3% in the test set. Furthermore, the consistency index based on the prognostic models was 0.753 and 0.807 for PFS and OS, respectively. The enrolled patients were subsequently divided into high-risk and low-risk groups with significant differences, regardless of PFS or OS (P < 0.05)., Conclusion: ML models incorporating clinical and PET/CT radiomics features could effectively predict the presence of sarcopenia and assess the prognosis in patients with DLBCL., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study investigates the clinical efficacy of Tiaoshu Anshen Decoction in treating insomnia characterized by spleen and stomach Qi dysfunction. According to the differences of previous treatment, 94 patients were divided into treatment group and control group. The treatment group was treated with Tiaoshu Anshen Decoction, and the control group was treated with oral esazolam for 2 weeks. We compared serum levels of 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), DASS-21, and HAMD scores before and after treatment. We also evaluated gastrointestinal function, traditional Chinese medicine syndrome scores, quality of life, and adverse reactions, with statistical analysis conducted using SPSS 25.0. The overall efficacy and clinical outcomes were comparable between the 2 groups. Both groups showed increased serum factor levels and decreased Pittsburgh Sleep Quality Index (PSQI), HAMD, and DASS-21 scores post-treatment. Notably, the treatment group exhibited significant improvement in stool consistency, digestive symptoms, DOB < 4 and DOB ≥ 4 distribution, and TCM syndrome scores, outperforming the control group. No adverse reactions were reported in either group. This study suggests that spleen and stomach Qi dysfunction significantly contribute to insomnia, affecting its occurrence, type, and severity. Tiaoshu Anshen Decoction effectively enhances 5-HIAA, 5-HT, NE, and DA levels, reduces inflammatory factors, and improves sleep quality, gastrointestinal function, and overall quality of life. The decoction may exert its effects by regulating Qi dynamics and gastrointestinal function, indicating the gastrointestinal system as a potential key target in treating sleep disorders., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to develop and validate a prognostic model for elderly patients with differentiated thyroid carcinoma (DTC) based on various demographic and clinical parameters in order to accurately predict patient outcomes. Patients who were diagnosed with DTC and were over 55 years old between 2010 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The patients were then randomly divided into a training set and a validation set in a 7:3 ratio, and patients from our center were included as an external validation group. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors, which were then utilized to develop nomograms for predicting the prognosis. The discriminative ability of the nomograms was evaluated using the concordance index, and the calibration was assessed using calibration plots. The clinical usefulness and benefits of the predictive models were determined through decision curve analysis. The findings of the stepwise Cox regression analysis revealed that several variables, including age, marital status, sex, multifocality, T stage, N stage, and M stage, were significantly associated with overall survival in elderly patients with DTC. Additionally, age, tumor size, multifocality, T stage, N stage, and M stage were identified as the primary determinants of cancer specific survival in elderly patients with DTC. Using these predictors, nomograms were constructed to estimate the probability of overall survival and cancer specific survival. The nomograms demonstrated a high level of predictive accuracy, as evidenced by the concordance index, and the calibration plots indicated that the predicted outcomes were consistent with the actual outcomes. Furthermore, the decision curve analysis demonstrated that the nomograms provided substantial clinical net benefit, indicating their utility in clinical practice., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To study the changes of lymphocyte subsets in children with acute lymphoblastic leukemia (ALL) at initial diagnosis and compare them with those of healthy children and patients who have achieved complete remission (CR). Furthermore, we aim to analyze the prognostic significance of lymphocyte subsets in these patients. From May 2011 to December 2015, 405 children with ALL were enrolled in this study. Peripheral blood was collected at the time of diagnosis, and lymphocyte subsets were detected by flow cytometry. Then, the percentages of lymphocyte subsets in each group were compared. In addition, survival and prognostic factor analyses were performed to determine the prognostic value of lymphocyte subsets. Lymphocyte subsets in children with ALL were dramatically different from those in healthy children and patients achieving CR. Additionally, lymphocyte subsets were correlated with different minimal residual disease and risk parameters. Furthermore, percentages of CD3+ T cells and CD4+ T cells and the ratio of CD4/CD8 were associated with different clinical outcomes. Multivariate analysis demonstrated the percentage of CD4+ T cell as an independent predictor for clinical prognosis. Lymphocyte subsets in pediatric ALL undergo dramatic changes and were related to prognosis, especially CD4+ T cells., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: The authors declare no conflicts of interest.

Objective: This study aimed to investigate the association between rare earth elements (REEs) and metabolic syndrome (MetS)., Methods: We used a cross-sectional design based on the baseline data of the Prospective Cohort Study of Chronic Diseases in Ethnic Minority Natural Population in Guangxi in China. Logistic regression and BKMR models were employed to evaluate the association between REEs and risk of MetS., Results: Although REEs were not significantly associated with MetS, certain elements such as La, Pr, and Nd were negatively associated with abdominal obesity, whereas Ce, Pr, Nd, and Dy were positively associated with hypertension. BKMR models suggested a U-shaped relationship between mixed REEs and MetS, with varying effects on abdominal obesity and high blood pressure., Conclusions: This study suggests that exposure to REEs may be associated with a reduced risk of abdominal obesity and an increased risk of high blood pressure., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Background: Hepatic ischemia/reperfusion (I/R) injury is a major cause of complications in clinical liver surgery. AXL receptor tyrosine kinase (AXL) is a member of the TAM receptor tyrosine kinase family (TYRO3, AXL, and MERTK). Our previous study has shown that AXL expression was markedly upregulated in liver transplantation patients. However, the underlying mechanism of AXL in hepatic I/R injury remains unclear., Methods: A mouse liver warm I/R model and a primary hepatocyte hypoxia/reoxygenation model were established to investigate the role of AXL activation and ferroptosis in hepatic I/R injury by pretreating with recombinant mouse growth arrest-specific protein 6 (AXL activator) or R428 (AXL inhibitor). Moreover, we used LY294002 (phosphatidylinositol 3-kinase [PI3K] inhibitor) to evaluate the relationship between the PI3K/AKT (the Ser and Thr kinase AKT) pathway and ferroptosis in hepatic I/R injury., Results: Hepatic I/R injury decreased phosphorylation AXL expression and enhanced ferroptosis in liver transplantation patients and hepatic I/R-subjected mice. AXL activation attenuated lipid peroxidation and ferroptosis in hepatic I/R injury in vivo and in vitro. Inhibition of AXL activation exacerbated liver pathological damage and liver dysfunction, as well as iron accumulation and lipid peroxidation in hepatic I/R injury. Mechanistically, activated growth arrest-specific protein 6/AXL and its downstream PI3K/AKT signaling pathway inhibited ferroptosis during hepatic I/R injury., Conclusions: AXL activation protects against hepatic I/R injury by preventing ferroptosis through the PI3K/AKT pathway. This study is the first investigation on the AXL receptor and ferroptosis, and activating AXL to mitigate ferroptosis may be an innovative therapeutic strategy to combat hepatic I/R injury., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The aim of this study was to investigate whether using an innervated vascularized iliac bone flap could effectively prevent bone resorption and maintain sensory function in the lower lip., Methods: In the innervated group, the deep circumflex iliac artery and recipient vessels were anastomosed, with simultaneous microanastomosis of ilioinguinal nerve, mental nerve, and inferior alveolar nerve. Conversely, the control group underwent solely vascular anastomosis. Computed tomography was used to assess bone quality. Sensory recovery of the lower lip was recorded using 2-point discrimination and current perception threshold testing., Results: The study comprised a total of 40 subjects, with each group accounting for 20 participants, equally distributed in terms of gender. Hounsfield unit loss was significantly lower in the innervated group (13.26% ± 8.65%) as compared with the control group (37.98% ± 8.60%) ( P < 0.001). Moreover, 2-point discrimination values were lower in the innervated group (15.11 ± 8.39 mm) when compared with the control group (21.44 ± 7.24 mm) ( P = 0.02). The current perception threshold values for the innervated group were 176.19 ± 31.89, 64.21 ± 19.23, and 42.29 ± 18.96 at 2 kHz, 250 Hz, and 5 Hz, respectively, whereas in the control group, the current perception threshold values were 204.47 ± 36.99, 82.26 ± 27.29, and 58.89 ± 25.38 at 2 kHz, 250 Hz, and 5 Hz ( P = 0.02, P = 0.02, and P = 0.03, respectively)., Conclusion: The innervated vascularized iliac bone flap represents a safe and effective novel approach to preserving lower lip sensation and preventing bone resorption through functional mandibular reconstruction., Clinical Question/level of Evidence: Therapeutic, I., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Background: Recent evidence indicates that general anesthesia and sleep-wake behavior share some overlapping neural substrates. GABAergic neurons in the central amygdala (CeA) have a high firing rate during wakefulness and play a role in regulating arousal-related behaviors. The objective of this study is to investigate whether CeA GABAergic neurons participate in the regulation of isoflurane general anesthesia and uncover the underlying neural circuitry., Methods: Fiber photometry recording was used to determine the changes in calcium signals of CeA GABAergic neurons during isoflurane anesthesia in Vgat-Cre mice. Chemogenetic and optogenetic approaches were used to manipulate the activity of CeA GABAergic neurons, and a righting reflex test was used to determine the induction and emergence from isoflurane anesthesia. Cortical electroencephalogram (EEG) recording was used to assess the changes in EEG spectral power and burst-suppression ratio during 0.8% and 1.4% isoflurane anesthesia, respectively. Both male and female mice were used in this study., Results: The calcium signals of CeA GABAergic neurons decreased during the induction of isoflurane anesthesia and was restored during the emergence. Chemogenetic activation of CeA GABAergic neurons delayed induction time (mean ± SD, vehicle vs. clozapine-N-oxide: 58.75±5.42 s vs. 67.63±5.01 s; n=8, P=0.0017) and shortened emergence time (385.50±66.26 s vs. 214.60±40.21 s; n=8, P=0.0017) from isoflurane anesthesia. Optogenetic activation of CeA GABAergic neurons produced a similar effect. Furthermore, optogenetic activation decreased EEG delta power (Pre-stim vs. Stim: 46.63%±4.40% vs. 34.16%±6.47%; n=8, P=0.0195) and burst-suppression ratio (83.39%±5.15% vs. 52.60%±12.98%; n=8, P=0.0002). Moreover, optogenetic stimulation of terminals of CeA GABAergic neurons in the basal forebrain (BF) also promoted cortical activation and accelerated behavioral emergence from isoflurane anesthesia., Conclusions: Our results suggest that CeA GABAergic neurons play a role in general anesthesia regulation, which facilitates behavioral and cortical emergence from isoflurane anesthesia through the GABAergic CeA-BF pathway., Competing Interests: Conflicts of Interest: The authors have no competing financial interests or potential conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists.)

Carriers with germline breast cancer 1/2 gene mutations (BRCAm) are likely to develop ovarian cancer (OC). Therefore, identifying these mutations may enable individualized therapy for OC and preventive measures to reduce OC risk in BRCAm carrier families. Thus, we investigated the prevalence of BRCAm in OC patients from Yunnan Province in Southwest China. In total, 674 unselected OC patients were enrolled and tested for BRCAm via next-generation sequencing. Data on clinicopathological characteristics and personal/family history of cancer were collected. The prevalence rates of pathogenic/likely pathogenic BRCAm were 26.6% overall, 20.8% among BRCA1m carriers, 5.5% among BRCA2m carriers, and 0.3% among carriers of both BRCA1m and BRCA2m. The most common pathogenic mutation in the BRCA1 gene was c.5114T>C (n = 9). The number of BRCAm carriers was significantly greater among patients with serous cancer, a personal tumor history, a family history of hereditary breast and ovarian cancer (HBOC)-related tumors, and bilateral tumors. The most common pathogenic mutation in this cohort was c.5114T>C (n = 9) in BRCA1. The prevalence and spectrum of BRCAm in OC patients from Yunnan Province are different from those in other groups. BRCA status testing is advised for all OC patients, particularly those with a family history of HBOC., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Poststroke cognitive impairment and dementia (PSCID) is a major cause of stroke-related morbidities and mortalities. Over the last few years, there has been growing evidence supporting the effectiveness of needle-related treatments in PSCID. Our goal was to rate the included therapies and assess the clinical effectiveness of various needle-related treatments in patients with PSCID., Methods: We searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed), Wanfang, FDA.gov, and ClinicalTrials.gov. A mix of subject terms and free words was used to search the databases. The retrieval period was from the inception date of the database to February, 2023. We included SRs and MAs from acupuncture RCTs of patients with PSCID. The Cochrane Risk Assessment Scale was used to evaluate the risk of bias in the included studies. State 17.0 was used for network meta-analysis in accordance with the Bayesian framework., Results: There were 34 studies total of 2690 patients. The cumulative ranking curve (SUCRA) revealed that CT + CFT + EA was the most efficient intervention to improve (Mini-Mental State Examination, MMSE) efficiency, followed by CT + CFT + AP to improve (Montreal Cognitive Assessment, MoCA) efficiency, CT + CFT + ACU for improving (Activities of Daily Living scale, ADL) scores, and CT + CFT + EA to improve clinical efficiency., Conclusion: The results show that Different acupuncture methods can improve cognitive function and daily living ability in patients with PSCID. Network meta-analysis revealed that both CT + CFT + ACU and CT + CFT + EA appeared to be more beneficial for daily living activities, while CT + CFT + EA and CT + CFT + AP appeared to be more helpful for cognitive performance in patients with PSCID. Treatments including acupuncture are safer and have a reduced incidence of negative side effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To retrospectively explore the role of magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in analyzing the corticospinal tract injury in acute cerebral anterior circulation infarction in the basal ganglia region and the correlation between DTI parameters and neurological function scores, patients with acute cerebral infarction and stroke had undergone plain MRI and DTI sequence scanning were enrolled. Diffusion tensor tractography was used to perform 3-dimensional reconstruction of bilateral corticospinal tracts (CST). The image data were processed to obtain fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values, and the correlation between the DTI parameters and neurological function scores of National Institutes of Health Stroke Scale (NIHSS) was evaluated. A total of thirty-two patients with acute ischemic cerebral infarction were retrospectively enrolled, including 19 males and 13 females with a mean age 63.22 ± 7.78 years. The CST score was 0 in 2 (6.25%) patients, 1 in 9 (28.13%), 2 in 9 (28.13%), 3 in 7 (21.88%), and 4 in 5 (15.63%). The FA value significantly (P = .01) decreased (0.52 ± 0.03 vs 0.62 ± 0.04) on the ischemic side compared with that on the normal side. A significant (P < .05) difference was detected in the number of nerve fibers (223.3 ± 110.0 vs 246.7 ± 104.4) rather than in the ADC values (0.86 ± 0.06 vs 0.84 ± 0.06) between the ischemic and healthy sides. The FA and ADC values were not significantly (P > .05) different according to the CST scores 0, 1, 2, 3, or 4 between the ischemic and healthy sides. There was a significant (P < .05) negative correlation between the FA value on the infarcted side and the NIHSS score. In conclusion, with the DTI technology, varying degrees of damage to the corticospinal tract at the infarcted side can be detected and important clinical information can be provided for the diagnosis and prognosis of acute cerebral infarction by evaluating the degree of corticospinal tract injury., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Genetic factors play a significant role in the development of congenital heart disease (CHD). Many studies on the genetics of CHD have been published worldwide; however, no research has assessed and mapped the global research landscape of these studies. This bibliometric and visualized study aimed to delineate research hotspots and trends in the field of CHD genetics. Scientific papers on the genetics of CHD from January 1, 1950, to December 31, 2023, were obtained by searching the Web of Science Core Collection. The bibliometric metadata of each chosen research paper were extracted, analyzed, and visualized using tools such as Microsoft Excel 2021, VOSviewer, and CiteSpace. The final analysis included 5317 papers discussing the genetics of CHD. The countries and journals that published the highest number of papers were the United States (n = 2118), and American Journal of Medical Genetics Part A (n = 332), respectively. In addition to CHD and genetics, keywords such as tetralogy of Fallot, ventricular septal defect, and atrial septal defect appeared most frequently among 8365 keywords. Eight clusters were formed to categorize the keywords. Keywords such as case-control study, whole genome sequencing, and whole exome sequencing in clusters 6, 7, and 8, respectively, had the latest average publication year among all clusters. To the best of our knowledge, this is the first bibliometric analysis of CHD genetics studies. Tetralogy of Fallot, ventricular septal defect, and atrial septal defect are global research topics. The interactions between environmental and genetic factors in the pathogenesis of CHD, genetic etiology of CHD-associated pulmonary arterial hypertension, and molecular genetics of CHD via high-throughput genomic technology are possible areas of future research on the genetics of CHD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To examine the association between the combination of central and general obesity measures and the risk of pelvic organ prolapse (POP)., Methods: Waist/height ratio and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) for 251,143 participants (aged 39-71 years) without pre-existing POP from the UK Biobank were collected at enrollment between 2006 and 2010. Participants were followed through December 19, 2022. Incident POP was identified using International Classification of Diseases, Tenth Revision codes and operating procedure codes in the medical records. Cox proportional hazards model was used to estimate the association between obesity measures and incident POP. Population-attributable fractions were calculated to indicate the proportion of cases that were attributable to obesity measures., Results: During a median follow-up of 13.8 years, 9,781 POP cases were recorded. Central obesity (waist/height ratio 0.5 or greater) was associated with a 48% increased risk of POP regardless of BMI (hazard ratio [HR] 1.48; 95% CI, 1.41-1.56). Approximately 21.7% (95% CI, 19.1-24.4%) of all POP cases were attributable to central obesity. In addition, overweight without central obesity (BMI 25-29.9 and waist/height ratio less than 0.5) was associated with a 23% higher risk of POP (HR 1.23; 95% CI, 1.14-1.34), and this accounted for 2.0% (95% CI, 1.1-2.9%) of all POP cases. The magnitude of increased POP risk associated with central obesity varied by age (younger than 60 years vs 60 years or older: 57% vs 39%) and by history of hysterectomy (no vs yes: 54% vs 27%)., Conclusion: Central obesity and overweight without central obesity are risk factors for POP., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of the study is to explore the application of safety education based on the IMB model to prevent harm caused by magnetic resonance ferromagnetic projection accidents., Methods: One hundred ninety-six patients undergoing magnetic resonance imaging were divided into a control group of 90 cases and an observation group of 106 cases. The control group received routine safety education, while the observation group received safety education based on the IMB model in addition to routine education. The knowledge, attitudes, and behaviors related to the prevention of ferromagnetic projection accidents, as well as fear scores, were compared before and after the intervention., Results: A total of 90 cases in the control group and 106 cases in the observation group completed the study. There were statistically significant differences in the scores of knowledges, attitudes, and behaviors related to the prevention of ferromagnetic projection accidents, as well as fear scores between the 2 groups after the intervention (all P < 0.01)., Conclusions: Safety education based on the IMB model can improve the knowledge, attitudes, and behaviors of magnetic resonance imaging patients and reduce the risk of ferromagnetic projection accidents., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Gout, a metabolic disorder, is increasingly being linked to immune cells. However, the causal relationships between these factors remain unclear. Our study aimed to elucidate the causal relationship between immune cells and gout. Our study used 2-sample Mendelian randomization (MR) to explore the causal relationship between immune cells and gout. It is noteworthy that we utilized 5 methods MR-Egger, weighted median, inverse variance weighted, weighted mode, and simple mode to ensure the reliability of the results. Comprehensive sensitivity analyses were performed to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. After false discovery rate correction (PFDR <0.20), 3 immunophenotypes were identified: one in the B cell panel, one in the regulatory T cells panel, and another in the T lymphocytes, B lymphocytes, Natural Killer cells panel. Among them, 2 immunophenotypes (CD4-CD8-T cell absolute count and CD25 on IgD + CD24 + B cell) increased the risk of developing gout, whereas the other one immunophenotype (CD45RA + CD28- CD8 + T cell %T cell) decreased the risk of gout. Subsequently, we did not observe heterogeneity and horizontal pleiotropy stable in these data through comprehensive sensitivity analyses. Furthermore, we identified some positive results in reverse MR analysis, but after false discovery rate correction (PFDR <0.20), no significant results were detected. Our study revealed causal relationships between immune cells and gout, providing novel insights into the prevention and treatment of gout., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Thiamine deficiency is a well-known risk factor for the development of severe encephalopathy, such as Wernicke encephalopathy and Korsakoff syndrome, but the underlying mechanism is still mysterious. This study aims to investigate the expression levels of thiamine metabolism genes in different tissues and their impact on brain susceptibility to thiamine deficiency. The mRNA and protein levels of four genes known to be associated with thiamine metabolism: thiamine pyrophosphokinase-1 ( Tpk ), Solute carrier family 19 member 2 ( Slc19a2 ), Slc19a3 , and Slc25a19 , in the brain, kidney, and liver of mice were examined. Thiamine diphosphate (TDP) levels were measured in these tissues. Mice were subjected to dietary thiamine deprivation plus pyrithiamine (PTD), a specific TPK inhibitor, or pyrithiamine alone to observe the reduction in TDP and associated pathological changes. TPK mRNA and protein expression levels were lowest in the brain compared to the kidney and liver. Correspondingly, TDP levels were also lowest in the brain. Mice treated with PTD or pyrithiamine alone showed an initial reduction in brain TDP levels, followed by reductions in the liver and kidney. PTD treatment caused significant neuron loss, neuroinflammation, and blood-brain barrier disruption, whereas dietary thiamine deprivation alone did not. TPK expression level is the best indicator of thiamine metabolism status. Low TPK expression in the brain appears likely to contribute to brain susceptibility to thiamine deficiency, underscoring a critical role of TPK in maintaining cerebral thiamine metabolism and preventing thiamine deficiency-related brain lesions., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Atherosclerosis is the most common cause of cardiovascular diseases. Clinical studies indicate that loss-of-function ASGR1 (asialoglycoprotein receptor 1) is significantly associated with lower plasma cholesterol levels and reduces cardiovascular disease risk. However, the effect of ASGR1 on atherosclerosis remains incompletely understood; whether inhibition of ASGR1 causes liver injury remains controversial. Here, we comprehensively investigated the effects and the underlying molecular mechanisms of ASGR1 deficiency and overexpression on atherosclerosis and liver injury in mice., Methods: We engineered Asgr1 knockout mice ( Asgr1 -/- ), Asgr1 and ApoE double-knockout mice ( Asgr1 -/- ApoE -/- ), and ASGR1-overexpressing mice on an ApoE -/- background and then fed them different diets to assess the role of ASGR1 in atherosclerosis and liver injury., Results: After being fed a Western diet for 12 weeks, Asgr1 -/- ApoE -/- mice exhibited significantly decreased atherosclerotic lesion areas in the aorta and aortic root sections, reduced plasma VLDL (very-low-density lipoprotein) cholesterol and LDL (low-density lipoprotein) cholesterol levels, decreased VLDL production, and increased fecal cholesterol contents. Conversely, ASGR1 overexpression in ApoE -/- mice increased atherosclerotic lesions in the aorta and aortic root sections, augmented plasma VLDL cholesterol and LDL cholesterol levels and VLDL production, and decreased fecal cholesterol contents. Mechanistically, ASGR1 deficiency reduced VLDL production by inhibiting the expression of MTTP (microsomal triglyceride transfer protein) and ANGPTL3 (angiopoietin-like protein 3)/ANGPTL8 (angiopoietin-like protein 8) but increasing LPL (lipoprotein lipase) activity, increased LDL uptake by increasing LDLR (LDL receptor) expression, and promoted cholesterol efflux through increasing expression of LXRα (liver X receptor-α), ABCA1 (ATP-binding cassette subfamily A member 1), ABCG5 (ATP-binding cassette subfamily G member 5), and CYP7A1 (cytochrome P450 family 7 subfamily A member 1). These underlying alterations were confirmed in ASGR1-overexpressing ApoE -/- mice. In addition, ASGR1 deficiency exacerbated liver injury in Western diet-induced Asgr1 -/- ApoE -/- mice and high-fat diet-induced but not normal laboratory diet-induced and high-fat and high-cholesterol diet-induced Asgr1 -/- mice, while its overexpression mitigated liver injury in Western diet-induced ASGR1-overexpressing ApoE -/- mice., Conclusions: Inhibition of ASGR1 inhibits atherosclerosis in Western diet-fed ApoE -/- mice, suggesting that inhibiting ASGR1 may serve as a novel therapeutic strategy to treat atherosclerosis and cardiovascular diseases.

Objective: To compare the efficacy of traditional occlusal guides with computer-aided surgical simulation (CASS) guides in enhancing postoperative outcomes for patients with bimaxillary protrusion., Methods: This retrospective study evaluated 34 patients undergoing anterior maxillary and mandibular subapical osteotomy at the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences. Fourteen patients were treated using traditional occlusal guides, whereas 20 patients were treated with CASS guides (median age 28.6 years, median follow-up 259 days). Pre and postoperative cephalometric indicators were measured using cephalometric software. Data analysis was conducted using SPSS 14.0, with significant differences determined at P < 0.05., Results: All 34 patients experienced primary healing without complications. Follow-up indicated significant improvements in key cephalometric measurements in the CASS group compared with the traditional group, including mandibular position (SNB angle, P < 0.001), jaw relationship (ANB angle, P < 0.001), facial angle (FH-NPo, P = 0.002), and condyle-to-sella distance (Co-S, P = 0.024). The CASS group also showed better aesthetic outcomes, with significant reductions in overjet (P = 0.012), overbite (P = 0.001), and improved alignment of upper and lower incisors (U1-L1 angle, P = 0.031)., Conclusion: CASS-guided surgery offers a superior alternative to traditional methods for treating bimaxillary protrusion, providing more precise and aesthetically pleasing results. This study highlights the significant advantages of using advanced digital simulation and 3-dimensional printing technologies in orthognathic surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

The triglyceride-glucose (TyG) index is a crucial marker of insulin resistance, as evidenced by numerous studies related to metabolic diseases. This bibliometric analysis investigates research trends associated with the TyG index over the past 24 years. We collected data on TyG index publications from January 1, 2000, to January 7, 2024, using the Web of Science database. Analysis was conducted utilizing VOSviewer, Scimago Graphica, and CiteSpace to evaluate publication metrics, citations, countries, institutions, authors, journals, and keywords. A total of 1163 publications from 354 journals authored by 6149 researchers across 60 countries were analyzed. China emerged as the leading contributor, with 654 publications (56.23%). Capital Medical University was the most productive institution, and Wu Shouling was the top author. Cardiovascular Diabetology was identified as the most influential journal. Key emerging research directions include the role of the TyG index as a representative marker for insulin resistance, particularly concerning insulin sensitivity; its association with body mass index and hyperuricemia; and its diagnostic and prognostic value in nonalcoholic fatty liver disease and cardiovascular conditions such as acute coronary syndrome, carotid plaque, and hypertension. Current trends favor cohort studies predominantly involving adult populations. Overall, China leads TyG index research, focusing on its connections to insulin sensitivity, body mass index, and hyperuricemia, while the index's diagnostic and prognostic significance for nonalcoholic fatty liver disease and cardiovascular diseases represents an expanding research frontier., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Esophageal cancer (EC) poses a significant global health burden, necessitating effective treatment strategies. Immune checkpoint inhibitors have emerged as a promising therapeutic option for EC, but the identification of predictive biomarkers remains crucial for optimizing patient outcomes. We conducted a retrospective analysis of medical records from advanced esophageal squamous cell carcinoma patients treated with first-line programmed death 1 inhibitors. Peripheral blood lymphocyte subpopulations were evaluated using flow cytometry, while hematological tests provided data on neutrophil, lymphocyte, and monocyte counts. Cox regression and logistic regression analyses were employed to explore the association between lymphocyte subpopulations, baseline characteristics, and progression-free survival (PFS). Among the 100 initially included patients, 70 met eligibility criteria. Multivariate Cox regression analysis revealed a significant association between high CD16+CD56+ lymphocyte proportions and longer PFS, independent of other clinical variables. Similarly, a high CD4+/CD8+ ratio was correlated with prolonged PFS. Kaplan-Meier survival curves supported these findings. Logistic regression analysis indicated no significant differences in the CD4+/CD8+ ratio and CD16+CD56+ lymphocytes concerning baseline characteristics, suggesting their potential as independent prognostic markers. Our study highlights the predictive value of peripheral blood CD16+CD56+ lymphocytes and the CD4+/CD8+ ratio for the efficacy of programmed death 1 inhibitors in advanced esophageal squamous cell carcinoma patients. These findings underscore the importance of peripheral blood biomarkers in guiding personalized immunotherapy strategies and improving outcomes for EC patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to examine the association between constipation and mild cognitive impairment (MCI); and further elucidate the possible mechanisms involved. A cross-sectional study was conducted among community-dwelling elders (N = 789) in Nanning, China. Trained research staffs collected detailed information through questionnaires and physical examinations. A Bayesian network model was used to explore the hypothesized causal path. Synergistic effects of constipation with infrequent fruit consumption, inactive physical exercise, or history of stroke were observed in the risks of MCI occurrence. The Bayesian network model analyses showed 3 hypothesized causal-association paths leading to MCI occurrence. Among these, constipation, history of stroke, and years of schooling were directly related to the occurrence of MCI. Years of schooling indirectly affected MCI through infrequent fruit consumption and constipation; or through inactive physical exercises and history of stroke. This study demonstrates a direct association between constipation and increased risks of MCI., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to evaluate the diagnostic accuracy of 18F-fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in identifying primary tumors and mediastinal lymph node metastases in nonsmall cell lung cancer (NSCLC), with histopathological findings serving as the reference standard., Methods: Nineteen patients underwent preoperative 18F-FAPI PET/CT and subsequent surgery; of these, 13 also underwent 18F-fluorodeoxyglucose (FDG) PET/CT within 1 week. The diagnostic accuracy of primary tumors and lymph node metastases was evaluated for both modalities. Semiquantitative parameters, including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBRs), for both primary tumors and lymph node metastases were assessed for both modalities., Results: For primary tumors, 18 of 19 (94.7%) showed positive results on 18F-FAPI PET/CT scans. In 13 patients who also underwent 18F-FDG PET/CT, 18F-FAPI PET/CT demonstrated a higher detection rate compared with 18F-FDG PET/CT (100% vs. 69.1%). The overall accuracy of lymph node assessment with 18F-FAPI PET/CT (95.9-97.1%) was significantly higher compared to 18F-FDG PET/CT (51.0%). Malignant lymph nodes exhibited significantly higher SUVmax and TBR on 18F-FAPI scans (SUVmax: 7.0 vs. 0.9, P < 0.001; TBRmuscle: 5.0 vs. 0.8, P < 0.001) than on 18F-FDG scans (SUVmax: 3.9 vs. 1.8, P = 0.01), except for the liver TBR on 18F-FDG scans (TBRliver: 1.8 vs. 1.0, P = 0.055)., Conclusion: 18F-FAPI could be utilized in the preoperative staging of NSCLC to mitigate the incidence of false positives associated with 18F-FDG, due to its higher accuracy in identifying mediastinal lymph node metastasis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pulmonary hypertension is a devastating vascular disorder characterized by extensive pulmonary vascular remodeling, ultimately leading to right ventricular failure and death. Activation of PDGF (platelet-derived growth factor) signaling promotes the hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs), thus contributing to the pulmonary vascular remodeling. However, the molecular mechanisms that govern hyperproliferation of PASMCs induced by PDGF remain largely unknown, including the contribution of long noncoding RNAs (lncRNAs). In this study, we aimed to identify a novel lncRNA regulated by PDGF implicated in PASMC proliferation in pulmonary vascular remodeling., Methods: RNA-sequencing analysis was conducted to identify a novel lncRNA named vessel-enriched lncRNA regulated by PDGF-BB (VELRP). Functional investigations of VELRP were performed using knockdown and overexpression strategies along with RNA sequencing. Validation of the function and potential mechanisms of VELRP were performed through Western blot, RNA immunoprecipitation, and chromatin immunoprecipitation assays., Results: We identified a novel vessel-enriched lncRNA with an increased response to PDGF-BB stimulus. VELRP was identified as an evolutionarily conserved RNA molecules. Modulation of VELRP in PASMCs significantly altered cell proliferation. Mechanistically, VELRP enhances trimethylation of H3K4 by interacting with WDR5 (WD repeat-containing protein 5), leading to increased expression of CDK (cyclin-dependent kinase) 1, CDK2, and CDK4 and consequent hyperproliferation of PASMCs. The pathological relevance of VELRP upregulation in pulmonary artery was confirmed using rat pulmonary hypertension models in vivo, as well as in PASMCs from patients with idiopathic pulmonary arterial hypertension patients. Specific knockdown of VELRP in smooth muscle cells using adeno-associated virus type 9 SM22α (smooth muscle protein 22α) promoter-shRNA-mediated silencing of VELRP resulted in a significant decrease in right ventricular systolic pressure and vascular remodeling in rat pulmonary hypertension model., Conclusions: VELRP, as an lncRNA upregulated by PDGF-BB, mediates PASMC proliferation via WDR5/CDK signaling. In vivo studies demonstrate that targeted intervention of VELRP in smooth muscle cells can prevent the development of pulmonary hypertension.

Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study comprehensively examined the demographic and clinical characteristics of patients undergoing valproic acid therapy and explored their potential impact on plasma valproic acid concentrations. All enrolled patients were administered the extended-release formulation. An in-depth investigation of factors, including dose, age, sex, body mass index, co-administered medications, and laboratory test findings, was conducted to evaluate their potential influence on study outcomes., Methods: In total, 164 patients met the inclusion criteria and were included in the analysis. The patient age ranged from 13 to 60 years, with a median age of 25.71 years. Most patients (89%) received a daily dose of 1 g valproic acid. Co-administered psychiatric medications included aripiprazole, quetiapine, and lorazepam. Laboratory test results, such as hemoglobin and transaminase levels, were also collected as part of the study., Results: The average plasma valproic acid plasma concentration was 79.8 mg/L. The dose significantly affected valproic acid concentrations, as a higher percentage of measurements exceeded the therapeutic range at a daily dose of 1 g. Furthermore, females exhibited significantly higher valproic acid concentrations compared with males at the same dose ( P < 0.05). However, different age groups showed no statistically significant differences in valproic acid concentrations ( P > 0.05). The co-administered antipsychotic and antidepressant medications significantly affected valproate concentrations, as reflected in the multiple regression model ( P < 0.01)., Conclusions: This study offers valuable insights into the demographic and clinical characteristics of patients undergoing valproic acid therapy. It highlights the influence of dose, sex, and concomitant medications on plasma valproic acid concentrations. Overall, these findings can help guide dose adjustments and implement personalized treatment strategies in valproic acid therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The effects of oxygenation targets (partial pressure of arterial oxygen [Pa o2 ], arterial oxygen saturation [Sa o2 ]/peripheral oxygen saturation [Sp o2 ], or inspiratory oxygen concentration [Fi o2 ] on clinical outcomes in critically ill patients remains controversial. We reviewed the existing literature to assess the effects of lower and higher oxygenation targets on the mortality rates of critically ill intensive care unit (ICU) patients., Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched from their dates of inception to December 31, 2022, for randomized controlled trials (RCTs) comparing lower and higher oxygenation targets for critically ill patients ≥18 years of age undergoing mechanical ventilation, nasal cannula, oxygen mask, or high-flow oxygen therapy in the ICU. Data extraction was conducted independently, and RoB 2.0 software was used to evaluate the quality of each RCT. A random-effects model was used for the meta-analysis to calculate the relative risk (RR). We used the I 2 statistic as a measure of statistical heterogeneity. Certainty of evidence was assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines., Results: We included 12 studies with a total of 7416 patients participating in RCTs. Oxygenation targets were extremely heterogeneous between studies. The meta-analysis found no differences in mortality between lower and higher oxygenation targets for critically ill ICU patients (relative risk [RR], 1.00; 95% confidence interval [CI], 0.93-1.09; moderate certainty). The incidence of serious adverse events (RR, 0.93; 95% CI, 0.85-1.00; high certainty), mechanical ventilation-free days through day 28 (mean difference [MD], -0.05; 95%CI, -1.23 to 1.13; low certainty), the number of patients requiring renal replacement therapy (RRT) (RR, 0.96; 95% CI, 0.84-1.10; low certainty), and ICU length of stay (MD, 1.05; 95% CI, -0.04 to 2.13; very low certainty) also did not differ among patients with lower or higher oxygenation targets., Conclusions: Critically ill ICU patients ≥18 years of age managed with lower and higher oxygenation targets did not differ in terms of mortality, RRT need, mechanical ventilation-free days through day 28, or ICU length of stay. However, due to considerable heterogeneity between specific targets in individual studies, no conclusion can be drawn regarding the effect of oxygenation targets on ICU outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Objectives: The objective of this study was to investigate the dynamic profiles of myocardial injury biomarkers and their association with mortality in patients with severe fever with thrombocytopenia syndrome (SFTS)., Design: A retrospective cohort study., Settings: Union Hospital in Wuhan, China., Patients: A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis., Interventions: None., Measurements and Main Results: In total, 580 patients with SFTS were enrolled in the study, comprised of 469 survivors and 111 nonsurvivors, with a 21-day fatality rate of 19.1%. The elevation of troponin I (TnI) was observed in 61.6% patients (357/580) with SFTS upon admission, and 68.4% patients (397/580) developed an abnormal TnI level during hospitalization. Multivariate logistic regression identified age, viral load, platelet count, creatinine level, and TnI level as potential risk factors for mortality in patients with SFTS. The results of restricted cubic splines revealed that when the TnI level (baseline TnI: 1.55 [lg (ng/L+1)], peak value: TnI 1.90 [lg (ng/L+1)]) exceeded a certain threshold, the predicted mortality of patients with SFTS increased alongside the rise in TnI levels. Mortality rate surpassed 40% among patients with SFTS with TnI greater than or equal to 10 times the upper limit of normal at admission (43.8%) or during hospitalization (41.7%). Older age, a history of cardiovascular disease, and higher d -dimer levels were potential risk factors for elevated TnI levels in patients with SFTS., Conclusions: Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality., Competing Interests: Dr. Shen disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Abstract: Lack of information is cited as a source of distress for caregivers of patients with brain injury during the recovery process. This is a quality improvement project with the purpose of educating family members of brain injury patients about acute inpatient rehabilitation and providing a reliable source of information through the Model Systems Knowledge Translation Center Traumatic Brain Injury Model Systems Factsheets. The study was conducted in the brain injury unit of an acute inpatient rehabilitation facility and a total of 32 family members participated in the study. Educational sessions were provided verbally by phone based on the Model Systems Knowledge Translation Center-Traumatic Brain Injury Model Systems "Traumatic Brain Injury and Acute Inpatient Rehabilitation" Factsheet. Surveys with five confidence statements and Likert scale-graded responses were verbally administered by phone immediately before and after each educational session to evaluate for understanding. There was a statistically significant increase in confidence for all five confidence statements when comparing pre- and posteducation responses ( P < 0.05, Wilcoxon signed-rank test). This quality improvement project thereby presents an effective and feasible framework for teaching, improving communication, and providing valuable information to families early in the brain injury rehabilitation course., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear., Methods: We assessed DDX5 expression in human failing hearts and a mouse HF model. To study the function of DDX5 in heart, we engineered cardiomyocyte-specific Ddx5 knockout mice. We overexpressed DDX5 in cardiomyocytes using adeno-associated virus serotype 9 and performed transverse aortic constriction to establish the murine HF model. The mechanisms underlined were subsequently investigated using immunoprecipitation-mass spectrometry, RNA-sequencing, alternative splicing analysis, and RNA immunoprecipitation sequencing., Results: We screened transcriptome databases of murine HF and human dilated cardiomyopathy samples and found that DDX5 was significantly downregulated in both. Cardiomyocyte-specific deletion of Ddx5 resulted in HF with reduced cardiac function, an enlarged heart chamber, and increased fibrosis in mice. DDX5 overexpression improved cardiac function and protected against adverse cardiac remodeling in mice with transverse aortic constriction-induced HF. Furthermore, proteomics revealed that DDX5 is involved in RNA splicing in cardiomyocytes. We found that DDX5 regulated the aberrant splicing of Ca 2+ /calmodulin-dependent protein kinase IIδ ( CamkIIδ ), thus preventing the production of CaMKIIδA, which phosphorylates L-type calcium channel by serine residues of Cacna1c, leading to impaired Ca 2+ homeostasis. In line with this, we found increased intracellular Ca 2+ transients and increased sarcoplasmic reticulum Ca 2+ content in DDX5-depleted cardiomyocytes. Using adeno-associated virus serotype 9 knockdown of CaMKIIδA partially rescued the cardiac dysfunction and HF in Ddx5 knockout mice., Conclusions: These findings reveal a role for DDX5 in maintaining calcium homeostasis and cardiac function by regulating alternative splicing in cardiomyocytes, identifying the DDX5 as a potential target for therapeutic intervention in HF., Competing Interests: None.

The removal of tumors at the root of the tongue can be challenging due to anatomic constraints (deep location of the root of the tongue, obstruction by the mandible), leading to poor surgical visibility. Clear visibility of the surgical field is crucial for complete excision to reduce recurrence, hence the need to choose an appropriate surgical approach based on the tumor's location and size. In this report, the authors describe a case where a midline mandibulotomy and temporary midline glossectomy were utilized to expose and resect a tumor at the root of the tongue. This approach allowed for the complete removal of the tumor while preserving the anterior tongue tissue and bilateral lingual arteries. The defect was then reconstructed using an anterolateral thigh flap. The patient showed good postoperative recovery with significant improvement in swallowing and speech functions. The authors emphasize that the surgical treatment of squamous cell carcinoma (SCC) at the root of the tongue should strive to ensure radical tumor removal while preserving surrounding healthy tissues and critical anatomic structures, particularly the lingual arteries, to facilitate better postoperative recovery for patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Intracranial hypertension is considered a common and severe complication of cryptococcal meningitis (CM), contributing to early mortality and neurological sequelae. Timely and effective control of elevated intracranial pressure is crucial for the management of CM. Herein, the authors present a case of ventricular abdominal wall drainage for CM accompanied with acute intracranial hypertension. Notably, the patient has a history of taking immunosuppressants for thoracic and abdominal diffuse lymphangiomatosis. After continuous drainage of cerebrospinal fluid combined with standardized antifungal treatment, the patient recovered well., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: Glottic contraction and closure causes ventilation obstruction and laryngeal mask airway (LMA) leakage during positive pressure ventilation using LMA. This study aimed to assess the effect of placing the anterior end of the endotracheal tube (ET) at the glottis through the LMA ventilation conduit on treating LMA leakage following glottic contraction and closure., Methods: In this prospective, randomized, controlled trial, patients with non-minor surgery using LMA ventilation were randomly allocated to the i-gel group (group L) and the i-gel combined with ET group (group LE). The tip of ET was placed 2 cm under glottis guided by fiberoptic bronchoscope through i-gel ventilation conduit in group LE. The perioperative incidence of i-gel leakage, the changes of systolic blood pressure (SBP) and heart rate (HR) following artificial airway insertion, and adverse events were recorded., Results: Perioperative i-gel leakage was observed in 7 of 48 patients (14.6%) in group L and 1 of 49 patients (2.0%) in group LE. There was significant difference in the incidence of leakage between the 2 groups (P = .031). SBP and HR after ET insertion in group LE increased significantly compared to those in group L (P < .05/5). The values of both SBP and HR after ET insertion did not exceed the basic values in group LE (P > .05/4). There were no significant differences in the incidence and severity of postoperative sore pain and hoarseness, cough during i-gel and ET removal between the 2 groups (P > .05)., Conclusion: Placing the anterior end of ET at the glottis reduced LMA air leakage related to glottic contraction and closure in non-minor surgery. The ET placing had low stress response and did not significantly increase postoperative complications., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The study was designed to explore the effect of proprioceptive training in contrast to conventional training among individuals following anterior cruciate ligament reconstruction (ACLR). It includes joint position sense (JPS), subjective functional outcomes (Cincinnati, Knee injury Osteoarthritis Outcome Score, International Knee Documentation Committee knee form), muscle strength, pain, and kinesthesia., Methods: PubMed, EMBASE, The Cochrane Library, and Web of Science databases were searched. Quality assessment was performed through the Cochrane Risk of Bias tool and GRADE system. The standardized mean deviation (SMD) was selected as the effect size., Results: Fifteen studies and 537 participants were included. Compared with conventional training, proprioceptive training may significantly enhance passive JPS (SMD = -1.87 [95%CI: -2.39 to -1.34]) and single-leg hop function test performance (SMD = 0.29 [95%CI 0.04 to 0.54]). Data also indicated that proprioceptive training can moderately improve subjective functional outcomes (SMD = 0.61 [95%CI, 0.23 to 0.99]). However, there were no significant effects on active JPS, muscle strength and VAS., Conclusion: Proprioceptive training has the potential to yield beneficial effects on knee passive JPS, hop functional test and subjective functional outcomes in patients after ACLR. However, its impact on enhancing knee active JPS and kinesthesia may not be statistically significant., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to evaluate the impact of dry eye disease (DED) on depression, anxiety, and stress among Chinese doctoral students studying abroad. This is a cross-sectional study. This study enrolled 185 Chinese doctoral students pursuing education in the Philippines. DED was assessed using the Ocular Surface Disease Index, while psychological symptoms were evaluated using the abbreviated version of the Depression, Anxiety, and Stress Scale-21 questionnaire. A survey encompassing demographic information, potential DED risk factors, and individual habits was also administered. Of the 185 students, 129 completed the survey, of which 40 (31.0%) were male and 89 (69.0%) were female. The average age was 36.3 ± 7.0 (mean ± SD; range, 22-57) years. The prevalence of DED, depression, anxiety, and stress was 73.6% (95/129), 43.4% (56/129), 50.4% (65/129), and 22.5% (29/129), respectively. Univariate analysis revealed that aging (P < .001), prolonged visual display terminal (VDT) use (P = .004), extended paperwork time (P < .001), higher depression score (P = .006), higher anxiety score (P < .001), and higher stress score (P < .001) were associated with increased influence of DED. After adjusting for age, duration of VDT use, duration of paperwork, and depression score, age (P = .030) had significant association with DED. Additionally, after adjusting for age, duration of VDT use, duration of paperwork, and anxiety score, age (P = .026) and anxiety score (P = .047) were significantly associated with DED. Moreover, after adjusting for age, duration of VDT use, duration of paperwork, and stress score, age (P = .035) and stress score (P = .028) showed significant associations with DED. In the multivariate analysis of variance, there was a significant impact of DED severity classification on psychological distress (V = 0.19, F(9, 375) = 2.83, P = .003). Univariate analysis of variances indicated that DED severity had a significant impact on anxiety F(3, 125) = 6.06, P = .001 and stress F(3, 125) = 3.00, P = .033. A higher influence of DED was related to stress and anxiety. Anxiety and stress levels increase with the severity of DED., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)