Search

Objective: To analyze duties, tasks, and task elements of health workers in charge of vaccination at public health centers in South Korea. Design: Descriptive study using a survey. Sample: Health workers in charge of vaccination for more than 1 year at 254 public health centers in South Korea. Of 631 health workers, 401 responded to the questionnaire, and 379 responses were included in the analysis after excluding 22 incomplete responses. Measurements: The Developing A Curriculum (DACUM) workshop was conducted to identify the frequency, importance, and difficulty of duties, tasks, and task elements. Results: Four duties (vaccination promotion, vaccination administration and symptom management, execution of vaccination, and vaccination education), 18 tasks, and 81 task elements were identified. "Execution of vaccination" exhibited the highest determinant coefficient. "Implementing the budget" exhibited the highest determinant coefficient among tasks, and "dealing with an emergency in the case of adverse events" exhibited the highest determinant coefficient among task elements. Conclusions: Duty, task, and task elements with high determinant coefficients have high educational needs. Education demands was higher for administrative work than for direct vaccination. Developing an educational curriculum based on DACUM results could contribute to the professional education of vaccine workers. [ABSTRACT FROM AUTHOR]

Background Plasma circular (circ)RNAs detected by droplet digital polymerase chain reaction (ddPCR) may be ideal markers for liquid biopsy. However, ddPCR detection of circRNAs in plasma for diagnosis of lung adenocarcinoma has been rarely reported. Methods An RNA sequencing analysis was performed in plasma from patients with early lung adenocarcinoma and healthy individuals. Droplet digital PCR was used to verify the differentially expressed genes. Results The copy numbers of circle RNA LZIC (circ LZIC)and circle RNA CEP350 (circ CEP350) in the plasma of lung adenocarcinoma patients were significantly higher than in plasma of healthy people, and the copy numbers in postoperative plasma of the same patients were significantly lower than those in preoperative plasma. Circ LZIC and circ CEP350 alone and in combination had diagnostic value in lung adenocarcinoma and early lung adenocarcinoma. Circ LZIC and circ CEP350 had more binding sites with multiple microRNAs. Their target genes were enriched in several signaling pathways. Conclusion The copy numbers of circ LZIC and circ CEP350 were higher in plasma of lung adenocarcinoma patients than in plasma of healthy controls, significantly correlated with tumor size and TNM stage, and closely related to the occurrence and development of tumors. These circRNAs may serve as molecular markers for the diagnosis of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus-associated lymphoproliferative disorders (EBV-LPDs) are a group of disorders involving lymphoid tissues or lymphocytes. The epidemiology and economic burden of hospitalized children with EBV-LPDs in China have not been well studied. This study aimed to reveal the epidemic characteristics and disease burden of EBV-LPDs among the Chinese hospitalized children, providing strategies for the prevention and management. Methods: This study was based on the FUTang Updating medical REcords (FUTURE) database of China and collected the medical records from 27 tertiary children's hospitals between January 2016 and December 2021 in China, counting five types of EBV-LPDs, namely EBV-positive T-cell lymphoproliferative disease, NK/T cell lymphoma, extranodal NK/T-cell lymphoma (nasal type), systemic EBV-positive T-cell lymphoproliferative disease of childhood and posttransplant lymphoproliferative disorders. We conducted a retrospective syhthesis and analysis of the epidemiological characteristics, expenses, length of stay (LOS), as well as complications among hospitalized children diagnosed with five types of EBV-LPDs and compared parameters using appropriate statistical tests. Results: The study described 153 children aged 0–18 years hospitalized with EBV-LPDs from 2016 to 2021 in the FUTURE database. The male-to-female ratio was 1.10:1, and more than half of the age distribution was in the 6–12 y group. Among EBV-LPDs cases, EBV+ T-LPD accounted for the largest proportion (65.36%). Complications were presented in 93 children with EBV-LPDs, mainly hemophagocytic lymphohistiocytosis (HLH). The median LOS of NKTL was 26.5 days [interquartile range (IQR) = 3–42], which was the longest among EBV-LPDs. The median hospitalization cost of PTLD was 10 785.74 United States dollars (IQR = 7 329.38–16 531.18), which was the heaviest among EBV-LPDs. Conclusions: Compared with the total number of hospitalized children in China during the same period and in the same age group, the proportion of EBV-LPD is very low. EBV-LPD can develop in all age groups, but it is more common in school-age children. Among 5 EBV-LPDs, the disease with the highest proportion is EBV+ T-LPD. The overall disease burden of EBV-LPD was heavy, especially the economic burden. HLH was one of the most common complications, which could directly affect the burden of patients because of prolonged hospitalization. These data are taken from a very large database, illustrating the epidemiological and economic burden of EBV-LPDs hospitalized children in China, which enriched the existing epidemiological and disease burden content of EBV-LPDs. [ABSTRACT FROM AUTHOR]

Delpazolid (LCB01‐0371) is a novel oxazolidinone derivative with a good safety profile for treating gram‐positive pathogenic infections such as Mycobacterium abscessus, a highly pathogenic drug‐resistant Mycobacterium. In this study, we evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of delpazolid after 14 days of multiple oral administration, using data from adult patients with pulmonary tuberculosis. 800 mg once a day, 400 mg twice a day, 800 mg twice a day, and 1200 mg once a day delpazolid for 14 days were tested in 63 patients with pulmonary tuberculosis. For PK blood collection, inpatient and outpatient scheduling were separately implemented. Plasma concentrations of delpazolid were measured at visits 2, 4, 6, and 8 in outpatients, and four sparse blood samples were measured in inpatients. PD models were sequentially fitted using individual PK parameter estimates obtained from PK compartmental models. For PK modeling, 180 plasma concentrations of delpazolid from 56 patients were included. A two‐compartment mixed first‐ and zero‐order absorption model best described the time course of plasma concentration. For the PD model, 448 bacterial titer data from 60 patients were used. The time course of bacterial titers (log10 CFU/mL) was described by a model that consists of the growth and killing rate of bacteria with the sigmoid Emax model. The PK–PD simulation suggested that the bacterial titers are the lowest on the 800 mg bid regimen among the four, consistent with observed data, as all regimens substantially decrease. In the dose–response relationship, the effectiveness of delpazolid was suggested. [ABSTRACT FROM AUTHOR]

Background Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. Methods The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life–Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. Results Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7–86.7) and 81.5 (70.4–92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91–0.96) and respiratory symptoms (0.92; 0.89–0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28–1.39) or respiratory symptoms (1.30; 0.62–2.74). Conclusions After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. Clinical Trials Registration ClinicalTrials.gov identifier: NCT03934034. [ABSTRACT FROM AUTHOR]

Hyperuricemia exhibits a high incidence among individuals with diabetes; however, the significance of hyperuricemia and gout is often underestimated. This study aimed to assess the knowledge, attitude, and practice of hyperuricemia and gout among community health workers and patients with diabetes. Two questionnaires were designed to investigate knowledge, attitudes, and practices of hyperuricemia and gout among community health workers and patients with diabetes in Chenghua District, Chengdu, from August 2021 to January 2022. A total of 709 community health workers were included, whose average score was 17.74/30. Approximately half of general practitioners (GPs) demonstrated knowledge regarding the target serum uric acid levels for hyperuricemia and gout. Only 11.2% of GPs were fully aware of the preferred medicine for acute gout. The majority of GPs (86.7%) demonstrated limited awareness regarding the contraindications associated with colchicine, while a significant proportion (65.1%) lacked knowledge about the specific classes of drugs that inhibit uric acid synthesis. Among the 508 patients with diabetes included in this survey, 32.3% demonstrated awareness of hyperuricemia, while 60.8% exhibited knowledge regarding gout. The average score attained by these individuals was recorded at 7.21 out of a total of 26 points. The majority of patients with diabetes (87.8%) held the mistaken belief that hyperuricemia definitely led to the development of gout. Almost 66% agreed that a massage or a hot compress could be used when acute gouty arthritis attacks. The knowledge rate of hyperuricemia and gout among community health workers was moderate, while it was low in patients with diabetes. [ABSTRACT FROM AUTHOR]

Background and Purpose: Compassion is increasingly considered essential to quality nursing care and is a concept that is strongly embedded across cultures, including Chinese culture. The Patient Compassion Model (PCM) depicts the unique yet overlapping domains of compassion. The Sinclair Compassion Questionnaire (SCQ) was directly developed and validated from this empirical model. In this study, we sought to establish initial validation of a translated SCQ among Mandarin-speaking patients by assessing the transferability of the PCM and the clinical sensibility of the SCQ. Methods: Forward and back-translation of the PCM and SCQ were performed in accordance with World Health Organization guidelines. Qualitative interviews were used to assess the transferability of the PCM with conceptualizations of compassion within a Chinese context. Cognitive interviews were conducted to assess the clarity, readability, wording, questions, and response scales of the Mandarin translation of the SCQ. Qualitative data were analyzed using constant comparative analysis, and cognitive interviews were analyzed using framework analysis. Results: The original categories of the PCM were verified in this Mandarin-speaking patient population. Specifically, participants' understanding of compassion is described as consisting of healthcare provider virtues, emphasizing the importance of a virtuous response that sought to understand the individual and their unique needs, to relationally communicate from a place of shared humanity and to ameliorate suffering. Participants were able to answer, comprehend, and endorse all 15 Mandarin SCQ items, resulting in no modifications to the Mandarin SCQ. Conclusions: This study provides initial validation of the Mandarin SCQ and PCM. Future studies should consider further establishing the validity and reliability of the Mandarin SCQ among a larger Chinese patient population. [ABSTRACT FROM AUTHOR]

Hoarding behavior is prevalent in children and adolescents, yet clinicians do not routinely inquire about it and youth may not spontaneously report it due to stigma. It is unknown whether hoarding behavior, over and above obsessive-compulsive symptoms (OCS), is associated with major clinical factors in a general youth population. This observational study included N = 7054 youth who were not seeking help for mental health problems (ages 11–21, 54% female) and completed a structured interview that included evaluation of hoarding behavior and OCS, as a part of the Philadelphia Neurodevelopmental Cohort between November 2009 and December 2011. We employed regression models with hoarding behavior and OCS (any/none) as independent variables, and continuous (linear regression) or binary (logistic regression) mental health measures as dependent variables. All models covaried for age, sex, race, and socioeconomic status. A total of 374 participants endorsed HB (5.3%), most of which reported additional OCS (n = 317). When accounting for OCS presence, hoarding behavior was associated with greater dimensional psychopathology burden (i.e., higher P-factor) (β = 0.19, p <.001), and with poorer functioning (i.e., lower score on the child global assessment scale) (β = − 0.07, p <.001). The results were consistent when modeling psychopathology using binary variables. The results remained significant in sensitivity analyses accounting for count of endorsed OCS and excluding participants who met criteria for obsessive-compulsive disorder (n = 210). These results suggest that hoarding behavior among youth is associated with poorer mental health and functioning, independent of OCS. Brief hoarding-behavior assessments in clinical settings may prove useful given hoarding behavior's stigma and detrimental health associations. [ABSTRACT FROM AUTHOR]

Background: Inequities in access to human papillomavirus (HPV) vaccine are becoming a growing critical issue globally. Few studies investigate the factors determining HPV vaccine uptake disparities when vaccine supply is constrained, especially in low- and middle-income countries. The aim of this study was to investigate inequities of HPV vaccination and related factors under the constrained vaccine supply in China. Methods: A cross-sectional survey was conducted in a developed eastern coastal province and a developing western one in China between November and December 2022. Employing multistage stratified cluster random sampling, the study collected data from parents of children aged 9–14. Mixed-effects logistic regression models with school units as random effects were used for analysis. Results: From 4,127 eligible parents (as vaccine decision makers for girls), 1,346 (32.6%) intended to vaccinate their daughters against HPV, of which 836 (62.1%) attempted to schedule a vaccination appointment. Only 16.4% succeeded in booking an appointment. More than half of the intended parents expected the imported 9-valent HPV vaccine. There were significant disparities in HPV vaccine awareness, intention, and vaccination behavior across educational, income, geographic, ethnic, gender, and health literacy levels. Vaccine awareness and intentions were higher among parents with higher socioeconomic status; however, girls from lower socioeconomic families were more likely to receive the HPV vaccine and had a higher domestically produced vaccination rate. Significant disparities exist in vaccination intentions and actual vaccination behaviors, primarily due to large supply constraints of the HPV vaccine. Conclusions: Sustained health education campaigns are needed to raise awareness of the HPV vaccine, improve health literacy, and decrease over-preference for the 9-valent HPV vaccine. A mother's HPV vaccination behavior was positively associated with increased intention and actual vaccination behavior for her daughter. This study advocates for complementary cervical cancer prevention programs targeting both mothers and daughters. [ABSTRACT FROM AUTHOR]

Simple Summary: We developed an attention-based whole slide image (WSI)-level classification deep learning model employing surgically and endoscopically resected specimens to predict LNM in T1 CRC. Our AI model with H&E-stained WSIs and without annotations showed good performance power with the validation of an independent cohort in a single center. The area under the curve of our model was 0.781–0.824, higher than that of previous artificial intelligence (AI) studies with only WSIs. Our AI model, which showed the highest sensitivity (92.9%), reduced unnecessary additional surgery by 14.2% more than using the current JSCCR guidelines (68.3% vs. 82.5%). This revealed the feasibility of using an AI model with only H&E-stained WSIs to predict LNM in T1 CRC. According to the current guidelines, additional surgery is performed for endoscopically resected specimens of early colorectal cancer (CRC) with a high risk of lymph node metastasis (LNM). However, the rate of LNM is 2.1–25.0% in cases treated endoscopically followed by surgery, indicating a high rate of unnecessary surgeries. Therefore, this study aimed to develop an artificial intelligence (AI) model using H&E-stained whole slide images (WSIs) without handcrafted features employing surgically and endoscopically resected specimens to predict LNM in T1 CRC. To validate with an independent cohort, we developed a model with four versions comprising various combinations of training and test sets using H&E-stained WSIs from endoscopically (400 patients) and surgically resected specimens (881 patients): Version 1, Train and Test: surgical specimens; Version 2, Train and Test: endoscopic and surgically resected specimens; Version 3, Train: endoscopic and surgical specimens and Test: surgical specimens; Version 4, Train: endoscopic and surgical specimens and Test: endoscopic specimens. The area under the curve (AUC) of the receiver operating characteristic curve was used to determine the accuracy of the AI model for predicting LNM with a 5-fold cross-validation in the training set. Our AI model with H&E-stained WSIs and without annotations showed good performance power with the validation of an independent cohort in a single center. The AUC of our model was 0.758–0.830 in the training set and 0.781–0.824 in the test set, higher than that of previous AI studies with only WSI. Moreover, the AI model with Version 4, which showed the highest sensitivity (92.9%), reduced unnecessary additional surgery by 14.2% more than using the current guidelines (68.3% vs. 82.5%). This revealed the feasibility of using an AI model with only H&E-stained WSIs to predict LNM in T1 CRC. [ABSTRACT FROM AUTHOR]

Conventional treatments for allergic rhinitis (AR) exhibit insufficiency and long-term use-related side effects. Considering the reported anti-inflammatory and immunoregulatory effects of Bojungikgi-tang (BJIGT), we aimed to assess its efficacy on persistent AR (PAR). Patients with PAR were randomly assigned in a 1:1:1 ratio into high-dose BJIGT, standard-dose BJIGT, and placebo groups, followed by 1-week run-in and 4-week treatment periods. The primary outcome included the mean change in Total Nasal Symptom Score (TNSS), with secondary outcomes encompassing the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, biomarkers, overall assessment, TNSS by AR pattern identification, and the Sasang constitution. The mean TNSS change was more improved in the BJIGT group than in the placebo group; however, no statistically significant differences were observed. Additional interaction effect analysis revealed a statistically significant improvement in the high-dose BJIGT group compared with the placebo group from weeks 1–2 to weeks 3–4. Regarding secondary outcomes, the BJIGT group exhibited similar or improved results compared with the placebo group, showing no statistically significant differences. No serious adverse effects or clinically significant changes in safety assessments were observed. Given that this study validated clinical improvement and safety, it serves as potential groundwork for pertinent future studies. [ABSTRACT FROM AUTHOR]

Background: Teeth identification has a pivotal role in the dental curriculum and provides one of the important foundations of clinical practice. Accurately identifying teeth is a vital aspect of dental education and clinical practice, but can be challenging due to the anatomical similarities between categories. In this study, we aim to explore the possibility of using a deep learning model to classify isolated tooth by a set of photographs. Methods: A collection of 5,100 photographs from 850 isolated human tooth specimens were assembled to serve as the dataset for this study. Each tooth was carefully labeled during the data collection phase through direct observation. We developed a deep learning model that incorporates the state-of-the-art feature extractor and attention mechanism to classify each tooth based on a set of 6 photographs captured from multiple angles. To increase the validity of model evaluation, a voting-based strategy was applied to refine the test set to generate a more reliable label, and the model was evaluated under different types of classification granularities. Results: This deep learning model achieved top-3 accuracies of over 90% in all classification types, with an average AUC of 0.95. The Cohen's Kappa demonstrated good agreement between model prediction and the test set. Conclusions: This deep learning model can achieve performance comparable to that of human experts and has the potential to become a valuable tool for dental education and various applications in accurately identifying isolated tooth. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status. Methods: Data were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors. Results: Over a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19–1.58) for all-cause mortality and 1.63 (95% CI, 1.29–2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03–1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08–2.04) remained statistically significant (both p-values for trend < 0.05) in prediabetes subjects. The 10-year cumulative survival probability was determined to be 70.34%, 84.65% for all-cause events, and 86.21%, 94.54% for cardiovascular events in top NLR tertile of diabetes and prediabetes individuals, respectively. Furthermore, each incremental unit in the absolute value of NLR was associated with a 16%, 12% increase in all-cause mortality and a 25%, 24% increase in cardiovascular mortality among diabetes and prediabetes individuals, respectively. Conclusions: The findings of this prospective cohort study conducted in the US indicate a positive association of elevated NLR levels with heightened risks of overall and cardiovascular mortality among adults with diabetes and prediabetes. However, potential confounding factors for NLR and the challenge of monitoring NLR's fluctuations over time should be further focused. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the systematic review is to verify the presence of PANoptosis in periodontitis based on the published literatures studying cell death in periodontitis. Materials and Methods: We conducted a comprehensive review of literature studying the types of cell death in vitro cellular experiments, in vivo rodent studies and clinical studies from three major databases: PubMed, Scopus, and Web of Science. The present systematic review was recorded in the PROSPERO database, under registration number CRD42022383456. Results: In total, 51 articles were included in this study. Our analysis of in vitro cell models revealed that pyroptosis, necroptosis, and apoptosis could be induced by periodontal pathogens in macrophages, fibroblasts, stem cells, and periodontal ligament cells. Furthermore, three types of cell death were detected in in vivo rodent periodontitis models. Clinical studies on human periodontitis tissue specimens and gingival crevicular fluid (GCF) showed that some key proteins related to pyroptosis, necroptosis, and apoptosis were elevated in periodontitis. Conclusions: Various studies have established similar in vivo and in vitro models with three modes of death detected under the same conditions, revealing complex interactions between different types of cell death pathways in periodontitis and the potential for PANoptosis to occur in periodontitis. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic gingival fibromatosis (IGF) is a rare heterogeneous disease that results in the progressive and diffuse hyperplasia of gingival tissues. MicroRNAs are implicated in the development and progression of various tumors. The present study aimed to explore the potential roles and mechanisms of miR‐148a‐3p in IGF. Methods: Gingival fibroblasts (GFs) were transfected with miR‐148a‐3p mimics, miR‐148a‐3p inhibitors, or siNPTX1, and then, the proliferation and apoptosis of GFs and the expression of related genes were evaluated using Cell Counting Kit‐8 assays, 5‐ethynyl‐2′‐deoxyuridine assays, flow cytometry, reverse transcription‐quantitative polymerase chain reaction, and western blot analysis, respectively. Results: miR‐148a‐3p was highly expressed in GFs of IGF (IGF‐GFs) as compared with normal GFs (N‐GFs). Overexpression of miR‐148a‐3p promoted the proliferation and inhibited the apoptosis of N‐GFs, whereas downregulation of miR‐148a‐3p had the opposite effect in IGF‐GFs. Knockdown of NPTX1 reversed miR‐148a‐3p‐mediated effects in IGF‐GFs. Dual‐luciferase reporter assay confirmed that NPTX1 is a direct target of miR‐148a‐3p. Conclusion: These findings identify that miR‐148a‐3p could regulate cell proliferation and apoptosis by targeting NPTX1, providing new insights for the further study of the molecular mechanism and treatment of IGF. [ABSTRACT FROM AUTHOR]

HIV-related stigma is a major challenge to HIV prevention for sexual minority men (SMM) in Zambia, but little is known about the underlying mechanisms. This study aimed to investigate whether physician–patient interaction quality mediates the relationship between HIV-related stigma and HIV-prevention behaviors among SMM. Data were collected using a cross-sectional survey from 194 SMM (aged: mean = 24.08, SD = 4.27) across four districts in Zambia between February and November 2021. Participants were asked about their demographic characteristics, HIV-related stigma, SMM-related stigma, physician–patient interaction quality, HIV-testing intention, and use of pre-exposure prophylaxis (PrEP). Path analysis was used to test the mediation effect of physician–patient interaction quality in the associations of HIV-related stigma/SMM-related stigma with HIV-testing intention and current PrEP use. Higher self-reported physician–patient interaction quality was negatively associated with HIV-related stigma (β = − 0.444, z = − 2.223, p < 0.05), and positively associated with HIV-testing intention (β = 0.039, z = 5.121, p < 0.001) and current PrEP use (β = 0.008, z = 2.723, p < 0.01). HIV-related stigma among SMM had a significant and negative indirect effect on HIV-testing intention (β = − 0.017, z = − 2.006, p < 0.05), and current PrEP use (β = − 0.004, z = − 2.009, p < 0.05) through physician–patient interaction quality. Contrary to our expectations, SMM-related stigma did not have a significant and negative indirect effect on HIV prevention behaviors through physician–patient interaction quality. Health interventions need to improve physician–patient interaction quality by offering healthcare provider training, targeting HIV-related stigma in healthcare settings, and devising inclusive healthcare policies to promote HIV prevention efforts. [ABSTRACT FROM AUTHOR]

Background: New nurses are prone to workplace deviant behavior in the constrained hospital environment, which will not only directly affect the safety of patients, but also reduce the work efficiency of nurses and bring negative results to the hospital. The purpose of this study was to investigate the relationship between perceived organizational justice, emotional labor, psychological capital, and workplace deviant behavior of new nurses. Methods: A cross-sectional study was used in this study. A survey was conducted in 5 hospitals in Henan Province, Chain from February to April 2023. The sample size was 546. The questionnaire included general information, perceived organizational justice scale, emotional labor scale, psychological capital scale, and workplace deviant behavior scale. SPSS 26.0 and PROCESS Macro were used for data analysis. PROCESS Model 4 and Model 14 were used to verify the model. Results: This study displays that perceived organizational justice was negatively correlated with emotional labor and workplace deviant behavior, and emotional labor was positively correlated with workplace deviant behavior. Meanwhile, emotional labor plays a partial mediating role between perceived organizational justice and workplace deviant behavior, accounting for 32.7% of the total effect. Moreover, the path of emotional labor on workplace deviant behavior is moderated by psychological capital. Conclusion: This study further understood the workplace deviant behavior of new nurses, and provided a new perspective for solving this problem. Nurse managers can reduce workplace deviant behavior by enhancing the perceived organizational justice and psychological capital of new nurses and improving emotional labor. [ABSTRACT FROM AUTHOR]

Background: The impact of long-term Coronavirus disease 2019 (COVID-19) on the pediatric population is still not well understood. This study was designed to estimate the magnitude of COVID-19 long-term morbidity 3–6 months after the date of diagnosis. Methods: A retrospective study of all Clalit Health Services members in Israel aged 1–16 years who tested positive for SARS-CoV-2 between April 1, 2020 and March 31, 2021. Controls, who had no previous diagnosis of COVID-19, were one-to-one matched to 65,548 COVID-19-positive children and teens, and were assigned the infection dates of their matches as their index date. Matching included age, sex, socio-economic score, and societal sector. Individuals were excluded from the study if they had severe medical conditions before the diagnosis such as cancer, diabetes, chronic respiratory diseases, and/or abnormal physiological development. Generalized Estimating Equations were used to estimate the associations between COVID-19 and the use of medical services. The analysis focused on the 3–6 months after the infection date. Adjustments were made for demographics and for the use of medical services 6–12 and 3–6 months before the infection date. The latter was necessary because of observed disparities in medical service utilization between the groups before the COVID-19 diagnosis, despite the matching process. Results: Statistically significant differences were only found for referrals for mental health services [adjusted relative-risk (RR) 1·51, 95%CI 1·15 − 1·96; adjusted risk-difference (RD) 0·001, 95%CI 0·0006 − 0·002], and medication prescriptions of any kind (RR 1·03, 95%CI 1·01–1·06; RD 0·01 95%CI 0·004 − 0·02). Conclusions: The significant increase in medication prescriptions and mental health service referrals support the hypothesis that COVID-19 is associated with long-lasting morbidities in children and adolescents aged 1–16 years. However, the risk difference in both instances was small, suggesting a minor impact on medical services. [ABSTRACT FROM AUTHOR]

A plethora of scientific evidence has pinpointed that teaching English as a foreign or second language (EFL) is difficult, challenging, and emotionally burdensome. Nevertheless, most English language teachers remain committed to the teaching profession and actively engage in the instructional environment. This has inspired several scholars worldwide to explore what personal, emotional, and psychological factors motivate English language teachers to engage enthusiastically in their workplace. While a large body of studies have to date examined the personal, emotional, and psychological predictors of English language teachers' work engagement, to our knowledge, no inquiry has investigated the role of academic buoyancy and self-efficacy in predicting EFL teachers' work engagement. Furthermore, the potential impact of demographic variables on the interplay between EFL teachers' academic buoyancy, self-efficacy, and work engagement has been disregarded. To bridge this gap, we examined the interplay of these three constructs among Chinese EFL teachers. To do so, we administered three pre-designed questionnaires to 242 EFL teachers working in Chinese schools and universities. The collected data were then analyzed using structural equation modeling (SEM). The outcomes of SEM divulged positive and strong relationships between Chinese EFL teachers' academic buoyancy, self-efficacy, and work engagement. The SEM results also indicated that academic buoyancy and self-efficacy could strongly and favorably predict Chinese EFL teachers' work engagement. Additionally, the study outcomes disclosed that demographic variables, including gender, educational degree, and teaching experience, directly impacted the interplay between Chinese EFL teachers' academic buoyancy, self-efficacy, and work engagement. These results may have significant implications for English teachers, teacher trainers, and educational principals. [ABSTRACT FROM AUTHOR]

Background: Students who are blind are integrated into public schools in many countries, yet are often excluded from full participation in science since most learning materials are visual. To create a compensatory route, an existing model‐based inquiry‐learning environment was adapted by means of sonification (addition of non‐speech sounds that represent dynamic information). The learning environment uses agent‐based models and a complex systems approach to teach the Kinetic Molecular Theory (KMT) and Gas Laws. The models are accompanied by a workbook consisting of text (printed or auditory) and images (printed or tactile). Objectives: The current research examined whether such perceptual compensation creates a comparable learning environment for learners who are blind compared with learners who are sighted using the original learning environment. The aim of the study is to expand knowledge about how the auditory channel may compensate the visual channel among individuals who are blind. Methods: Conceptual learning in science and reasoning about complex systems were assessed using pre‐ and post‐questionnaires. To explore learners' learning progression throughout the unit, four progression analysis 'windows' were selected. These were groups of adjacent or nearly adjacent items in the workbook that permitted a glimpse of learners' progression. Results: The sonified environment not only supported the learning of learners who are blind compared with the learning of learners who are sighted using visual material, but even furthered their learning with respect to diffusion, one of the more challenging concepts in KMT. It seems the types of sonified representations used in this study increased listeners' sensitivity to the micro‐level interactions in a way less accessible in visual representations. Takeaways: Sonified environments can be provide learners who are blind with equitable participation by compensating and complementing the visual channel. Sonification can have implications for students who are blind as well as students who are sighted. Lay Description: What is already known: Sonification is the use of non‐speech sounds to represent dynamic information. Sonification can potentialy be used to allow equitable participation for students who are blind. What this paper adds: To test this, the study compared the outcomes of learners who are blind who used a sonified learning environment (L2C) to that of learners who are sighted who used a visual environment. Implications for practice: Learners who are blind showed equal or better learning outcomes using the sonified models compared with the learners who are sighted using the visual models. There are major implications for integrating students who are blind in public school classrooms. [ABSTRACT FROM AUTHOR]

Background: The relationship between different surgical treatments and quality of life remains uncertain for differentiated thyroid carcinoma (DTC). The aim of this study is to compare the gasless endoscopic thyroidectomy trans-axillary approach (ET) and traditional open thyroidectomy (OT) through a prospective cohort study focusing on the rate of the efficacy, and quality of life (QoL). Methods: This prospective observational longitudinal cohort study enrolled 134 female patients diagnosed with DTC from December 01/2021 to December 31/2022. Multiple scales were applicated to evaluate the differences in quality of life, effectiveness, safety, etc. between the two groups during preoperative and postoperative follow-up periods, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 3.0 (QOL-C30), Symptom Checklist (SCL-90), Scar Cosmesis Assessment and Rating (SCAR-Q), voice impairment score (VIS), swallowing impairment score (SIS), and neck impairment score (NIS). Results: Among them, 68 accepted ET and 66 patients underwent OT. To enhance comparability between the two groups, the patients enrolled in this study are female. Compared with the OT group, the ET group performed significantly better postoperative physical quality of life, including sound (p = 0.036), swallowing (p < 0.001), and neck function (p = 0.010). The ET group was also associated with significantly better cosmetic satisfaction (p < 0.001), and relatively faster recovery in psychological and emotional situation. Conclusions: Gasless endoscopic thyroidectomy through an axillary approach leads to good cosmetic and psychological effects, improves postoperative QoL, and could be recommended for rapid postoperative recovery and involvement in daily and social activities. [ABSTRACT FROM AUTHOR]

Background: The clinical staging of non‐small cell lung cancer (NSCLC) is well known to be related to their prognosis. However, there is usually a discrepancy between clinical staging and pathological staging. There are few analyses of clinical staging accuracy in patients with NSCLC. We compared the concordance rate between clinical and pathological staging of NSCLC and evaluated factors affecting the accuracy in real‐world data. Methods: Altogether, 811 patients with primary NSCLC who had undergone curative lung resection surgery in Severance Hospital from January 2019 to December 2020 were retrospectively reviewed. We used the eighth edition of the American Joint Committee on Cancer TNM staging. Results: Among 811 patients, endobronchial ultrasound (EBUS) and positron emission tomography (PET‐CT) were performed in 31.6% and 96.7%, respectively. The concordance rates between clinical and pathological TNM staging, T factor, and N factor, were 68.7%, 77.7%, and 85.8%, respectively. With multivariable logistic regression analysis, current smokers (OR 0.49; 95% CI: 0.32–0.76, p = 0.001) and a higher clinical stage (p < 0.001) contributed to the clinical staging inaccuracy. Additionally, the presence of a bronchoscopy specialist was significantly associated with clinical staging accuracy (OR 1.53; 95% CI: 1.10–2.13, p = 0.011). Conclusion: Clinical staging accuracy in NSCLC improved compared to before the widespread use of PET‐CT and EBUS in clinical staging work‐up. Smoking history and absence of expert bronchoscopy specialists showed a meaningful correlation with the inaccuracy of clinical staging. Thus, training more bronchoscopy experts would improve the staging accuracy of NSCLC, which could positively affect the prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

Eschar dermabrasion is an easy, cost‐effective and dependable technique for debriding deep partial‐thickness burn wounds, highly suitable for paediatric scalds. Postoperative dressing plays a crucial role in the subsequent healing process. While allogenic skin (AGS) has long been considered as the optimal coverage for abraded burn wounds by Chinese burn specialists, its clinical application on children has encountered challenges. In recent years, our department has observed promising results in the application of bacterial cellulose dressing on paediatric burn wounds after dermabrasion surgery. This study aimed to retrospectively review qualified cases from the past 5 years and categorize them into two groups: 201 cases in the AGS group and 116 cases in the bacterial cellulose dressing (BCD) group. Upon statistical analysis, no differences were oberved between the groups in terms of demographic information and wound characteristics. However, the BCD group had a significantly longer surgery time (44.3 ± 7.0 min vs. 31.5 ± 6.1 min, p < 0.01) and shorter healing time (19.6 ± 2.2 days vs. 24.4 ± 4.3 days, p < 0.01) compared to the AGS group. Moreover, the BCD group required fewer dressing changes (3.5 ± 0.8 vs. 6.7 ± 2.1, p < 0.01) and demonstrated lower rates of skin grafting (10/116 vs. 46/201, p = 0.036). In conclusion, our findings suggest that the bacterial cellulose material may serve as an optimal coverage option for paediatric abraded scald wounds. [ABSTRACT FROM AUTHOR]

Aims: To establish a cognitive appraisal path model that examines the impact of stroke knowledge on stigma with the parallel mediating effects of negative and positive coping traits, as well as the moderating effects of family functioning. Background: Stroke‐related stigma, a 'mixture' of negative emotions involving internal criticism and external judgement, has been shown to impair patients' health outcomes. However, the specific factors underlying cognitive appraisals and their pathways remain unknown. Design: A cross‐sectional design. Methods: The cross‐sectional sample was from two stroke centres in China. Questionnaires were administered to collect sociodemographic data, stroke knowledge, coping traits, family functioning and stigma. Hierarchical regression models and the moderated parallel mediation model were constructed to analyse influencing pathways. The study adhered to the strengthening the reporting of observational studies in epidemiology guideline. Results: All 144 samples reported stigma symptoms with a moderate‐to‐high standardising score. The best hierarchical regression model explains 55.5% of the variance in stigma. The parallel mediation model indicated that negative and positive coping traits co‐mediating the association of stroke knowledge and stigma. After adding the family functioning as a moderator, the moderated parallel mediation model was confirmed with adequate fit indices. Conclusion: Among the cognitive appraisal factors affecting stroke‐related stigma, stroke knowledge reduces stigma by modifying coping traits, while poor family functioning may serve as an opposing moderator. Notably, when family support is insufficient, enhanced stroke knowledge might paradoxically exacerbate the stigma. Relevance to Clinical Practice: This study contributes knowledge on transforming health education and emphasises the pivotal roles of clinical nursing practitioners. In similar global contexts, the study highlights integrating health education, psychological counselling and family support to advance systematic nursing practices. Patient or Public Contribution: None. [ABSTRACT FROM AUTHOR]

Background: There is substantial evidence to support the use of several methods for preventing deep-vein thrombosis (DVT) following intracerebral hemorrhage (ICH). However, the extent to which these measures are implemented in clinical practice and the factors influencing patients' receipt of preventive measures remain unclear. Therefore, we aimed to evaluate the rate of the early implementation of DVT prophylaxis and the factors associated with its success in patients with ICH. Methods: This study enrolled 49,950 patients with spontaneous ICH from the Chinese Stroke Center Alliance (CSCA) between August 2015 and July 2019. Early DVT prophylaxis implementation was defined as an intervention occurring within 48 h after admission. Univariate and multivariate logistic regression analyses were conducted to identify the rate and factors associated with the implementation of early prophylaxis for DVT in patients with ICH. Results: Among the 49,950 ICH patients, the rate of early DVT prophylaxis implementation was 49.9%, the rate of early mobilization implementation was 29.49%, and that of pharmacological prophylaxis was 2.02%. Factors associated with an increased likelihood of early DVT prophylaxis being administered in the multivariable model included receiving early rehabilitation therapy (odds ratio [OR], 2.531); admission to stroke unit (OR 2.231); admission to intensive care unit (OR 1.975); being located in central (OR 1.879) or eastern regions (OR 1.529); having a history of chronic obstructive pulmonary disease (OR 1.292), ischemic stroke (OR 1.245), coronary heart disease or myocardial infarction (OR 1.2); taking antihypertensive drugs (OR 1.136); and having a higher Glasgow Coma Scale (GCS) score (OR 1.045). Conversely, being male (OR 0.936), being hospitalized in tertiary hospitals (OR 0.778), and having a previous intracranial hemorrhage (OR 0.733) were associated with a lower likelihood of early DVT prophylaxis being administered in patients with ICH. Conclusions: The implementation rate of early DVT prophylaxis among Chinese patients with ICH was subpar, with pharmacological prophylaxis showing the lowest prevalence. Various controllable factors exerted an impact on the implementation of early DVT prophylaxis in this population. [ABSTRACT FROM AUTHOR]

Background: Radiomics is increasingly utilized to distinguish pulmonary nodules between lung adenocarcinoma (LUAD) and tuberculosis (TB). However, it remains unclear whether different segmentation criteria, such as the inclusion or exclusion of the cavity region within nodules, affect the results. Methods: A total of 525 patients from two medical centers were retrospectively enrolled. The radiomics features were extracted according to two regions of interest (ROI) segmentation criteria. Multiple logistic regression models were trained to predict the pathology: (1) The clinical model relied on clinical‐radiological semantic features; (2) The radiomics models (radiomics+ and radiomics−) utilized radiomics features from different ROIs (including or excluding cavities); (3) the composite models (composite+ and composite−) incorporated both above. Results: In the testing set, the radiomics+/− models and the composite+/− models still possessed efficient prediction performance (AUC ≥ 0.94), while the AUC of the clinical model was 0.881. In the validation set, the AUC of the clinical model was only 0.717, while that of the radiomics+/− models and the composite+/− models ranged from 0.801 to 0.825. The prediction performance of all the radiomics+/− and composite+/− models were significantly superior to that of the clinical model (p < 0.05). Whether the ROI segmentation included or excluded the cavity had no significant effect on these models (radiomics+ vs. radiomics−, composite+ model vs. composite−) (p > 0.05). Conclusions: The present study established a machine learning‐based radiomics strategy for differentiating LUAD from TB lesions. The ROI segmentation including or excluding the cavity region may exert no significant effect on the predictive ability. [ABSTRACT FROM AUTHOR]

Background: Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. Methods: This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Results: Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. Conclusion: High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD. [ABSTRACT FROM AUTHOR]

Background: Caregivers are responsible for the home care of family members with severe mental illnesses (SMIs) and their lives are often subject to changes that can create stress and burden. The purpose of this study was to explore the current state of family disease burden and its correlation with social support among family caregivers of SMIs patients. Methods: Using a random sampling method, a total of 1,108 family caregivers of SMIs patients in community health service centers were selected. A general information questionnaire of family caregivers and patients, the Family Disease Burden Scale, and the Social Support Rating Scale were used. Results: The score of the Family Disease Burden Scale of 1108 family caregivers was 16.57 ± 10.65. Family disease burden was negatively correlated with social support (p <.05). The main influencing factors of family disease burden were average annual family income, duration of illness, distance to medical care, risk of unpredictable behavior, social support, caregiver-patient relationship, gender, and comorbid chronic conditions (p <.05). Conclusion: Family caregivers of SMIs patients have a relatively low level of caregiver-perceived social support. Interventions to enhance perceived social support could help maintain the health of family caregivers and improve the quality of family care. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) is a pandemic to which nursing students are particularly susceptible. This study aims to comprehensively examine nursing students' knowledge, attitudes, risk perceptions, preventive behaviors related to COVID-19, and nursing intentions toward patients with the virus. A questionnaire was administered to 149 nursing students from two universities. Data on the respondents' general characteristics, knowledge levels, attitudes, perceived risk, preventive behaviors toward COVID-19, and nursing intentions toward COVID-19 patients were collected. The collected data were statistically analyzed using SPSS software (version 26.0). This involved descriptive statistics, independent t-tests, one-way ANOVA, Pearson's correlation coefficient, and stepwise multiple regression analyses. The analyses of the factors affecting nursing students' nursing intentions for COVID-19 patients showed that the most predictive factor was perceived risk (β = −0.38, p < 0.001), followed by attitudes (β = 0.29, p < 0.001) and preventive behaviors (β = 0.17, p = 0.017), which explained 26% of the variance in nursing intentions. Lowering the perceived risk of infectious diseases and cultivating positive attitudes and preventive behaviors can increase nursing students' intentions toward COVID-19 patients. Finally, infection management education programs and research on interventions for nursing students are necessary to enhance the quality of nursing care provided to patients with novel infectious diseases. [ABSTRACT FROM AUTHOR]

It is difficult to avoid deep surgical site infection after spinal surgery. Debridement combined with closed suction irrigation (CSI) and other treatment methods lead to greater trauma and lower satisfaction. We developed a new method for the treatment of SSI, which has the advantages of less invasiveness and lower cost. The cohort of this retrospective study comprised 26 patients with SSI after undergoing spinal surgery in our hospital from August 2017 to March 2022. The patients were divided into CSI and microtube drainage group according to treatment methods. The durations of antibiotic use and hospital stay, hospitalization costs, and functional scores during follow‐up were compared between the two groups. The only baseline characteristic that differed between the two groups was sex. Infection was controlled in both groups and there were no recurrences during follow‐up. However, the length of hospital stay after the first operation and the total length of stay were significantly greater in the CSI group. Hospitalization costs and antibiotic costs were significantly higher in the CSI group. Additionally, the duration of intravenous antibiotic use was significantly longer in the CSI group. Both the CSI and microtube drainage groups had significantly improved of Short Form Health Survey (SF‐36) scores 6 months postoperatively. However, 3 months postoperatively, SF‐36 scores were significantly lower in the CSI group. Compared with debridement followed by CSI, percutaneous micro‐drainage tube irrigation combined with high negative pressure tube drainage is a more efficient and economical means of treating SSI after spinal surgery. [ABSTRACT FROM AUTHOR]

Few studies have been conducted to explore medication non-adherence in persons with schizophrenia (PWS) and its influencing factors in rural China. This study aimed to investigate the medication non-adherence and its influencing factors among PWS in rural China. A total of 269 PWS and their family caregivers in Xinjin district, Chengdu, China were investigated on medication adherence and related factors. Logistic regression was employed to identify the influencing factors. The results showed that 37.6% of PWS had medication non-adherence. PWS living with family caregivers had significantly lower rate of medication non-adherence (34.7%) than those not living with family caregivers (60.0%) (p < 0.01). Family caregivers' affiliate stigma of mental illness, knowledge of mental illness and self-esteem were significantly related to patients' medication non-adherence (p < 0.05). PWS' employment status, living with family caregiver, present mental status and social support were significantly related to medication adherence. This study shows medication non-adherence is severe among PWS in rural China. Both patient- and family-related factors affect patients' medication adherence seriously. Except improving patients' treatment and mental status, development of family caregiving, social support network and intervention on reducing stigma of mental illness should be crucial for enhancing PWS' medication adherence. [ABSTRACT FROM AUTHOR]

Depression is one of the most common mental health problems among people living with HIV (PLWH). However, the longitudinal psychological mechanism underlying the link of internalized HIV stigma and depressive symptoms remains a research gap. This study attempted to articulate how and to what extent perceived social support and resilience mediate the longitudinal associations between internalized HIV stigma and depressive symptoms. A sample consisting of 1,098 Chinese PLWH (Mage = 38.63, SD = 9.20; 63.9% male) with a six-month interval and four waves of follow-up was used in the current study. Participants were asked to complete self-report questionnaires. The associations among main study variables were examined via a complete longitudinal mediation approach. Results indicated that the linkage between internalized HIV stigma at T1 and depressive symptoms at T4 was serially mediated by perceived social support at T2 and resilience at T3, and perceived social support at T2 and depressive symptoms at T3 serially mediated the relationship between resilience at T1 and internalized HIV stigma at T4. Depressive symptoms at a previous time point consistently predicted the levels of internalized HIV stigma at subsequent time points. The study highlights the complex interplay between internalized HIV stigma, mental health problems, and protective factors in a longitudinal context. The findings suggest the need to incorporate interventions aimed at enhancing social support and resilience in mental health programs for PLWH, as these factors may interrupt the pathway from internalized HIV stigma to depressive symptoms and potentially improve the overall psychological well-being of this population. [ABSTRACT FROM AUTHOR]

The purpose of this study was to test the reliability and validity of the Advance Care Planning Engagement Survey-9 Korean version in patients with cardiovascular diseases or metabolic syndrome. In this cross-sectional study, data on advance care planning engagement, registration of advance directives and the intention, and sociodemographic characteristics were collected from 105 patients (mean age, 66.3 years) at 4 medical institutions. Cronbach α was used to test the reliability. Confirmatory factor analysis and independent t tests were used to test the validity. Cronbach αs for the total scale and the self-efficacy and readiness dimensions were .93, . 82, and .97, respectively. In confirmatory factor analysis with 2 factors, all indices of model fit were acceptable: comparative fit index, 0.995; Tucker-Lewis index, 0.989; standardized root-mean-square residual, 0.024; rootmean-square error of approximation, 0.059; and factor loadings > 0.65. Patients who registered advance directives ( P < .001) or had the intention ( P < .001) had higher scores of the Advance Care Planning Engagement Survey-9 Korean version than their counterparts. The findings demonstrate that the Advance Care Planning Engagement Survey-9 Korean version was a reliable and valid instrument. Health care providers, including nurses, can use this instrument to assess and manage advance care planning engagement in Korean patients with cardiovascular diseases or metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Decisions on the frequency of physician encounters for patients with type 2 diabetes mellitus (T2DM) have significant impacts on both patients' health outcomes and burden on health systems, whereas definitive intervals for physician encounters are still lacking in most clinical guidelines. This study systematically reviewed the existing evidence evaluating different frequencies of physician encounters among T2DM patients. Methods: Systematic search of studies evaluating different visit frequencies for follow - up care in T2DM patients was performed in MEDLINE Ovid, Embase Ovid, and Cochrane library from database inception to 25 March 2022. Studies on the follow - up encounters driven by non - physicians and those on the episodic visits in the acute care settings were excluded in the screening. Citation searching was conducted via Google Scholar on the identified papers after screening. The risk of bias was assessed using Cochrane RoB2 tool for randomized controlled trials and Newcastle - Ottawa Scale for cohort studies. Findings were summarized narratively. Results: Among 6363 records from the database search and 231 references from the citation search, 12 articles were eligible for in - depth review. The results showed that for patients who had not achieved cardiometabolic control, intensifying encounter frequency could enhance medication adherence, shorten the time to achieve the treatment target, and improve the patients' quality of life. However, for the patients who had already achieved the treatment targets, less frequent encounters were equivalent to intensive encounters in maintaining their cardiometabolic control, and could save considerable healthcare costs without substantially lowering the quality of care and patients' satisfaction. Conclusion: Existing evidence suggested that the optimal frequency of physician encounters for patients with T2DM should be individualized, which can be stratified by patients' risk levels based on the cardiometabolic control to guide the differential scheduling of physician encounters in the follow - up. More research is needed to determine how to optimize the frequency of physician encounters for this large and heterogeneous population. [ABSTRACT FROM AUTHOR]

Nurses primarily focus on caring for others, but they also require care and support to enhance their own resilience. Thus, this study aims to determine the effects of psychological interventions on nurses' resilience support and to define the influence of moderating variables that can affect these effects. The literature search was conducted in 10 electronic databases, and 5 randomized controlled trials and 10 non-randomized controlled trials were finally selected for analysis (a total of 852 participants). Statistical analyses of the effect sizes and homogeneity of the intervention programs were conducted using RevMan 5.3 from the Cochrane Library and the R program. Publication bias in the retrieved studies was tested using contour-enhanced funnel plots. The meta-analysis found that psychological interventions were effective in improving nurses' resilience immediately after the intervention (SMD = 0.59, 95% CI 0.31 to 0.86, Z = 4.18, p < 0.001) and in the short term within three months (SMD = 1.52, 95% CI 0.74 to 2.31, Z = 3.80, p < 0.001). Interventions using emotion regulation, relaxation, and self-compassion were particularly effective, and the intervention period was effective in both a short period of 1 day and a long period of more than 12 weeks. In addition, the optimal one-session time was 121–150 min, and offline interventions were more effective than online interventions. Furthermore, the effect size was affected by the intervention time for one session (QB = 12.02, df = 3, p = 0.007) and the on/offline intervention method (QB = 5.85, df = 1, p = 0.015). These findings may inform the development of targeted interventions and resilience support systems for nurses. However, in the future, more rigorous studies, such as randomized controlled trials, should be conducted to ensure strict control over the variables and to establish a stronger evidence base for the effectiveness of these interventions. [ABSTRACT FROM AUTHOR]

Objective. Brief, reliable, and cost-effective methods to assess parenting are critical for advancing parenting research. Design. We adapted the Three Bags task and Parent Child Interaction Rating System (PCIRS) for rating online visits with 219 parent–child dyads (White, n = 104 [47.5%], Black, n = 115 [52.5%]) and combined the video data with survey data collected during pregnancy and when children were aged 1. Results. The PCIRS codes of positive regard, stimulation of child cognitive development, and sensitivity showed high reliability across the three parent–child interaction tasks. A latent positive parenting factor combining ratings across codes and tasks showed good model fit, which was similar regardless of parent self-identified race or ethnicity, age, socioeconomic disadvantage, marital/partnered status, and parity, as well as methodological factors relevant to the online video assessment method (e.g., phone vs. laptop/tablet). In support of construct validity, observed positive parenting was related to parent-reported positive parenting and child socioemotional development. Finally, parent reports of supportive relationships in pregnancy but not neighborhood safety or pandemic worries, were prospectively related to higher positive parenting observed at age 1. With the exception of older parental age and married/partnered status, no other parent, child, sociodemographic, or methodological variables were related to higher overall video exclusions across tasks. Conclusions. PCIRS may provide a reliable approach to rate positive parenting at age 1, providing future avenues for developing more ecologically valid assessments and implementing interventions through online encounters that may be more acceptable, accessible, or preferred among parents of young children. [ABSTRACT FROM AUTHOR]

Objective: Fibroblast‐like synoviocytes (FLSs) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLSs in relapse and remission of RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease‐modifying antirheumatic drugs. Methods: Combining single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three patients with relapse RA and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using quantitative real‐time PCR (qPCR) and multiplex immunohistochemistry (mIHC). We further targeted the critical signals in vitro and in vivo using the collagen‐induced arthritis (CIA) model in rats. Results: Lining and sublining FLS subsets were identified using scRNA‐seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLSs from patients with relapse RA for which mIHC confirmed the increased expression of FGF10. Although the type I interferon pathway was also activated in the lining FLSs, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by small interfering RNA in FLSs significantly reduced the expression of receptor activator of NF‐κB ligand. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human‐derived pannus cell culture, whereas the FGF receptor (FGFR) 1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model. Conclusion: The FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue‐specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation may be a potential mechanism of postoperative delirium (POD) in geriatric patients, and hypertonic saline (HS) has immunomodulatory properties. The purpose of this study was to investigate whether HS could reduce the incidence of POD in elderly patients and its effect on neutrophil activation and inflammatory cytokine expression. Methods: We studied the effect of pre-infusion of 4 mL/kg 3% hypertonic saline vs. 4 mL/kg 0.9% normal saline on POD in patients undergoing shoulder arthroscopy in a prospective, randomized, double-blind, controlled trial. Neutrophil surface molecules (CD11b, CD66b and CD64) were analyzed by flow cytometry. Circulating concentrations of inflammatory factors IL-1β, IL-6, TNF-α and neurological damage factor S100β were assessed by enzyme immunoassay. The Confusion Assessment Method-Chinese Revision (CAM-CR) was applied for the assessment of POD 1–3 days after surgery. Results: The incidence of POD in group H was significantly lower than that in group N (7.14% vs 26.83%, P = 0.036). The expression levels of inflammatory cytokines (IL-6 and TNF-α) and neutrophil surface markers (CD11b and CD66b) were significantly lower in group H than in group N at 24 h after surgery (P = 0.018, P < 0.001, P < 0.001, P = 0.024). There were no significant differences in postoperative pain, nausea and vomiting, infection, phlebitis, and patients satisfaction between the two groups. Conclusion: Pre-infusion of HS can reduce the incidence of POD and the immune-inflammatory response. Trial registration: Chinese Clinical Trial Registry (14/4/2022, registration number: ChiCTR2200058681. [ABSTRACT FROM AUTHOR]

The study investigated the influence of the humanistic orientation on the perspectives of service providers working with individuals with intellectual and developmental disabilities (IDD) and the self‐evaluation of service users. The humanistic orientation, which emerged in the 1990s, emphasizes the rights of people with IDD to lead a meaningful life based on their personal needs and desires. However, challenges persist as some service providers prioritize the acquisition of normative life skills over fostering autonomy. The study was based on quantitative methodology and included 61 service providers and 95 of their service users. The study's findings indicate that the humanistic orientation was endorsed by nearly one half of the service providers compared with one third who endorsed a medical orientation. Those endorsing a humanistic orientation also reported that their service users had higher levels of efficacy than those with a medical perception of IDD. Positive correlations were found regarding the assessments made by service providers and their service users on self‐efficacy. Findings suggest that a humanistic orientation encourages optimism among service providers and a positive dyadic interaction between providers and users. It is suggested that the humanistic orientation be applied as a guiding principle underlying the daily support provided to adults with IDD. [ABSTRACT FROM AUTHOR]

Background: In recent years, breast cancer has become the most common cancer in the world, increasing women's health risks. Approximately 60% of breast cancers are categorized as human epidermal growth factor receptor 2 (HER2)-low tumors. Recently, antibody-drug conjugates have been found to have positive anticancer efficacy in patients with HER2-low breast cancer, but more studies are required to comprehend their clinical and molecular characteristics. Methods: In this study, we retrospectively analyzed the data of 165 early breast cancer patients with pT1-2N1M0 who had undergone the RecurIndex testing. To better understand HER2-low tumors, we investigated the RecurIndex genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status. Results: First, there were significantly more hormone receptor (HR)-positive tumors, luminal-type tumors, and low Ki67 levels in the HER2-low than in the HER2-zero. Second, RI-LR (P =.0294) and RI-DR (P =.001) scores for HER2-low and HER2-zero were statistically significant. Third, within HER2-negative disease, HR-positive/HER2-low tumors showed highest ESR1, NFATC2IP, PTI1, ERBB2, and OBSL1 expressions. Fourth, results of the survival analysis showed that lower expression of HER2 was associated with improved relapse-free survival for HR-positive tumors, but not for HR-negative tumors. Conclusions: The present study highlights the unique features of HER2-low tumors in terms of their clinical characteristics as well as their gene expression profiles. HR status may influence the prognosis of patients with HER2-low expression, and patients with HR-positive/HER2-low expression may have a favorable outcome. In this study, the data of patients with early stage breast cancer who had undergone RecurIndex testing was analyzed. To better understand HER2-low tumors, genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status were investigated. [ABSTRACT FROM AUTHOR]

Objectives: The prognostic significance of CDC42 effector protein 2 (CDC42EP2) and its association with tumor-infiltrating immune cells (TIICs) have not been explored in liver hepatocellular carcinoma (LIHC). This study aims to assess the potential prognostic value of CDC42EP2 by conducting a comprehensive analysis of online databases pertaining to LIHC. Methods: We evaluated the potential of CDC42EP2 as a prognostic biomarker by utilizing online databases such as TIMER, GEPIA2, KM, OSlihc, HPA, and LinkedOmics. Results: In LIHC, we observed that the mRNA and protein expression of CDC42EP2 were upregulated compared to normal tissues. Upregulated CDC42EP2 expression was associated with a worse prognosis based on the clinicopathological characteristics of patients with LIHC. Furthermore, CDC42EP2 was positively associated with TIICs. In the co-expression and functional enrichment analyses of CDC42EP2, 11,416 genes showed positive associations with CDC42EP2 while 8,008 genes showed negative associations. CDC42EP2-related co-expression genes were involved in protein localization to the endoplasmic reticulum, translational initiation, and RNA catabolic processes in gene set enrichment analysis-Gene Ontology (GSEAGO), and regulated the ribosome, spliceosome, and primary immune deficiency in the GSEAKyoto Encyclopedia of Genes and Genomes (KEGG) pathway. In a survival map, 23 and 17 genes that exhibited positive associations with CDC42EP2 showed a significant hazard ratio (HR) for overall survival and disease-free survival, respectively. Conclusion: Our findings demonstrated that CDC42EP2 is a novel prognostic biomarker and a potential tumor immune therapeutic target in patients with LIHC. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches. Methods: In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. Results: We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially. Conclusions: While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the clinical efficacy and safety of percutaneous endoscopic interlaminar discectomy (PEID) for treating highly downward-migrated disc herniation. Methods: We conducted a retrospective study on 39 patients with highly downward-migrated disc herniation who underwent PEID treatment between January 2015 and October 2020. The clinical outcomes, including the preoperative and postoperative visual analogue scale (VAS) for the back and leg, Oswestry Disability Index (ODI), and MacNab criteria for surgical success, were evaluated and compared to thirty-seven patients treated with posterior lumbar interbody fusion (PLIF). Results: The mean operation time of PEID was 93.00(77.00,110.00) min, while that of PLIF was 169.00(157.00,183.00) min. Continued improvement in both PEID and PLIF was observed in the VAS and ODI scores immediately after the surgery to the last follow‐up. The VAS and ODI scores of PEID one week after surgery were significantly different from those of PLIF. One patient with recurrent lumbar disc herniation in the same segment improved after undergoing repeat PEID, two patients had dura tears, and conservative treatment helped relieve the symptoms. The overall percentage of patients with good to excellent results of PELD according to the modified MacNab criteria was 97.43%, while that of PLIF was 94.60%. Conclusions: PEID has reliable efficacy and safety for treating highly downward-migrated disc herniation. And the long-term efficacy of PEID is comparable to PLIF. No severe complications occurred after surgery, and most patients' symptoms were relieved. [ABSTRACT FROM AUTHOR]

Preoperative knowledge of expected postoperative pain can help guide perioperative pain management and focus interventions on patients with the greatest risk of acute pain. However, current methods for predicting postoperative pain require patient and clinician input or laborious manual chart review and often do not achieve sufficient performance. We use routinely collected electronic health record data from a multicenter dataset of 234,274 adult non-cardiac surgical patients to develop a machine learning method which predicts maximum pain scores on the day of surgery and four subsequent days and validate this method in a prospective cohort. Our method, POPS, is fully automated and relies only on data available prior to surgery, allowing application in all patients scheduled for or considering surgery. Here we report that POPS achieves state-of-the-art performance and outperforms clinician predictions on all postoperative days when predicting maximum pain on the 0–10 NRS in prospective validation, though with degraded calibration. POPS is interpretable, identifying comorbidities that significantly contribute to postoperative pain based on patient-specific context, which can assist clinicians in mitigating cases of acute pain. [ABSTRACT FROM AUTHOR]

Background: Notopterygii Rhizoma et Radix (NRR) is commonly used for the treatment of inflammation-linked diseases. Phenethylferulate (PF) is high content in NRR crude, but its anti-inflammatory effect remains unclear. Therefore, we aimed to investigate the anti-inflammatory properties of PF and its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: The effect of PF on cell viability was measured by MTT assay. The anti-inflammatory properties of PF were studied by detecting the levels of inflammatory mediators and cytokines using enzyme-linked immunosorbent assay (ELISA). Furthermore, the anti-inflammatory mechanisms of PF were determined by Western blot analysis. Results: PF was not cytotoxic to RAW 264.7 macrophages at the concentrations of below 48 μM. ELISA showed that PF conspicuously inhibited overproduction of prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Western blot analysis showed that PF remarkably suppressed overproduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), the phosphorylation of inhibitor of NF-κB kinase α (IκB-α), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38, as well as the degradation and subsequent nuclear translocation of p65. Conclusions: PF is a potent inhibitor of inflammation acting on nuclear factor kappa-B (NF-κB), Akt and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-stimulated RAW 264.7 macrophages. This work provides evidence for the suitability of PF as a therapeutic candidate for the management of inflammatory-mediated immune disorders. [ABSTRACT FROM AUTHOR]

Individuals with depressive symptoms are vulnerable to COVID-19 infection and mortality; therefore, their vaccination status must be investigated to reduce these rates. This study investigated the association between depressive symptoms and COVID-19 vaccine uptake and intention and identified the reasons for vaccine avoidance. Data were collected from the 2021 Korea Community Health Survey and analyzed using logistic regression. A statistically significant association was found between the presence of depressive symptoms and no COVID-19 vaccine uptake. Among individuals who reported experiencing depression, 4.6% were unvaccinated and 7.7% reported no intention to get vaccinated. Among the unvaccinated, the adjusted odds ratio (aOR) for depression was 1.53 (95% confidence interval: 1.45–1.61) compared to the vaccinated. Similarly, a significant association was observed between depressive symptoms and no intention to get vaccinated. In the group with no vaccine intention, the aOR for depression was 2.06 (95% CI: 1.86–2.27) compared to the group with vaccine intention. Furthermore, "health-related reasons" and "concerns about side effects or past experience of side effects" accounted for 89% of the reasons for vaccine avoidance among individuals with depression. Therefore, it is important to provide tailored information and develop programs to increase awareness and promote COVID-19 vaccine uptake among these individuals. [ABSTRACT FROM AUTHOR]

Background: Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate. Objective: To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis. Methods: Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I2 statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. Results: A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I2=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I2=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I2=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I2=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence. Conclusion: Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430) [ABSTRACT FROM AUTHOR]

Background: Blended learning is increasingly being adopted, and yet a gap remains in the related literature pertaining to its skill performance, learning engagement and inner experience in undergraduate surgical nursing skills course. Objectives: To investigate the changes in skills performance and learning engagement in the application of blended learning, and what it actually brings to nursing students. Design: The study uses a historical control, two-armed, mixed and quasi-experimental design. Methods: The blended learning version of the course was offered to the 2019 class of 334 nursing undergraduates. Quantitative and qualitative data were collected after the course to obtain a comprehensive understanding of the course effects compared with the 304 nursing undergraduates of grade 2017 who adapted traditional learning. Quantitative data were analyzed by descriptive and inferential statistics using IBM SPSS 26.0, and qualitative data were encoded using Nvivo11.0. Results: There were significant differences in skill performance and learning engagement between the class of 2017 and 2019 (p < 0.001). Combined with further analysis of the interview data, 3 first-level nodes and 8 secondary nodes were determined. Students' opinions, comments and suggestions on the application of blended learning are refreshing. Conclusion: Moving forward with blended learning: opportunities and challenges go hand in hand. Researchers need to continually modify their research designs to respond to variable educational environments. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between type 2 diabetes mellitus (T2DM) patients' attitude, subjective norms (SN), perceived behavioral control (PBC), behavioral intention (BI) and behavior associated with integrated treatment and preventive (ITP) services. Methods: A convenient sampling method was employed at a community health center in Nanjing, China between January and July 2022. The collected data were processed using Epidata 3.1, SPSS 26.0, and AMOS 24.0. Descriptive statistics and a structural equation model based on the theory of planned behavior (TPB) were used to explore the correlation between the study variables. Results: 430 participants were eventually included, with a response rate of 98.6%. The mean age was 72.50 ± 5.69 years. The TPB model proved to be suitable and explained 41% of the variance in the BI. Attitude (β = 0.289, P < 0.001), SN (β = 0.314, P < 0.001) and PBC (β = 0.261, P < 0.001) were the main predictors of BI, and the SN was the strongest. BI (β = 0.452, P < 0.001) and PBC (β = 0.452, P < 0.001) had similar direct effects on patients' behavior. Conclusion: The TPB model explained the behavioral variations associated with ITP services and provided a framework for developing targeted interventions and improving community-based ITP services for T2DM. To encourage patients to engage in desirable behaviors, interventions should focus on modifying patients' SN towards behavior associated with ITP services by promoting peer pressure and increasing the family's emphasis on health. [ABSTRACT FROM AUTHOR]

Background: Chronic primary pain (CPP) is an intractable pain of unknown cause with significant emotional distress and/or dysfunction that is a leading factor of disability globally. The lack of a suitable animal model that mimic CPP in humans has frustrated efforts to curb disease progression. 2R, 6R-hydroxynorketamine (2R, 6R-HNK) is the major antidepressant metabolite of ketamine and also exerts antinociceptive action. However, the analgesic mechanism and whether it is effective for CPP are still unknown. Methods: Based on nociplastic pain is evoked by long-term potentiation (LTP)-inducible high- or low-frequency electrical stimulation (HFS/LFS), we wanted to develop a novel CPP mouse model with mood and cognitive comorbidities by noninvasive low-frequency percutaneous electrical nerve stimulation (LF-PENS). Single/repeated 2R, 6R-HNK or other drug was intraperitoneally (i.p.) or intrathecally (i.t.) injected into naïve or CPP mice to investigate their analgesic effect in CPP model. A variety of behavioral tests were used to detect the changes in pain, mood and memory. Immunofluorescent staining, western blot, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and calcium imaging of in cultured dorsal root ganglia (DRG) neurons by Fluo-8-AM were used to elucidate the role and mechanisms of 2R, 6R-HNK in vivo or in vitro. Results: Intrathecal 2R, 6R-HNK, rather than intraperitoneal 2R, 6R-HNK or intrathecal S-Ketamine, successfully mitigated HFS-induced pain. Importantly, intrathecal 2R, 6R-HNK displayed effective relief of bilateral pain hypersensitivity and depressive and cognitive comorbidities in a dose-dependent manner in LF-PENS-induced CPP model. Mechanically, 2R, 6R-HNK markedly attenuated neuronal hyperexcitability and the upregulation of calcitonin gene-related peptide (CGRP), transient receptor potential ankyrin 1 (TRPA1) or vanilloid-1 (TRPV1), and vesicular glutamate transporter-2 (VGLUT2) in peripheral nociceptive pathway. In addition, 2R, 6R-HNK suppressed calcium responses and CGRP overexpression in cultured DRG neurons elicited by the agonists of TRPA1 or/and TRPV1. Strikingly, the inhibitory effects of 2R, 6R-HNK on these pain-related molecules and mechanical allodynia were substantially occluded by TRPA1 antagonist menthol. Conclusions: In the newly designed CPP model, our findings highlighted the potential utility of intrathecal 2R, 6R-HNK for preventing and therapeutic modality of CPP. TRPA1-mediated uprgulation of CGRP and neuronal hyperexcitability in nociceptive pathways may undertake both unique characteristics and solving process of CPP. Highlights: 1) We first establish the CPP mouse model by LF-PENS to mimic nociplastic pain. 2) Intrathecal 2R, 6R-HNK effectively alleviates LF-PENS-induced CPP in mouse models by inhibiting TRPA1 in DRG neurons. [ABSTRACT FROM AUTHOR]