Discordance between Remnant Cholesterol and Low-density Lipoprotein Cholesterol Predicts Cardiovascular Disease: the Kailuan Prospective Cohort Study.

BACKGROUND: Previous studies have shown that remnant cholesterol (RC) was associated with cardiovascular disease (CVD). The study aim to identify the association of RC and the discordance between RC and lipoprotein cholesterol (LDL-C) with CVD. METHODS: Data was obtained from the Kailuan study. RC was calculated as the non high-density lipoprotein cholesterol minus LDL-C. Discordant RC and LDL-C were defined by percentile difference and clinical cutoff points. Cox proportional hazard models were used to explore the association of RC and the discordance between RC and LDL-C with CVD. RESULTS: Total of 96,769 participants were inclued, with the median age of 51.61 years, 79.56% of male. There was a significant association between RC levels and the risk of CVD, with an HR of 1.10 (95% CI, 1.08-1.13) in the continuous analysis. The discordantly high RC group had a significant increase in CVD, MI, and stroke risk, with HRs of 1.18 (95%CI, 1.10-1.26), 1.23 (1.06-1.43), and 1.15 (1.07-1.24), respectively. Compared to the group with low LDL-C and low RC, the group with low LDL-C and high RC had significantly higher incidences of CVD (HR, 1.33 [95% CI, 1.26-1.40]), MI (HR, 1.59 [95% CI, 1.41-1.80]), and stroke (HR, 1.28 [95% CI, 1.20-1.35]). CONCLUSIONS: Elevated levels of RC and discordantly high RC with LDL-C both were associated with the risk of CVD, MI, and stroke. These findings demonstrate the clinical significance of identifying residual risk related to RC.

Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1ß.

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1ß in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1ß. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1ß, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1ß. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

Sex differences in correlates of suicide attempts in Chinese Han first-episode and drug-naïve major depressive disorder with comorbid subclinical hypothyroidism: A cross-sectional study.

BACKGROUND: This study aimed to investigate sex differences in risk factors for suicide attempts in first-episode and drug naive (FEDN) major depressive disorder (MDD) with comorbid subclinical hypothyroidism (SCH). METHODS: A total of 1034 FEDN MDD patients with comorbid SCH were enrolled. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were used to assess patients' symptoms. Thyroid hormone levels and metabolic parameters were measured. RESULTS: MDD patients with SCH had a significantly higher risk of suicide attempts than those without SCH (25.4% vs. 12.2%). Logistic regression showed that HAMA score, thyroid stimulating hormone (TSH) levels, and thyroid peroxidase antibody (TPOAb) levels were significantly associated with an increased risk for suicide attempts in both male and female MDD patients comorbid SCH, while low-density lipoprotein cholesterol (LDL-C) was significantly associated with an increased risk for suicide attempts only in male patients, HAMD score and systolic blood pressure were significantly associated with an increased risk for suicide attempts only in female patients. CONCLUSION: SCH comorbidities may increase suicide attempts in MDD patients. Our results showed significant sex differences in clinical and metabolic factors associated with suicide attempts among FEDN MDD patients with comorbid SCH, highlighting appropriate sex-based preventive interventions are needed.

Association between Adverse Psychological Emotions and Postoperative Brace for Adolescent Idiopathic Scoliosis: A Prospective Cohort Study with Propensity Score Matching.

OBJECTIVE: Although the advantages of postoperative braces have been verified in many fields, it is not clear whether postoperative braces can help reduce patients' adverse psychological emotions such as kinesiophobia, anxiety, and depression. This study aims to analyze whether the use of a postoperative brace helps reduce adverse psychological emotions in adolescent idiopathic scoliosis (AIS) patients undergoing spinal deformity surgeries. METHODS: All consecutive patients who underwent spinal corrective surgeries at our institution between April 2023 and July 2023 formed the prospective cohort. Outcome measures were collected in the preoperative period, 3 months after surgery, and 6 months after surgery. All patients were assessed using the Tampa scale for kinesiophobia (TSK), the hospital anxiety and depression scale (HADS), and the numerical rating scale (NRS). A statistical model of propensity score matching was used to eliminate potential selection bias and maintain comparability. Multivariate linear regression models were used to determine the relationship between postoperative brace and adverse psychological emotions. RESULTS: After propensity score matching, this study ultimately enrolled 150 patients. There were no significant differences between the two groups in terms of demographic and perioperative variables. The fully adjusted model showed that the TSK scores of the non-brace group at the 3-month (ꞵ = 2.50, 95% CI 0.80-4.20, p = 0.005) and 6-month follow-up (ꞵ = 2.75, 95% CI 0.75-4.74, p = 0.007) were significantly higher than those of the brace group. The HADS score of the non-brace group at the 3-month follow-up was significantly higher than that of the brace group (ꞵ = 1.75, 95% CI 0.28-3.22, p = 0.019). The NRS score of the non-brace group at the 3-month follow-up was significantly higher than that of the brace group (ꞵ = 0.69, 95% CI 0.05-1.33, p = 0.034). At the 6-month follow-up, there were no significant difference for HADS score or NRS score between the two groups. CONCLUSION: In the early postoperative period, the postoperative brace could provide AIS patients with psychological supports and help them reduce the frequency of adverse psychological emotions. The postoperative brace could continuously improve the fear of movement within 6 months after surgery, and help reduce anxiety, depression, and pain within 3 months after surgery.

Greater variability in HDL-C was associated with an increased risk of cognitive decline in the middle- and elderly Chinese: A cohort study.

BACKGROUND: Previous studies into relationship between high-density lipoprotein cholesterol (HDL-C) and cognitive decline were constrained to a single measurement, leaving the association between HDL-C variability and risk of cognitive decline unclear. METHODS: We identified 5930 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were devoid for stroke, dementia, and memory-related diseases at baseline and underwent a minimum of 2 sequential health examinations during 2011-2015. Variability in HDL-C was defined as (1) variability independent of the mean (VIM), (2) average real variability (ARV), and (3) standard deviation (SD) of HDL-C change from baseline and follow-up visits. Cognitive function was evaluated in 2018 by Mini-mental state examination (MMSE) in the Chinese version. Logistic regression was employed to explore the association between HDL-C variability and cognitive decline. Odd ratios (OR) and 95 % confidence intervals (CI) were reported. RESULTS: The study included participants from CHARLS, mean age of 57.84±8.44 years and 44 % male. After adjustment for covariates, the highest quartile of VIM was associated with an increased risk of cognitive decline [OR:1.049, 95 %CI: 1.014-1.086] compared to the lowest quartile. For each SD increment of VIM, the OR was 1.015 (95 %CI:1.003-1.027). Strong dose-response relationships were identified (P for trend: 0.005). Consistent results were obtained for other measures of HDL-C variability (ARV and SD). Similar patterns were identified in different dimensions of cognition. CONCLUSIONS: Elevated HDL-C variability was associated with increased cognitive decline risk. Strategies to reducing HDL-C variability may lower the risks of cognitive decline among the general population.

[Association between exposure to PM_(2.5) and chronic kidney disease in a population with metabolic syndrome].

OBJECTIVE: To investigate the association between long-term fine particulate matter(PM_(2.5)) exposure and the risk of chronic kidney disease(CKD) in people with abnormal metabolism syndrome(MS) components. METHODS: Based on health checkup data from a hospital in Beijing, a retrospective cohort study was used to collect annual checkup data from 2013-2019. A questionnaire was used to obtain information on demographic characteristics and lifestyle habits. We measured blood pressure, height, weight, waist circumference, concentrations of triglycerides(TG), fasting glucose, and high-density lipoprotein cholesterol(HDL-C). Longitude and latitude were also extracted from the addresses of the study subjects for pollutant exposure data estimation. Logistic regression models were used to explore the estimated effect of long-term PM_(2.5) exposure on the risk of CKD prevalence in people with abnormal MS components. Two-pollutant and multi-pollutant models were developed to test the stability of these result. Subgroup analysis was conducted based on age, the presence of MS, individual MS component abnormalities, and dual-component MS abnormalities. RESULTS: The study included 1540 study subjects with abnormal MS components at baseline, 206 with CKD during the study period. The association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions was statistically significant, with a 2.26-fold increase in risk of CKD for every 10 µg/m~3 increase in PM_(2.5) exposure(OR=3.26, 95% CI 2.72-3.90). The result in the dual-pollutant models and multi-pollutant models suggested that the association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions remained stable after controlling for contemporaneous confounding by other air pollutants. The result of subgroup analysis revealed that individuals aged 45 or older, without MS, with TG<1.7 mmol/L, HDL-C≥1.04 mmol/L, without hypertension, and with central obesity and high blood sugar had a stronger association between PM_(2.5) exposure and CKD-related health effects. CONCLUSION: Long-term exposure to PM_(2.5) may increase the risk of CKD in people with abnormal MS components. More attention should be paid to middle-aged and elderly people aged ≥45 years, people with central obesity and hyperglycemia.

Ame-miR-1-3p of bee venom reduced cell viability through the AZIN1/OAZ1-ODC1-polyamines pathway and enhanced the defense ability of honeybee (Apis mellifera L.).

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.

Systolic blood pressure and risk of cardiovascular disease in normotensive diabetic adults: a prospective cohort study.

BACKGROUND: Currently, the special blood pressure (BP) target for normotensive diabetic patients has not been recommended. We investigated the optimal systolic blood pressure (SBP) for lower cardiovascular disease (CVD) risk in normotensive diabetic patients. METHODS: In this 12-year follow-up study using the participants of the Kailuan Study, we mainly compared which SBP, 90-119 mmHg or 120-129 mmHg, had a lower risk of occurrence of CVD (stroke and myocardial infarction) in the 3072 normotensive diabetic participants and 21,532 normotensive and non-diabetic participants, respectively. The SBP was expressed as a mean time-weighted cumulative (MTWC) SBP, calculated from the multiple measurements of SBP during the follow-up. Multivariate competing risk regression analyses were used for the analysis. RESULTS: We found that in normotensive diabetic participants, MTWC SBP of 120-129 mmHg was associated with a lower risk of CVD (HR = 0.69 [0.50-0.95]), myocardial infarction (HR = 0.48 [0.24-0.96]), and trending towards lower risk of stroke (HR = 0.80 [0.55-1.16]), compared to MTWC SBP of 90-119 mmHg. Sensitivity analyses confirmed the relationship between low SBP and increased CVD risk. Whereas, in the normotensive and non-diabetic participants, MTWC SBP of 90-119 mmHg vs 120-129 mmHg did not exhibit any difference in the risk of CVD occurrence (HR = 0.99 [0.83-1.18]). CONCLUSIONS: The higher level of SBP in normotensive diabetic patients is especially associated with a lower risk of CVD occurrence.

Image fusion-based low-dose CBCT enhancement method for visualizing miniscrew insertion in the infrazygomatic crest.

Digital dental technology covers oral cone-beam computed tomography (CBCT) image processing and low-dose CBCT dental applications. A low-dose CBCT image enhancement method based on image fusion is proposed to address the need for subzygomatic small screw insertion. Specifically, firstly, a sharpening correction module is proposed, where the CBCT image is sharpened to compensate for the loss of details in the underexposed/over-exposed region. Secondly, a visibility restoration module based on type II fuzzy sets is designed, and a contrast enhancement module using curve transformation is designed. In addition to this, we propose a perceptual fusion module that fuses visibility and contrast of oral CBCT images. As a result, the problems of overexposure/underexposure, low visibility, and low contrast that occur in oral CBCT images can be effectively addressed with consistent interpretability. The proposed algorithm was analyzed in comparison experiments with a variety of algorithms, as well as ablation experiments. After analysis, compared with advanced enhancement algorithms, this algorithm achieved excellent results in low-dose CBCT enhancement and effective observation of subzygomatic small screw implantation. Compared with the best performing method, the evaluation metric is 0.07-2 higher on both datasets. The project can be found at: https://github.com/sunpeipei2024/low-dose-CBCT .

Rosmarinic acid alleviates fungal keratitis caused by Aspergillus fumigatus by inducing macrophage autophagy.

Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1ß, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.

Cumulative remnant cholesterol burden increases the risk of cardiovascular disease among young adults.

BACKGROUND: Previous studies have shown that remnant cholesterol (RC) was associated with cardiovascular disease (CVD) among middle-aged or older adults. However, lack of evidence on long-term exposures to RC and their role in CVD risk among young adults. We thus aimed to explore the association between cumulative RC burden and CVD in young adults. METHODS: We enrolled participants younger than 45 years free of CVD history in the Kailuan Study who completed the first three health examinations from 2006 to 2010. Cumulative RC burden included cumulative RC burden score, time-weighted cumulative RC, exposure duration of high RC, and time course of RC accumulation. The outcome was the incidence of CVD. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) between cumulative RC burden and CVD risk. RESULTS: A total of 15,219 participants were included (73.70% male, median age 39.13 years). During a median follow-up duration of 8.71 years (interquartile range: 8.4-9.15 years), 502 individuals developed CVD. After adjustment for traditional cardiovascular risk factors, highest risk of CVD was observed in participants with the highest cumulative RC burden score (HR, 1.66; 95% CI, 1.29-2.12), the highest quartile time-weighted cumulative RC (HR,1.50; 95% CI, 1.15-1.96), the longest exposure duration of high RC (HR, 1.71; 95% CI, 1.21-2.42), and those with cumulative RC burden and positive slope (HR, 1.79; 95% CI, 1.35-2.36). CONCLUSIONS: Cumulative RC burden increased the risk of CVD among young adults, suggesting that maintaining low RC levels throughout young adulthood may minimize CVD risk.

Minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori (H. pylori) infection, but the systematic evaluation of its role remains lacking. AIM: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection. METHODS: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured. RESULTS: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%). CONCLUSION: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection.

Chemical Constituents and Pharmacological Properties of Frankincense: Implications for Anticancer Therapy.

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.

Ebselen improves fungal keratitis through exerting anti-inflammation, anti-oxidative stress, and antifungal effects.

Fungal keratitis is a severely vision-threatening corneal infection, where the prognosis depends on both fungal virulence and host immune defense. Inappropriate host responses can induce substantial inflammatory damage to the cornea. Therefore, in the treatment of fungal keratitis, it is important to concurrently regulate the immune response while efforts are made to eliminate the pathogen. Ebselen is a widely studied organo-selenium compound and has been demonstrated to have antifungal, antibacterial, anti-inflammatory, and oxidative stress-regulatory properties. The effectiveness of ebselen for the treatment of fungal keratitis remains unknown. In this study, ebselen was demonstrated to produce a marked inhibitory effect on Aspergillus fumigatus (A. fumigatus), including spore germination inhibition, mycelial growth reduction, and fungal biofilm disruption. The antifungal activity of ebselen was related to the cell membrane damage caused by thioredoxin (Trx) system inhibition-mediated oxidative stress. On the contrary, ebselen enhanced the antioxidation of Trx system in mammalian cells. Further, ebselen was proven to suppress the expressions of inflammatory mediators (IL-1ß, IL-6, TNF-α, COX-2, iNOS, and CCL2) and reduce the production of oxidative stress-associated indicators (ROS, NO, and MDA) in fungi-stimulated RAW264.7 cells. In addition, ebselen regulated PI3K/Akt/Nrf2 and p38 MAPK signaling pathways, which contributed to the improvement of inflammation and oxidative stress. Finally, we verified the therapeutic effect of ebselen on mouse fungal keratitis. Ebselen improved the prognosis and reduced the fungal burden in mouse corneas. Expressions of inflammatory mediators, as well as the infiltration of macrophages and neutrophils in the cornea were also obviously decreased by ebselen. In summary, ebselen exerted therapeutic effects by reducing fungal load and protecting host tissues in fungal keratitis, making it a promising treatment for fungal infections.

Neural correlates of individual differences in moral identity and its positive moral function.

Moral identity is an important moral variable which has positive moral functions, such as contributing to prosocial behaviours, reducing antisocial behaviours, and resisting the risk factors of antisocial behaviours. However, little is known about the neural correlates of moral identity and the neural basis of the effect of moral identity on the risk factors of antisocial behaviours, including moral disengagement. In this study, we explored these issues in 142 college students by estimating the regional homogeneity (ReHo) through resting-state functional magnetic resonance imaging (fMRI). The whole-brain correlation analyses found that higher internalized moral identity was correlated with higher ReHo in the precuneus. Furthermore, the ReHo in the precuneus was negatively correlated with moral disengagement, suggesting positive moral functions of the neural mechanisms of moral identity. These findings deepen our understanding of individual differences in moral identity and provide inspiration for the education of moral identity and the intervention for moral disengagement from the perspective of the brain.

Mediating role of social support in dysphoria, despondency, and quality of life in patients undergoing maintenance hemodialysis.

BACKGROUND: Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis (MHD) that significantly affect their quality of life (QOL). High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD. Currently, there is limited research on how social support mediates the relationship between dysphoria, despondency, and overall QOL in patients undergoing MHD. It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD, ultimately enhancing their overall QOL. AIM: To investigate the mediating role of social support in relationships between dysphoria, despondency, and QOL among patients undergoing MHD. METHODS: Participants comprised 289 patients undergoing MHD, who were selected using a random sampling approach. The Social Support Rating Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and QOL Scale were administered. Correlation analysis was performed to examine the associations between social support, dysphoria, despondency, and QOL in patients undergoing MHD. To assess the mediating impact of social support on dysphoria, despondency, and QOL in patients undergoing MHD, a bootstrap method was applied. RESULTS: Significant correlations among social support, dysphoria, despondency, and quality in patients undergoing MHD were observed (all P < 0.01). Dysphoria and despondency negatively correlated with social support and QOL (P < 0.01). Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD (P < 0.05). The direct effect of dysphoria on QOL was statistically significant (P < 0.05). Social support mediated the relationship between dysphoria and QOL, and this mediating effect was significant (P < 0.05). Similarly, the direct effect of despondency on QOL was significant (P < 0.05). Moreover, social support played a mediating role between despondency and QOL, with a significant mediating effect (P < 0.05). CONCLUSION: These findings suggest that social support plays a significant mediating role in the relationship between dysphoria, despondency, and QOL in patients undergoing MHD.

Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway.

OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS: Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

Rehabilitation with brain-computer interface and upper limb motor function in ischemic stroke: A randomized controlled trial.

BACKGROUND: Upper limb motor dysfunction is a major problem in the rehabilitation of patients with stroke. Brain-computer interface (BCI) is a kind of communication system that converts the "ideas" in the brain into instructions and has been used in stroke rehabilitation. This study aimed to investigate the efficacy and safety of BCI in rehabilitation training on upper limb motor function among patients with ischemic stroke. METHODS: This was an investigator-initiated, multicenter, randomized, open-label, blank-controlled clinical trial with blinded outcome assessment conducted at 17 centers in China. Patients were assigned in a 1:1 ratio to the BCI group or the control group based on traditional rehabilitation training. The primary efficacy outcome is the difference in improvement of the Fugl-Meyer Assessment upper extremity (FMA-UE) score between two groups at month 1 after randomization. The safety outcomes were any adverse events within 3 months. FINDINGS: A total of 296 patients with ischemic stroke were enrolled and randomly allocated to the BCI group (n = 150) and the control group (n = 146). The primary efficacy outcomes of FMA-UE score change from baseline to 1 month were 13.17 (95% confidence interval [CI], 11.56-14.79) in the BCI group and 9.83 (95% CI, 8.19-11.47) in the control group (mean difference between groups was 3.35; 95% CI, 1.05-5.65; p = 0.0045). Adverse events occurred in 33 patients (22.00%) in the BCI group and in 31 patients (21.23%) in the control group. CONCLUSIONS: BCI rehabilitation training can further improve upper limb motor function based on traditional rehabilitation training in patients with ischemic stroke. This study was registered at ClinicalTrials.gov: NCT04387474. FUNDING: This work was supported by the National Key R&D Program of China (2018YFC1312903), the National Key Research and Development Program of China (2022YFC3600600), the Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2022ZKYXZ009), the Beijing Natural Science Foundation Haidian original innovation joint fund (L222123), the Fund for Young Talents of Beijing Medical Management Center (QML20230505), and the high-level public health talents (xuekegugan-02-47).

Construction of a New Agrobacterium tumefaciens-Mediated Transformation System based on a Dual Auxotrophic Approach in Cordyceps militaris.

Cordyceps militaris is a significant edible fungus that produces a variety of bioactive compounds. We have previously established a uridine/uracil auxotrophic mutant and a corresponding Agrobacterium tumefaciens-mediated transformation (ATMT) system for genetic characterization in C. militaris using pyrG as a screening marker. In this study, we constructed an ATMT system based on a dual pyrG and hisB auxotrophic mutant of C. militaris. Using the uridine/uracil auxotrophic mutant as the background and pyrG as a selection marker, the hisB gene encoding imidazole glycerophosphate dehydratase, required for histidine biosynthesis, was knocked out by homologous recombination to construct a histidine auxotrophic C. militaris mutant. Then, pyrG in the histidine auxotrophic mutant was deleted to construct a ΔpyrG ΔhisB dual auxotrophic mutant. Further, we established an ATMT transformation system based on the dual auxotrophic C. militaris by using GFP and DsRed as reporter genes. Finally, to demonstrate the application of this dual transformation system for studies of gene function, knock out and complementation of the photoreceptor gene CmWC-1 in the dual auxotrophic C. militaris were performed. The newly constructed ATMT system with histidine and uridine/uracil auxotrophic markers provides a promising tool for genetic modifications in the medicinal fungus C. militaris.

Association between peripheral plasma cytokine levels and suicidal ideation in first-episode, drug-naïve major depressive disorder.

BACKGROUND: Inflammatory processes could potentially impact both mood and suicide risk, however, the relationship between cytokines and suicidal ideation remains unclear. This study aimed to investigate the association between plasma levels of cytokines and suicidal ideation in population with major depressive disorders (MDD). METHODS: A cross-sectional study was performed to assess the peripheral plasma levels of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in 88 Chinese Han first-episode drug-naïve MDD patients. Suicidal ideation in the past week were identified using the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV). The Hamilton Depression Rating Scale-17 (HAMD-17), the Hamilton Anxiety Rating Scale-14 (HAMA-14) and the Childhood Trauma Questionnaire (CTQ) was used to assess depression, anxiety and childhood trauma. Multivariable logistic regression models were used to estimate the association between cytokines and suicidal ideation. Interaction and stratified analyses were conducted according to age, sex, marital status, education, smoking status, BMI and physical activity. RESULTS: Among the 88 participants, 42 individuals (47.7%) reported suicidal ideation within the past week. In the fully adjusted model, a statistically significant trend was observed in the association between IL-2 level and suicidal ideation (OR: 1.40, 95% CI: 1.00-1.97). The stratified analysis showed a statistically significant association between IL-6 level and suicidal ideation among younger people (OR: 1.17, 95% CI: 1.01-1.36) and a significant positive association between IL-8 (OR: 1.59, 95% CI: 1.03-2.44) and IL-10 (OR: 2.51, 95% CI: 1.27-4.96) levels and suicide ideation among higher educated populations. LIMITATIONS: The cross-sectional design, residual confounding effects and small sample size CONCLUSION: Our findings indicate a significant positive association between plasma IL-2 level and suicidal ideation in MDD patients. IL-2 has the potential to be a biomarker of suicidal ideation in patients with depression.