Annals of Medicine

Purpose To prepare a polyglycolic acid-loaded mitomycin drug (MMC-ATS-@PLGA) to inhibit scar proliferation after glaucoma filtering surgery (GFS) via an anti-inflammatory mechanism that minimally affected intraocular pressure, which provided another therapeutic strategy for this disease. Methods We first detected the physicochemical properties of MMC-ATS-@PLGA. Next, we tested the biosafety of MMC-ATS-@PLGA in vivo and in vitro. Then, we assessed the therapeutic effects of MMC-ATS-@PLGA by laboratory and clinical examinations. Results In this study, we synthesized a new type of nanomedicine (MMC-ATS-@PLGA) with good stability and biocompatibility for inhibiting scar proliferation after GFS. The break-up time (BUT), Schimer test and intraocular pressure changes in GFS rabbits before and after treatment with MMC-ATS-@PLGA were not significantly different. Three weeks after GFS, the MMC-ATS-@PLGA group displayed significant decreases in nuclear volume, corneal cell oedema, type I and III collagen fibre expression, normal organelle morphology and collagen fibre arrangement. Compared with those in the FML and MMC groups, the α-SMA, CTGF and type III collagen fibres in the MMC-ATS-@PLGA group decreased more significantly, indicating that MMC-ATS-@PLGA can effectively inhibit the expression of these inflammatory factors during the inhibition of scar proliferation after GFS. Conclusion We successfully synthesized MMC-ATS-@PLGA, which could effectively inhibit scar proliferation after GFS via anti-inflammatory effects but had little effect on intraocular pressure. This new type of nanomedicine has good biosafety and stability and is worthy of further exploration in clinical practice.

Introduction Fatigue and excessive daytime sleepiness (EDS) frequently affect interstitial lung disease (ILD) patients, while studies are limited. The study aims to determine the prevalence and contributing factors of fatigue and EDS in ILD patients. Methods This was a cross-sectional study. Consecutive patients diagnosed with ILD at the Second Xiangya Hospital of Central South University were recruited, and healthy volunteers were recruited as controls. Fatigue Assessment Scale and Epworth Sleepiness Scale scores were the basis for judging fatigue and EDS. The prevalence of fatigue and EDS between ILD patients and healthy volunteers were compared, and the differences in clinical characteristics between ILD patients with and without fatigue/EDS were analyzed. Binary logistic regression was used to analyze the correlation factors of fatigue and EDS. Results In this study, 92 healthy volunteers and 108 ILD patients were recruited. The prevalence of fatigue and EDS was higher in ILD patients than in healthy volunteers (40.7% vs 9.8%, 35.2% vs 14.1%). ILD patients with fatigue showed significantly worse pulmonary diffusion function and exercise tolerance, alongside reduced quality of life, and increased instances of EDS, anxiety, and depression. Patients with EDS were older than non-EDS patients (68.5 vs 61.5 years; p = 0.038) and had a higher prevalence of fatigue and depression, along with decreased quality of life. Multivariable logistic regression identified chest pain/oppression and diminished exercise capacity as factors linked to fatigue, and age over 60 years and diminished exercise capacity as factors associated with EDS. Conclusion ILD patients experience a higher prevalence and more severe impact of fatigue and EDS than healthy individuals, with associated factors including chest pain, diminished exercise capacity, and age. Pulmonary rehabilitation and evaluation and intervention of factors associated with fatigue and EDS such as pain, and diminished exercise capacity in ILD patients may help to improve the quality of life.

Background Many publications have reported that acute COVID-19 infection can cause autonomic dysfunction. In this series, we described seven patients who had recurrent fever after acute COVID-19 infection, and the possible pathophysiological basis is autonomic dysfunction. Patients This was a retrospective study conducted at the Qilu Hospital of Shandong University from January 2023 to March 2023. Patients who were hospitalized in the Department of Infectious Diseases with a diagnosis of fever of unknown origin. Results Between January and March 2023, a total of seven patients with autonomic dysfunction in post-COVID condition, who had recurrent fever accompanied by electrolyte imbalances and other manifestations of autonomic dysfunction. The median age of these patients was relatively high, and they were mostly indoor workers with comorbidities such as diabetes and chronic hypertension. Physical cooling and correction of electrolyte imbalances with medication were effective treatments. Conclusions The COVID-19 infection can lead to autonomic dysfunction, which manifests not only as tachycardia and blood pressure abnormalities, but may also be the pathophysiological mechanism underlying recurrent fever in post-COVID cases.

Objective This study aims to assess the robustness of cardiovascular disease randomized controlled trials (RCTs) with primary continuous outcomes from a clinical perspective, utilizing the concepts of continuous fragility index (CFI), reverse continuous fragility index (RCFI) and their corresponding quotients (CFQ, RCFQ). Methods A cross-sectional study was conducted, searching PubMed for cardiovascular RCTs published between January 1, 2018, to December 31, 2022, in eight high-impact journals. Inclusion criteria were phase III or IV trials with 1:1 randomization, reporting at least one primary continuous outcome. Data analysis involved altering each outcome until achieving the reversal of significance (ɑ = 0.05) to determine the CFI or RCFI. The fragility quotients were then calculated by dividing the CFI or RCFI by the sample size, and Spearman’s correlation assessed correlation analyses. Results Of 3983 records were screened, and 64 RCTs (76 outcomes) were included. The fragility index was analysed with 72 outcomes. The overall median CFI was 7, with an associated median CFQ of 0.032. Nonsignificant P values exhibited greater statistical instability (median RCFI = 5, RCFQ = 0.023) than significant P values (median CFI = 14, CFQ = 0.062). Interestingly, “fragile” values were found in 36% (9/25) of CFI or 46.7% (7/15) of RCFI. Additionally, fragility index showed a significant association with several variables. Conclusions The findings suggest that changing only a small number of interventions (median of 7) could alter outcome significance. Reporting the fragility index alongside P values is recommended to provide a clearer understanding of statistical findings’ robustness. Highlights The continuous fragility index (CFI) represents the minimum patient count needed to modify significance by altering their intervention. Among 72 primary continuous outcomes in 64 cardiovascular RCTs, the overall median CFI was 7, with a corresponding CFQ of 0.032. CFI demonstrated moderate to strong correlations with sample size, total dropouts, and patient numbers analyzed.

Purpose Adrenocortical carcinoma (ACC) afflicts both pediatric and adult populations and is characterized by dismal prognosis and elevated mortality. Given the inconsistent therapeutic benefits and significant side effects associated with the conventional chemotherapy agent, mitotane, and the nascent stage of immunotherapy and targeted treatments, there is an urgent need to identify novel prognostic biomarkers and therapeutic targets in ACC. Methods Utilizing multi-omic datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), we employed Weighted Gene Co-expression Network Analysis (WGCNA), Cox regression, Receiver Operating Characteristic (ROC) curves, and survival analyses to sift for potential prognostic biomarkers. We subsequently validated these findings through immunohistochemistry and cell assays, and delved into the biological role of KPNA2 in ACC through functional enrichment analysis, mutational landscape, and immune cell infiltration. Results A total of 77 progression-associated genes with aberrant chromosomal accessibility were discerned within the TCGA-ACC dataset. By integrating ROC and Cox regression from GEO datasets, KPNA2 emerged as an independent risk factor portending poor outcomes in ACC. ATAC-seq analysis revealed attenuated chromatin accessibility of KPNA2 in cases with unfavorable prognosis. Immunohistochemistry corroborated elevated KPNA2 expression, which was linked to enhanced proliferation and invasion. Elevated KPNA2 levels were found to activate oncogenic pathways while simultaneously suppressing immunological responses. Immune infiltration analysis further revealed a decrement in CD8+ T-cell infiltration in KPNA2-high cohorts. Conclusion This study demonstrates the clinical and biological significance of KPNA2 in ACC and suggests that KPNA2 could serve as a promising biomarker for predicting prognosis and immunotherapeutic responses in pediatric and adult ACC patients.

Background Little is known regarding long-term consequences (≥5 years) of sport-related concussion (SRC) sustained during adolescence. Adolescent SRC has been linked to athlete considerations of sport participation and subsequent retirement from sport during this critical developmental period. Prolonged SRC symptoms can reduce ability to perform physical activity, and research suggests inactivity can extend years post-injury. Therefore, SRC may affect long-term physical activity, which may result in decreased cardiorespiratory fitness and increased adiposity. Objectives (1) To examine cardiorespiratory fitness, adiposity and associations with physical activity between three groups: adolescent SRC 5–15 years prior; adolescent musculoskeletal injury (MSK) 5–15 years prior; and individuals who played adolescent sport but were uninjured. (2) To explore whether biological sex-modified relationships assessed by the primary objective. Methods Young adults (16–33 years old) who sustained SRC (n = 54) or MSK (n = 52) during adolescent sport and uninjured individuals (n = 50) were recruited (n = 156) from previous Sport Injury Prevention Research Centre studies and word-of-mouth. Participants completed a cycle-ergometer maximal exertion test, dual-energy X-ray absorptiometry scanning, and wore actigraphs for 1-week post-testing. Outcome measures of cardiorespiratory fitness [peak oxygen consumption (VO2peak[ml/min])] and adiposity [fat mass index (FMI)] were examined in relation to cohort, sex, time since injury, lean mass index and moderate-to-vigorous physical activity [daily MVPA (min)] via multiple linear regression. Results In relation to the uninjured cohort, MSK (mean difference = 297.14 ml/min; β = 2.88; 95%CI: 0.99–4.76, p = 0.003) and SRC (mean difference = 268.01 ml/min; β = 2.61; 95%CI: 0.77–4.44, p = 0.006) cohorts demonstrated higher VO2peak and this did not differ based on biological sex. FMI did not differ for MSK (mean difference= −0.10 kg/m²; β= −0.02; 95%CI: −0.22–0.18, p = 0.847) or SRC (mean difference=-0.22 kg/m²; β= −0.05; 95%CI: −0.24–0.15, p = 0.642) cohorts relative to the uninjured cohort for both males and females. Conclusions It is possible to maintain adequate long-term cardiorespiratory fitness and adiposity following adolescent SRC relative to those who only sustained sport related MSK injuries or did not sustain significant injuries as adolescents/adults.

Background Within normal variation, higher haemoglobin (Hb) levels are associated with unhealthier body composition, adverse metabolism and cardiovascular disease (CVD)-related mortality. Global longitudinal strain (GLS) is a direct, well validated and reproducible echocardiographic measure for the evaluation of cardiac contractile function, providing additional prognostic value for prediction of a variety of cardiac events. This study investigated the relation between Hb levels and cardiac function measures, including GLS, in a Finnish midlife population. Materials and methods Echocardiography was carried out in a subpopulation of the Northern Finland Birth Cohort 1966 at age of 46 (n = 1155). GLS was available for n = 796. Subjects with diabetes, severe cardiac diseases, echocardiographic abnormalities, heart rate ≥85 bpm during echocardiography or Hb level outside the Finnish reference intervals (117–155 g/L for females and 134–167 g/L for males) were excluded from the analysis. The study population included 635 subjects (46% males). The data were analysed in Hb tertiles and in multivariable linear regression models. Results The highest Hb tertile had adverse anthropometric and metabolic parameters compared to other Hb tertiles. Of the studied echocardiographic parameters, the highest Hb tertile had the highest left ventricular mass (LVM, p < .01), LVM index (LVMi, p < .05), LV end-diastolic volume (LVEDV, p < .05), posterior wall thickness (PWT, p < .001), relative wall thickness (RWT, p < .05) and the lowest absolute GLS (p < .001) but no difference in LV ejection fraction (LVEF) was observed between the Hb tertiles. In linear models, when adjusted for covariates, Hb levels were associated positively and independently with GLS (B = 0.153 [0.071; 0.235]) and LVM (B = 0.272 [0.193; 0.350]). Conclusions Higher Hb levels are associated with an adverse metabolic and inflammatory profile and more adverse cardiac function measures, including GLS, in both sexes in midlife.

Background Most patients with lumbar disc herniation can be relieved or cured by surgical or non-surgical treatment; however, postoperative persistent radiculopathy is common. This study demonstrates the regulation of autophagy by the FOXG1/SATB2 axis in lumbar disc herniation (LDH). Methods Rat dorsal root neurons were induced with TNF-α in vitro. Sprague Dawley (SD) rats were used to construct the LDH rat model, which was treated with L. paracasei S16 or oe-FOXG1. Paw withdrawal threshold or latency assay (PWT/L) was performed. Peripheral blood samples were collected and analysed using ELISA and miRNAseq. RT-qPCR was used to analyse the expression of FOXG1, LC3B, Beclin1, p62, and SATB2. TUNEL staining and flow cytometry were used to analyse apoptosis. The expression of Cyclin D1, PCNA, Ki67, FOXG1, SATB2, and autophagy proteins was measured using western blotting. Results TNF-α induced low expression of FOXG1 and SATB2 in dorsal root ganglion (DRG) neurons of rats. TNF-α induced an increase in p62 protein and a decrease in LC3II/I and Beclin-1 proteins in neurons, which were blocked by oe-FOXG1. oe-FOXG1 suppressed inflammation and apoptosis in TNF-α-induced DRG neurons and LDH rats and promoted the expression of Cyclin D1, PCNA, and Ki67. Many miRNAs were increased in the peripheral blood of LDH rats, but decreased after L. paracasei S16 intervention. L. paracasei S16 affects miR-31a-5p and SATB2 expression. Dual luciferase reporter gene assay confirmed that miR-31a-5p bound to SATB2. Co-IP analysis confirmed the interaction between FOXG1 and SATB2. Silencing of SATB2 inhibited the beneficial effects of oe-FOXG1 in TNF-α-induced dorsal root ganglion neurons. Animal experiments further demonstrated that oe-FOXG1 improved LDH disease characteristics by downregulating PWT, PWL, inflammation, and apoptosis levels and upregulating SATB2-autophagy levels. Conclusions MiR-31a-5p/SATB2 is involved in the treatment of L. paracasei S16 in LDH rats. Overexpression of FOXG1 promotes autophagy through SATB2 to improve LDH levels This provides a new approach for the treatment of LDH.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the central nervous system. Despite a large number of studies, the current prognosis of ALS is still not ideal. This article briefly describes the clinical features including epidemiology, genetic structure and clinical manifestations, as well as the progress of new diagnostic criteria and treatment of ALS. Meanwhile, we also discussed further both developments and improvements to enhance understanding and accelerating the introduction of the effective treatments of ALS.

Objective Astilbe chinensis, is a traditional Chinese medicine commonly employed for pain management. However, its primary active ingredient remains a subject of debate. Methods Spinal nerve ligation (SNL) and formalin-induced pain models were employed. Network pharmacology and bioinformatics were utilized to identify targets. Verification was performed through spinal cord double immunofluorescence staining, quantitative PCR and whole-cell recording techniques. Results In experiments conducted on neuropathic rats, both systemic and intrathecal administration of astilbin, an essential constituent, exhibited a noteworthy and dose-dependently decrease in chronic and acute pain behaviours. The ED50 value, which represents the dose at which 50% effectiveness is achieved, was measure at 7.59 μg, while the Emax value, indicating the maximum attainable effect, was found to be 60% of the maximal possible effect (% MPE). Forty-two shared targets were identified, enriching the metabolic and synaptic pathways in the network pharmacology analysis, as confirmed by transcriptomic analysis. Weighted gene co-expression network analysis (WGCNA) revealed a strong correlation between the anti-nociceptive effects of astilbin and neuronal metabolic processes. Spinal functional ultrasound (FUS) analysis indicated increased spinal blood flow intensity and changes in metabolism-related enzyme activity, including stearoyl-CoA desaturase (Scd), 17beta-hydroxysteroid dehydrogenase (Hsd17b7) and sterol 14alpha-demethylase (Cyp51) in neuropathic rats, pretreatment with astilbin decreased formalin-induced blood flow in acute pain. Bath application of astilbin dose-dependently inhibited neuronal activity by reducing the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) without affecting miniature inhibitory postsynaptic currents (mIPSCs). Conclusions In summary, this study provides evidence that astilbin alleviates pain by modulating neuronal metabolic processes and synaptic homeostasis.

Background Factor Xa inhibitors (FXaI) are recommended for treatment of venous thromboembolism (VTE). However, in FXaI trials there is a 2–3% treatment failure rate. This observational study aimed to elucidate factors associated with recurrent VTE during coagulation FXaI treatment. Methods Ten consecutive FXaI failure cases were included. Various thrombosis risk scores were assessed, thrombophilia was screened, and coagulation activity was followed-up, to tailor individual anticoagulation strategies. Results Our patients were young (mean age 37.5 years, range 22–55), six being women. Index VTE was pulmonary embolism (PE) in eight patients, and upon recurrent PE, six of them developed chronic thromboembolic pulmonary hypertension (CTEPH). Although initially many patients appeared to have unprovoked VTE, all had major VTE risk factors. Seven patients had chronic venous obstruction: five subclavian (thoracic outlet syndrome, TOS) even though only two had upper extremity deep vein thrombosis at index thrombosis, plus one common iliac, and one with chronic paraplegia. Five patients had multiple VTE risk factors and four had thrombophilia. VTE risk scores varied from the lowest (TOS patients) to the highest risk (multiple risk factors/thrombophilia). FXaI failure occurred on average at 97 days of therapy (range 15–279) without evident noncompliance. D-dimer levels declined from the index thrombosis to FXaI failure, and re-thrombosis resisted further anticoagulation, low D-dimer referring to impaired fibrinolysis. The majority (8/10) of patients required mechanical/surgical interventions. Conclusions Our results underline careful risk assessment upon PE and reoccurrence, with inclusion of TOS as a risk factor of VTE and CTEPH.

Background Diffuse large B-cell lymphoma (DLBCL), the most prevalent type of non-Hodgkin’s lymphoma, exhibits significant correlations with efferocytosis-related molecules (ERMs) concerning invasion, metastasis, and clinical outcomes. This study aims to establish an efferocytosis-related gene signature specifically linked to DLBCL. Methods Key module genes linked to DLBCL were identified via weighted gene co-expression network analysis (WGCNA) in GSE32018. Univariate Cox analysis of GSE31312 revealed ERMs associated with DLBCL survival. Differential expression analysis identified differentially expressed genes (DEGs) between DLBCL subtypes and normal samples. Venn diagram analysis identified common DEGs and key module genes. A DLBCL gene signature was built by using univariate Cox and least absolute shrinkage and selection operator (LASSO) analysis. Gene functional enrichment, immune microenvironment, and immunotherapy analyses compared two risk subgroups. Prognostic gene expression was validated at the single-cell level. Results In the GSE32018 dataset, 1760 key module genes related to DLBCL were identified. Using GSE31312, 14 ERMs associated with DLBCL prognosis were determined.Then, an ERMs-related prognostic signature, including small nuclear ribonucleoprotein polypeptides B (SNRPB) and centrosomal protein 290 (CEP290), was established. Independent prognostic analysis showed that the RiskScore derived from this signature was a prognostic factor. Significant immune microenvironment differences were observed between two risk subgroups. Additionally, chemotherapeutic drug sensitivity results indicated the signature could predict therapeutic response. Eventually, expression of SNRPB and CEP290 was confirmed in B cells. Conclusion The prognostic signature comprised of SNRPB and CEP290 based on ERMs-DEGs was established, providing a theoretical basis and reference value for DLBCL research.

Background Due to its rarity, it is challenging to predict the survival of patients with synchronous multiple primary esophageal squamous carcinomas (SMPESCs). We aimed to construct nomograms to predict survival outcomes and help to make therapeutic strategy for patients with SMPESCs. Materials and Methods The clinical and survival data of 135 patients with SMPESCs were analyzed retrospectively. Univariate and multivariate Cox analyses were used to identify independent prognostic factors. Nomograms were constructed to predict 1-year, 3-year and 5-year disease-free survival (DFS) and overall survival (OS). In addition, we further evaluated the effect of postoperative adjuvant therapy on SMPESCs patients with lymph node metastasis. Results In univariate and multivariate analyses of DFS and OS, age, site of the main lesion, lymph node metastasis, total number of lymph nodes dissected, lactate dehydrogenase level and lymphocyte-to-monocyte ratio were identified as independent prognostic factors. These characteristics were further included to establish nomograms. For the internal validation of the nomogram predictions of survival outcomes, the concordance indices were 0.752 and 0.756, respectively. Decision curve analysis also proved the efficacy of the nomograms. Furthermore, adjuvant therapy had a statistically significant benefit for OS but not DFS in patients with lymph node metastasis. Conclusions These nomograms could effectively predict the 1-year, 3-year and 5-year survival outcomes of patients with SMPESCs. Furthermore, adjuvant therapy has the potential to improve OS in patients with lymph node metastasis.

Background The COVID-19 pandemic raised concerns about whether individuals with chronic respiratory diseases, such as asthma, were at higher risk of severe outcomes. Although several studies were published on this topic, not all included asthma as a risk factor. Therefore, describing the clinical characteristics of COVID-19-infected asthma patients in a specialized respiratory center is valuable as a real-life study. Objective To investigate the clinical characteristics and disease severity in SARS-CoV-2-infected adults with pre-existing asthma hospitalized at the National Institute of Respiratory Diseases (INER) in Mexico City. Methods We conducted a retrospective, observational study on adults with confirmed COVID-19 hospitalized from March 2020 to June 2021. Out of 2,249 reviewed medical records, we identified asthmatic patients and compared them with a matched non-asthmatic control group to assess asthma’s impact on COVID-19 severity and outcomes. Results Based on the clinical records, asthma prevalence among hospitalized patients was low (1.51%); of these, 73% had allergic and 27% had non-allergic asthma. COVID-19 severity did not vary significantly between asthma phenotypes, although there was higher mortality among patients with non-allergic asthma. Most patients in both groups developed a severe form of the disease and higher mortality rates than non-asthmatics, though the differences were not statistically significant. Conclusion Asthma prevalence among patients with COVID-19 was low, but mortality was higher in asthma patients. Although the small sample size limits the generalizability of these findings, this study in a Mexican population hospitalized in a reference hospital provides insights for improving asthma management in future pandemics.

Introduction It is unclear whether changing trajectories of renal function will increase the risk prediction information of cardiovascular disease (CVD). This study aimed to evaluate the trajectory patterns of estimated glomerular filtration rate (eGFR) and the association between eGFR trajectories and CVD risk. Methods A total of 4742 participants were included in the cohort from the 51st Regiment of Xinjiang Production and Construction Corps. The study endpoint was the occurrence of CVD events. eGFR trajectories were identified using a linear mixed-effects model in four distinct patterns. Multivariate Cox proportional hazards models analysed the correlations between eGFR trajectories and CVD. Results During a median follow-up period of 5.7 years, a total of 559 (11.8%) CVD, 404 (8.5%) myocardial infarction (MI), 244 (5.2%) ischemic stroke (IS), and 62 (1.3%) heart failure (HF) incidents occurred. After multivariable adjustment, gradual decline trajectory increased the risk of CVD (HR 1.42, 95% CI 1.16–1.74), MI (HR 1.41, 95% CI 1.11–1.79), and IS (HR 1.41, 95% CI 1.04–1.92); gradual increase trajectory reduced the risk of CVD (HR 0.40, 95% CI 0.25–0.64) and MI (HR 0.49, 95% CI 0.29–0.81). Consistent results were obtained in sensitivity and subgroup analyses. Conclusions Decline and increase of renal function were related to the risk of CVD, MI, and IS in the rural areas of Xinjiang. Monitoring eGFR changing trajectory is of great significance in improving the risk of CVD.

Objective A pilot study to evaluate the correlation between multimodal imaging features and the expression of the human epidermal growth factor receptor type 2 (HER-2) in breast cancer to provide a basis for clinical treatment and prognosis evaluation. Methods We included a total of 62 patients with breast cancer admitted to the Affiliated Hospital of Hebei University between 2018 and 2022. All of them underwent the relevant investigations, including ultrasound, mammography, and enhanced magnetic resonance imaging (MRI), in the hospital within one month before surgery or biopsy. HER-2 expression level was divided into negative and positive by immunohistochemistry(IHC). Using SPSS 24.0 statistical software to analyze the differences in imaging features between the HER-2 positive and the HER-2 negative groups. Results There was a statistically significant difference between the HER-2 positive and the HER-2 negative groups (p = 0.005) in the hyperechoic halo sign around the lesion detected by ultrasonography as well as in the apparent diffusion coefficient (ADC) on MRI (p = 0.047). The sensitivity and specificity of the hyperechoic halo sign in predicting HER-2 positivity was 48.3% and 84.8% respectively, and the area under the curve (AUC) for the ADC value to predict HER-2 expression was 0.533. When b was equal to 800 and the ADC value (cutoff value) was 0.000888 mm²/s, the sensitivity and specificity were 65.5% and 51.5%, respectively. Conclusion A combination of multimodal imaging features and HER-2 gene expression can provide more valuable information for clinical diagnosis and therapeutic schedule in breast cancer.

Background Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease among preterm infants. Owing to the limitations in current diagnostic methods, developing a predictive model for BPD is crucial. Methods Using 243 autophagy-associated genes and dataset GSE32472, differential expression of autophagy-associated genes was identified at postnatal days 5, 14, and 28 between BPD patients and controls. LASSO and multivariate logistic regression analyses were performed to screen for diagnostic prediction genes. Receiver Operating Characteristic, Harrell’s concordance index, and decision curve analysis (DCA) were used to evaluate the diagnostic prediction model in GSE32472 and GSE220135. A BPD mouse model was constructed and qRT-PCR and Western blot were used to verify gene expression in lung tissue. Results Based on p < 0.05, we constructed a diagnostic prediction model for BPD using WIPI1, TOMM70A, BAG3, and PRKCQ. For the training database, the model’s C-index and Area under Curve were both 0.941, and a high applicability value was demonstrated by the DCA curve. These outcomes were also confirmed in the validation cohort GSE220135, demonstrating the superior diagnostic prediction capability of our approach. In addition, significant variations in immune cell infiltration were observed between BPD patients and controls. According to the results of qRT-PCR, BPD model mice had significantly lower expression levels of WIPI1, TOMM70A, BAG3, and PRKCQ than controls. Conclusions We constructed and validated a diagnostic prediction model for BPD based on WIPI1, TOMM70A, BAG3, and PRKCQ. These four genes may influence BPD development by regulating immune responses and immune cells.

Background Chinese resident physicians confront challenges such as staff shortages and heavy workloads, leading to a heightened prevalence of mental distress. This study aims to investigate the symptom network of stress, burnout, anxiety, depression (SBAD) and adverse personal outcomes in this cohort. Methods From October 2020 to April 2022, 994 physicians were recruited across China through snowball sampling. Stress, burnout, anxiety and depression were assessed using the 10-item Perceived Stress Scale, a two-item burnout questionnaire, Generalized Anxiety Disorder Scale-7 and the Patient Health Questionnaire-9, respectively. Data on adverse personal outcomes (low quality of life [QOL] and suicidal ideation) were collected. We constructed and visualized two networks, calculating expected influence (EI) and bridge EI indices to identify central and bridge symptoms. Results In the SBAD network, perceived helplessness was the most central and critical bridge symptom connecting stress and mental distress, with emotional exhaustion identified as the secondary bridge symptom. Perceived helplessness, perceived self-efficacy and emotional exhaustion exhibited the highest negative correlations with QOL. Worthless (PHQ6) and motor (PHQ8) symptoms were strongly correlated with suicidal ideation. The estimated SBAD network showed excellent stability and accuracy. Conclusions Our study emphasizes that perceived helplessness may be a high-priority target for preventing and intervening in mental distress and improving QOL among residents. Burnout transcends workplace problems and is widely connected to depression, anxiety and QOL. Implementing early detection and intervention measures at three levels—the individual physician, health system and professional colleges, and external regulators—is crucial for preventing and alleviating stress and mental distress among residents.

Diabetes mellitus is a metabolic disease that is marked by persistent hyperglycemia due to inadequate insulin secretion or insulin resistance. Its prevalence is increasing yearly. Diabetes mellitus can lead to serious health complications that are the primary cause of mortality and disability among diabetic patients, including diabetic retinopathy, diabetic foot ulcers, diabetic peripheral neuropathy, and diabetic periodontitis, and so on. Traditional treatments for diabetes and its complications still suffer from limited clinical efficacy and high therapeutic side effects. Photobiomodulation (PBM), which utilizes low levels of red or near-infrared laser to irradiate cells and tissues, has been shown to be efficacious for a wide range of organ damage. In this study, we focus on the application of PBM in diabetes and its complications and mechanisms, as well as the advantages, disadvantages with the aim of developing new ideas for the application of PBM.

Objective We aim to investigate the joint effect of triglyceride-glucose (TyG) index and polygenic risk scores (PRS) of urate transporter genes ABCG2 and SLC2A9 on hyperuricemia. Methods Baseline data from two prospective population-based cohort studies, including 30,453 individuals aged 50 years or older, were used to analyze the association between TyG index and hyperuricemia. A case-control study was then designed from the cohorts to investigate the interaction between genetic predisposition and TyG index on hyperuricemia among 595 matched pairs. PRS was constructed using 14 single nucleotide polymorphisms located in the ABCG2 and SLCA29 genes. Results In both sexes, higher TyG index levels were correlated with elevated serum urate (SUA) levels (p values in both sexes < 0.001). In men, per unit increase of TyG was associated with a 1.44-fold (95% confidence interval [CI]: 1.35–1.55) higher risk of hyperuricemia after adjusted for covariates. In women, this estimate was 1.69 (1.51–1.89). Demonstrated by the restrict cubic spline model, TyG index was both linearly and non-linearly associated with elevated SUA (both p values < 0.001). Association between TyG index and hyperuricemia was stronger among people with higher genetic risk, and vice versa. Compared to people with TyG < 9 and PRS < 2, the odds ratios (ORs) (95% CIs) for hyperuricemia in the TyG <9 but PRS ≥2, TyG ≥9 but PRS < 2, TyG ≥9 and PRS ≥2 groups were 3.30 (1.53–7.14), 3.16 (1.23–8.11) and 7.55 (2.76–20.65), respectively. Additive interaction was also significant, with 57.5% (30.5%–84.4%) of the excess risk attributable to the additive gene-TyG index interaction. Conclusions The impact of genetic predisposition on hyperuricemia was significantly greater among individuals with a higher TyG index. Over 50% of the increased risk can be attributed to the interaction, indicating a crucial synergy between genetic factors and TyG index when estimating hyperuricemia risk.

Background The high prevalence of drug-induced liver failure (DILF) have drawn great attention from clinicians. Aim To further delineate the clinical features of DILF and develop an easily applicable nomogram, based on readily-discernable clinical data, to predict transplant-free survival (TFS) at different time points. Methods 202 DILF patients were enrolled between January 2016 and December 2022, and were followed up from DILF diagnosis to death, liver transplantation, or 91 days afterward, whichever came first. The primary endpoint, though, was 21-day TFS. Clinical data was collected from all patients, and independent risk factors associated with death/liver transplantation was identified using both uni- and multi-variate Cox regression analyses. Results Independent risk factors incorporated into the predictive nomogram are neutrophils (HR = 1.148, 95% CI = 1.048–1.257), prothrombin time (HR = 1.048, 95% CI = 1.017–1.080), albumin (HR = 0.880, 95% CI = 0.823–0.941), acute kidney injury (HR = 2.487, 95% CI = 1.134–5.452), and hepatic encephalopathy (HR = 3.378, 95% CI = 1.744–6.543). The resulting nomogram was highly predictive, with an area under the curve of 0.947 for 21-day TFS. Conclusions Compared to existing models, such as the Model for End-Stage Liver Disease score, the predictive nomogram is more accurate, only requires easily-measurable clinical and laboratory metrics, as well as being able to directly calculate TFS at various time points.

Objective Although the incidence and case fatality (CF) of acute myocardial ischaemic syndrome (AMIS) have declined in recent decades, some studies have suggested a potential stagnation in this decline. We examined if a similar development in AMIS trends can be observed in Finland from 1996 to 2021 among persons aged 35–74 years. Methods We linked Finnish country-wide Hospital Discharge- and Causes of Death- Registers covering the first non-fatal and fatal myocardial ischaemic events (total 69 906 442 person-years at risk). We analyzed the incidence, mortality, and 28-day CF and their trends using negative binomial, Poisson, segmented and logistic regression adjusting for age and sex. Results The analysis consisted of 186 489 non-fatal and 72 907 fatal myocardial ischaemic events. AMIS incidence declined in men (annual percentage change (APC) −2.0%) and in older women (APC of 55–64 years −1.5%; 65–74 years −3.3%) during the study period. However, the incidence decline slowed down over the last decade in oldest age groups and stopped overall in women. Incidence was unchanged during the study period in younger women aged 35-54 years. AMIS mortality and CF declined (APC of mortality in men −4.4%; in women −5.0%; APC of CF in men −2.7%; in women −3.3%). Conclusions AMIS mortality declined in all groups, but the decline in AMIS incidence slowed down and even stopped in women. Incidence was unchanged during the study period in women aged 35-54 years. These results emphasize the need for further efforts in prevention of cardiovascular disease, particularly in young and middle-aged women.

Aims To investigate a comprehensive panel of biomarkers and risk of aortic stenosis (AS) in a prospective population-based study. Methods Anthropometric, metabolic, and inflammatory biomarkers were measured in the Metabolic Syndrome in the Men Study of 10,144 Finnish men without AS at baseline. Cases of AS were identified from the medical records. Cox regression analysis was used to identify variables predicting AS over a follow-up time of 10.8 years. Principal component (PC) analysis was applied to the biomarkers that predicted AS. Cox regression analysis was used to investigate the resulting PCs as AS predictors. Results AS was diagnosed in 116 men (1.1%), with a median age of 62 years. In Cox regression analyses, fasting, 30 min, and 120 min plasma insulin, and proinsulin, with hazard ratios (HR) ranging from 1.38 (1.12-1.69, p = 2.1E-3) to 1.44 (1.23-1.68, p = 4.0E-6), Matsuda index [HR 0.68 (0.56-0.82, p = 6.9E-5)], and serum C-peptide [HR 1.47 (1.22-1.77, p = 5.0E-5)] were associated with incident AS, in addition to age, systolic blood pressure, BMI, waist circumference, waist/hip ratio, height, body fat mass, fat-free mass, and hs-CRP, and remained significant after adjustments, or if diabetic subjects were excluded. PC 1, consisting of fasting plasma insulin, C-peptide, Matsuda index, waist/hip ratio, and urine albumin excretion, and PC 2, consisting of age, body fat mass, and systolic blood pressure, were significantly associated with AS [HRs 1.37(1.09-1.73) and 1.77 (1.45-2.17), respectively]. Conclusion Biomarkers reflecting insulin resistance are risk factors for AS, a novel finding indicating that insulin resistance is important in the pathogenesis of AS.

Background Lung adenocarcinoma is the most common type of lung cancer, accounting for approximately 40% of all lung cancer cases, and has the highest incidence among lung cancer subtypes. Recent studies have suggested that long non-coding RNAs (lncRNAs) play a crucial role in the initiation and progression of lung adenocarcinoma. Methods Based on integrative analysis through databases, we screened Long intergenic non-protein coding RNA 00839 (LINC00839) as one of the most highly upregulated lncRNAs in lung adenocarcinoma. In vitro and in vivo experiments demonstrated that LINC00839 promotes lung adenocarcinoma proliferation, migration, and invasion and that it is present in exosomes secreted by lung adenocarcinoma cells. Results In the cytoplasm, LINC00839 regulates the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway by acting as a molecular sponge of miR-17-5p, thereby influencing the biological behavior of lung adenocarcinoma cells. LINC00839 binds to Polypyrimidine tract binding protein 1 (PTBP1) in the nucleus to regulate the nuclear translocation of NF-κB p65 molecules and, consequently, the transcription of downstream molecules. Conclusions Our study confirmed that LINC00839 promotes the biological progression of lung adenocarcinoma by performing dual roles in the cytoplasm and nucleus to co-regulate the NF-κB signaling pathway.

Objectives We aim to investigate the ethical attitudes of the Chinese population toward withdrawal of life-sustaining treatment (WLST) in disorders of consciousness (DoC) patients. Methods A self-administered questionnaire concerning WLST was distributed to Chinese medical professionals and non-medical participants between February and July 2022. Statistical analysis included chi-square tests and logistic regressions. Results A total of 1223 Chinese participants responded to the questionnaire (39% of whom were medical professionals). Less than one third of participants reported positive attitudes towards withdrawing artificial nutrition and hydration (ANH), antibiotics, and do-not-resuscitation (DNR) orders in patients with unresponsive wakefulness syndrome (UWS) (30%, 24%, 24%) and minimally conscious state (MCS) (23%, 19%, 15%). More respondents agreed with WLST in UWS compared to MCS (p < 0.05). Positive attitudes toward DNR orders were associated with participants’ older age, religion, monthly income > 5000 RMB and medical profession (p < 0.05). Most participants deemed patient’s will (78%), families’ wishes (67%), and financial burden (63%) to be crucial factors when considering WLST. Conclusions Chinese respondents exhibit a relatively low propensity to accept WLST in DoC. Ethical attitudes toward WLST resulted to be affected by individual characteristics of responders. These results call for developing better regulations for identifying qualified surrogate decision-makers and reducing legal ambiguities.