Oncolytic Newcastle disease virus carrying the IL24 gene exerts antitumor effects by inhibiting tumor growth and vascular sprouting.

The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.

Effect of Self-developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction Combined with Tramadol on TCM Symptom Scores and RLS Severity of patients with Restless Legs Syndrome.

Objective: To investigate the effect of self-developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction on Traditional Chinese Medicine (TCM) symptom scores and RLS Severity of patients with restless legs syndrome (RLS). Methods: This was a clinical comparative study. Eighty patients with RLS admitted to Baoding No.1 Central Hospital from January 2022 to December 2022 were randomly divided into observation group and control group(n=40). Patients in the control group were given basic and oral tramadol treatment, while those in the observation group were given self-developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction based on the treatment in the control group. The differences of TCM symptom scores, RLS severity (IRLS), quality of life (QOL-RLS), sleep quality (PSQI) and clinical efficacy between the two groups were compared. Results: Before treatment, no statistically significant differences were observed in the TCM symptom scores, IRLS scores, QOL-RLS scores and PSQI scores between the two groups (p>0.05). After treatment, the above scores decreased significantly in both groups, with a higher degree of decrease in the observation group than in the control group, indicating statistically significant differences (p<0.05). The QOL-RLS scores were significantly higher in the observation group than in the control group, with a statistically significant difference (p<0.05). The overall response rate in the observation group was 95.00%, which was higher than that in the control group (80.00%), with a statistically significant difference (p<0.05). Conclusion: Self-developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction leads to numerous benefits in the treatment of RLS, such as obviously ameliorating patients' clinical symptoms, reducing RLS severity, and improving their quality of life and sleep quality.

Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.

BACKGROUND: The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well-tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin-induced heart failure. METHODS AND RESULTS: Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

Surgical treatment and reproductive outcomes in caesarean scar pregnancy at a single center.

BACKGROUND: To investigate factors associated with different reproductive outcomes in patients with Caesarean scar pregnancies (CSPs). METHODS: Between May 2017 and July 2022, 549 patients underwent ultrasound-guided uterine aspiration and laparoscopic scar repair at the Gynaecology Department of Hubei Maternal and Child Health Hospital. Ultrasound-guided uterine aspiration was performed in patients with type I and II CSPs, and laparoscopic scar repair was performed in patients with type III CSP. The reproductive outcomes of 100 patients with fertility needs were followed up and compared between the groups. RESULTS: Of 100 patients, 43% had live births (43/100), 19% had abortions (19/100), 38% had secondary infertility (38/100), 15% had recurrent CSPs (RCSPs) (15/100). The reproductive outcomes of patients with CSPs after surgical treatment were not correlated with age, body mass index, time of gestation, yields, abortions, Caesarean sections, length of hospital stay, weeks of menopause during treatment, maximum diameter of the gestational sac, thickness of the remaining muscle layer of the uterine scar, type of CSP, surgical method, uterine artery embolisation during treatment, major bleeding, or presence of uterine adhesions after surgery. Abortion after treatment was the only risk factor affecting RCSPs (odds ratio 11.25, 95% confidence interval, 3.302-38.325; P < 0.01) and it had a certain predictive value for RCSP occurrence (area under the curve, 0.741). CONCLUSIONS: The recurrence probability of CSPs was low, and women with childbearing intentions after CSPs should be encouraged to become pregnant again. Abortion after CSP is a risk factor for RCSP. No significant difference in reproductive outcomes was observed between the patients who underwent ultrasound-guided uterine aspiration and those who underwent laparoscopic scar repair for CSP.

Neuroticism polygenic risk predicts conversion from mild cognitive impairment to Alzheimer's disease by impairing inferior parietal surface area.

The high prevalence of conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) makes early prevention of AD extremely critical. Neuroticism, a heritable personality trait associated with mental health, has been considered a risk factor for conversion from aMCI to AD. However, whether the neuroticism genetic risk could predict the conversion of aMCI and its underlying neural mechanisms is unclear. Neuroticism polygenic risk score (N-PRS) was calculated in 278 aMCI patients with qualified genomic and neuroimaging data from ADNI. After 1-year follow-up, N-PRS in patients of aMCI-converted group was significantly greater than those in aMCI-stable group. Logistic and Cox survival regression revealed that N-PRS could significantly predict the early-stage conversion risk from aMCI to AD. These results were well replicated in an internal dataset and an independent external dataset of 933 aMCI patients from the UK Biobank. One sample Mendelian randomization analyses confirmed a potentially causal association from higher N-PRS to lower inferior parietal surface area to higher conversion risk of aMCI patients. These analyses indicated that neuroticism genetic risk may increase the conversion risk from aMCI to AD by impairing the inferior parietal structure.

Small Left Ventricle in Patients With Atrial Fibrillation Is Associated With Increased Cardiovascular Risk.

BACKGROUND: It is still unclear whether small left ventricle (LV) is an adverse structural prognostic feature in patients with atrial fibrillation (AF). OBJECTIVES: The purpose of this study was to evaluate the association between small LV and risk of cardiovascular events in AF population. METHODS: From the China-AF registry, 7,764 patients with AF were enrolled and divided into groups with normal, small, and large LV size based on left ventricular end-diastolic dimension (LVEDD) measurement per the American Society of Echocardiography references. Cox models were used to assess the association between LV size or LVEDD with composite cardiovascular events (cardiovascular death, ischemic stroke or systemic embolism, or major bleeding). RESULTS: There were 308 (4.0%) participants assessed with small LV who were older, with lower body mass and blood pressure, and fewer comorbidities, and 429 (5.5%) were identified with large LV. Compared with the normal LV group, small LV and large LV were significantly associated with higher incidence of composite cardiovascular events (adjusted HR [aHR]: 1.54 [95% CI: 1.07-2.20] for small LV; aHR: 1.36 [95% CI: 1.02-1.81] for large LV) and cardiovascular death (aHR: 1.94 [95% CI: 1.14-3.28] for small LV; aHR: 1.83 [95% CI: 1.24-2.69] for large LV). Small LV was also associated with increased risk of major bleeding [aHR: 2.21 [95% CI: 1.01-4.86]). A U-shaped relationship between LVEDD and composite cardiovascular events was identified (Pnonlinear < 0.001). CONCLUSIONS: In a prospective AF cohort, small LV was independently associated with an increased risk of cardiovascular events, which needed consideration in risk stratification and management for patients with AF. (ChiCTR-OCH-13003729).

TES and SLC40A1 as potential biomarkers for predicting survival in T-cell acute lymphoblastic leukemia.

BACKGROUND: Identifying patients with high-risk T-cell acute lymphoblastic leukemia (T-ALL) is crucial for personalized therapy, however, the lack of robust biomarkers hinders prognosis assessment. To address this issue, our study aimed to screen and validate genes whose expression may serve as predictive indicators of outcomes in T-ALL patients, while also investigating the underlying molecular mechanisms. METHODS: Differentially expressed genes (DEGs) between T-ALL patients and healthy controls were identified by integrating data from three independent public datasets. Functional annotation of these DEGs and protein-protein interaction were also conducted. Further, we enrolled a prospective cohort of T-ALL patients (n=20) at our center, conducting RNA-seq analysis on their bone marrow samples. Survival-based Univariate Cox Analysis was employed to identify gene expressions related to survival, and an intersection algorithm was sequentially applied. Furthermore, we validated the identified genes using cases from the Therapeutically Applicable Research to Generate Effective Treatments database, plotting Kaplan-Meier curves for secondary validation. RESULTS: Through the integration of survival-related genes with DEGs identified in T-ALL, our analysis revealed six T-ALL-specific genes, the expression levels of which were linked to prognostic value. Notably, the independent prognostic value of SLC40A1 and TES expression levels was confirmed in both an external cohort and a prospective cohort at our center. CONCLUSIONS: In summary, our preliminary study indicates that the expression levels of TES and SLC40A1 genes show promise as potential indicators for predicting survival outcomes in T-ALL patients.

Comparative Efficacy of Micro-Needle-Knife Therapy and Acupuncture in Acute Ankle Sprains: A Randomized Controlled Trial.

BACKGROUND Micro-needle knife (MNK) therapy releases the superficial fascia to alleviate pain and improve joint function in patients with acute ankle sprains (AAS). We aimed to evaluate the efficacy and safety of MNK therapy vs that of acupuncture. MATERIAL AND METHODS This blinded assessor, randomized controlled trial allocated 80 patients with AAS to 2 parallel groups in a 1: 1 ratio. The experimental group received MNK therapy; the control group underwent conventional acupuncture treatment at specified acupoints. Clinical efficacy differences between the 2 groups before (time-point 1 [TP1]) and after treatment (TP2) were evaluated using the visual analogue scale (VAS) and Kofoed ankle score. Safety records and evaluations of adverse events were documented. One-month follow-up after treatment (TP3) was conducted to assess the intervention scheme's reliability. RESULTS VAS and Kofoed ankle scores significantly improved in both groups. No patients dropped due to adverse events. At TP1, there were no significant differences between the 2 groups in terms of VAS and Kofoed scores (P>0.05). However, at TP2, efficacy of MNK therapy in releasing the superficial fascia was significantly superior to that of acupuncture treatment (P<0.001). At TP3, no significant differences in scores existed between the groups (P>0.05). CONCLUSIONS This study demonstrates that 6 sessions of MNK therapy to release the superficial fascia safely and effectively alleviated pain and enhanced ankle joint function in patients with AAS, surpassing the efficacy of conventional acupuncture treatment. Future studies should increase the sample size and introduce additional control groups to further validate the superior clinical efficacy of this intervention.

Association between blood pressure variability and risk of kidney function decline in hypertensive patients without chronic kidney disease: a post hoc analysis of Systolic Blood Pressure Intervention Trial study.

BACKGROUND: Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD. METHODS: A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria. RESULTS: A total of 5700 patients were included, with a mean age of 66.4 years old. During a median of 3.29 years follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria ( P  > 0.05). CONCLUSION: This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups. REGISTRATION: URL: https://clinicaltrials.gov/ , Unique identifier: NCT01206062.

Inhibition of lysosomal TRPML1 channel eliminates breast cancer stem cells by triggering ferroptosis.

Cancer stem cells (CSCs) are a sub-population of cells possessing high tumorigenic potential, which contribute to therapeutic resistance, metastasis and recurrence. Eradication of CSCs is widely recognized as a crucial factor in improving patient prognosis, yet the effective targeting of these cells remains a major challenge. Here, we show that the lysosomal cation channel TRPML1 represents a promising target for CSCs. TRPML1 is highly expressed in breast cancer cells and exhibits sensitivity to salinomycin, a drug known to selectively eliminate CSCs. Pharmacological inhibition and genetic depletion of TRPML1 promote ferroptosis in breast CSCs, reduce their stemness, and enhance the sensitivity of breast cancer cells to chemotherapy drug doxorubicin. The inhibition and knockout of TRPML1 also demonstrate significant suppression of tumor formation and growth in the mouse xenograft model. These findings suggest that targeting TRPML1 to eliminate CSCs may be an effective strategy for the treatment of breast cancer.

Model of micro-metastases of breast cancer cells in ovarian tissue: Cryopreservation of ZR-75-1 and MDA-MB-231 cells with increased speed of warming increases malignancy.

In medicine, ovarian tissue cryopreservation exists for fertility preservation of cancer patients. In fact, ovarian tissue frozen for subsequent thawing and re-transplantation can be contaminated with cancer cells. Therefore, investigations on the effect of cryopreservation on the post-thawed viability of such cells are relevant. Speed of warming is a key parameter of cell cryopreservation. However, the data about comparative viability of cancer cells cryopreserved with different parameters of warming are limited. The aim of our investigations was to assess the malignancy of cryopreserved cancer cells after conventional cooling followed by relatively slow and quick speed of warming. In vitro cultured breast cancer cells of lines ZR-75-1 and MD0MD-231 in form of compacted fragments (as a model of solid tumors) were frozen following a protocol usually used for freezing of ovarian tissue (6 % ethylene glycol+6 % glycerol+0.15 M sucrose, -0.3 °C/min). Cells were warmed by two routine regimes of warming: at 37 °C ("slow" warming) and 100 °C ("quick" warming). Biological properties of cells were investigated: viability, proliferation rate, 2D- and 3D-migration, transmembrane movement and invasion. Quick warming at 100 °C in comparison with slow warming at 37 °C exhibited significantly higher cell survival for MDA-MB-231 cells: 70.1 % vs. 63.2 % and for ZR-75-1 86.8 % vs. 82.9 %, respectively. The cell motility including 2D movement and 3D transmembrane migration were higher after quick thawing at 100 °C. Invasive abilities of cells after cryopreservation were higher than that of fresh (non-treated cells). Both thawing regimes showed a similar rate of cell proliferation. Cryopreservation procedures, and especially this one with quick thawing, increase malignancy of ZR-75-1 and MDA-MB-231 breast cancer cells and risk of metastasis.

The ameliorative mechanism of Lactiplantibacillus plantarum NJAU-01 against D-galactose induced oxidative stress: a hepatic proteomics and gut microbiota analysis.

Probiotic intervention is an effective strategy to alleviate oxidative stress-related diseases. Our previous studies found that Lactiplantibacillus plantarum NJAU-01 (NJAU-01) exhibited antioxidant effects in a D-galactose (D-gal)-induced aging mouse model. However, the underlying mechanism remains to be unveiled. This study was aimed to investigate the ameliorative effect and mechanism of NJAU-01 against oxidative stress induced by D-gal. The results showed that NJAU-01 could reverse the tendency of a slow body weight gain induced by D-gal. NJAU-01 relieved hepatic oxidative stress via increasing the hepatic total antioxidant capacity and antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Moreover, the malondialdehyde (MDA) level was reversed after NJAU-01 supplementation. The proteomic results showed that there were 201 differentially expressed proteins (DEPs) between NJAU-01 and D-gal groups. NJAU-01 regulated the expressions of glutathione S-transferase Mu 5 (Gstm5), glutathione S-transferase P2 (Gstp2) and NADH dehydrogenase 1α subcomplex subunit 7 (Ndufa7) related to oxidative stress, and autophagy protein 5 (Atg5) and plasma alpha-L-fucosidase (Fuca2) involved in autophagy, etc. 16S rDNA sequencing results showed that NJAU-01 supplementation could regulate the gut microbiota dysbiosis induced by D-gal via increasing the relative abundances of the phylum Firmicutes and the genus Lactobacillus and reducing the relative abundances of the phylum Bacteroidetes and the genera Lachnospiraceae_NK4A136_group as well as Prevotellaceae_UCG-001, etc.. Spearman correlation analysis results showed that the altered gut microbiota composition had a significant correlation with antioxidant enzyme activities and the DEPs related to oxidative stress. Overall, NJAU-01 alleviated hepatic oxidative stress induced by D-gal via manipulating the gut microbiota composition and hepatic protein expression profile.

Prognostic Value of Inflammatory Cytokines in Predicting Hospital Readmissions in Heart Failure with Preserved Ejection Fraction.

Purpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF). Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor. Results: The levels of IL-1ß, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1ß, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission. Conclusion: Inflammatory markers, including IL-1ß, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.

Sedimentary Paleoenvironment and Organic Matter Enrichment Characteristics of Lacustrine Shahezi Shale in Songliao Basin: Insights from the Continental Scientific Drilling.

The lacustrine shale of the Shahezi Formation in the Songliao Basin has obvious organic matter enrichment characteristics and great potential for oil and gas resources. At present, the understanding of the sedimentary paleoenvironment and organic matter enrichment characteristics of the lacustrine shale of the Shahezi Formation is relatively weak. Therefore, taking the international continental scientific drilling Program (ICDP) borehole Songke-2 (SK-2) with continuous and whole Shahezi cores as the research object, combined with organic geochemistry, elemental geochemistry, and logging data, the sedimentary paleoenvironment and organic matter enrichment mechanism were studied. The results show that the organic matter of Shahezi shale is generally in the high to over mature stage. The kerogen type of organic matter is mainly II2-III. The organic matter is mainly derived from the lake basin's own algae and terrestrial higher plants. The total organic carbon (TOC) content of Shahezi shale is relatively high, and the TOC is mainly distributed between 1% and 2%. The Shahezi Formation is dominated by clay shale and siliceous shale, and experienced moderate chemical weathering during deposition. According to the analysis of organic geochemistry and elemental geochemistry data, the paleoenvironment of organic matter deposition in Shahezi shale was dominated by warm and humid climate in the early stage, and then experienced multiple cooling and arid periods. The climate type turned to semihumid-semiarid, with stable terrigenous debris input, low deposition rate, brackish water salinity and oxygen-rich-oxygen-poor water environment. The sedimentary period of Shahezi Formation is in the Cretaceous oceanic anoxic Aptian-Albian stage. During the oceanic anoxic event, the anoxic sedimentary environment and the frequent volcanic activity have an important impact on the organic matter enrichment. The oceanic anoxic event and volcanic activity are the main causes of water body hypoxia in the lake basin. The nutrients brought by volcanic activity are also one of the reasons for promoting the growth of lake basin organisms, creating good conditions for organic matter enrichment. The enrichment of organic matter in Shahezi Formation is the result of the interaction and coupling of various factors such as paleoclimate, paleoenvironment, paleoproductivity, water environment, terrestrial input, and major geological events. And, the organic matter enrichment model of Shahezi Formation shale is established.

Oridonin, a small molecule inhibitor of cancer stem cell with potent cytotoxicity and differentiation potential.

Cancer stem cells (CSCs) drive malignant tumor progression, recurrence, and metastasis with unique characteristics, including self-renewal and resistance to conventional treatments. Conventional differentiation inducers, although promising, have limited cytotoxicity and may inadvertently enhance CSC stemness. To address these challenges, ongoing efforts are dedicated to developing strategies that can effectively combine both cytotoxicity and differentiation-inducing effects. In this study, we introduce oridonin (Ori), a small molecule with dual differentiation-inducing and cytotoxicity properties capable of eliminating tumor CSCs. We isolated CSCs in B16F10 cells using the Hoechst side population method and assessed the differentiation effect of Ori. Ori's differentiation-inducing effect was further evaluated using human acute promyelocytic leukemia. The cytotoxic potential of Ori against MCF-7 and B16F10 cell lines was assessed through various methods. In vivo anti-tumor and anti-CSC efficacy of Ori was investigated using mouse melanoma and CSCs melanoma models. Safety evaluation included zebrafish embryotoxicity and mouse acute toxicity experiments. As a result, Ori effectively dismantles tumorspheres, inhibits proliferation, and reduces the expression of CSC-specific markers. It induces significant differentiation, especially in the case of NB4. Additionally, Ori upregulates TP53 expression, mitigates the hypoxic tumor microenvironment, suppresses stemness, and inhibits PD-L1 expression, prompting a robust anti-cancer immune response. Ori demonstrates pronounced cytotoxicity, inducing notable pro-apoptotic effects on B16F10 and MCF-7 cells, with specific triggering of mitochondrial apoptosis. Importantly, Ori maintains a commendable biosafety record. The dual-action prowess of Ori not only induces the differentiation of CSCs but also dispatches differentiated and residual tumor cells, effectively thwarting the relentless march of tumor progression.

The relationship between appearance anxiety and depression among students in a medical university in China: a serial multiple mediation model.

Background: Appearance anxiety and depression have become common and global public health problems worldwide, especially among adolescents. However, few studies have revealed the mechanisms between them. This study aimed to explore the multiple mediating roles of interpersonal sensitivity and social support between appearance anxiety and depression among medical college students. Methods: With 13 invalid samples excluded, 724 college students participated in our survey and completed questionnaires. The average age of 724 samples was 19.8 ± 2.02 including freshman to senior year and graduate school and above; 31.9% of the participants were male and 68.1% were female. SPSS 25.0 and Hayes' PROCESS macro were used for statistical description, correlation analysis and built multiple mediation models. Results: Appearance anxiety can not only directly affect depression, but also indirectly affect depression through three significant mediating pathways: (1) IS (B = 0.106, 95% CI [0.082-0.132]), which accounted for 49.77% of the total effect, (2) SS (B = 0.018, 95% CI [0.008-0.031]), which accounted for 8.45% of the total effect, and (3) IS and SS (B = 0.008, 95% CI [0.003-0.014]), which accounted for 3.76% of the total effect. And the total mediating effect was 61.97%. Limitations: It is a cross-sectional research method and the causal relationship is unclear. Conclusions: This study found that lower interpersonal sensitivity and higher social support can effectively reduce depression caused by appearance anxiety among college students. The schools and relevant departments should take measures to reduce the interpersonal sensitivity of college students and establish reliable social support, so as to reduce the occurrence of depression.

Asparagine reduces the risk of schizophrenia: a bidirectional two-sample mendelian randomization study of aspartate, asparagine and schizophrenia.

BACKGROUND: Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia. METHODS: This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables. RESULTS: No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483-3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987-1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999-1.011, P-value = 0.132). CONCLUSION: This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.

Patient mistreatment, social sharing of negative events and emotional exhaustion among Chinese nurses: the combined moderating effect of organizational support and trait resilience.

BACKGROUND: As a primary form of work-related violence in the healthcare sector, patient mistreatment negatively impacts nurses' well-being. To date, there has yet reached a definitive conclusion on the mediating mechanism and boundary conditions behind the influence of patient mistreatment on nurses' emotional exhaustion. METHODS: This study employed a convenience sampling method to recruit a sample of 1672 nurses from public hospitals in Western China. The data were collected through anonymous self-report questionnaires and analyzed using hierarchical regression and conditional processes to investigate a theoretical framework encompassing patient mistreatment, emotional exhaustion, social sharing of negative events, organizational support, and trait resilience. RESULTS: Patient mistreatment led to emotional exhaustion among nurses (ß = 0.625, p <.001), and social sharing of negative events mediated this positive relationship (effect = 0.073, SE = 0.013). The combined effects of organizational support and resilience moderated the mediating effect of the social sharing of negative events between patient mistreatment and emotional exhaustion (ß=-0.051, p <.05). Specifically, nurses with a high level of resilience would benefit from organizational support to alleviate emotional exhaustion caused by patient mistreatment. CONCLUSIONS: This study validated a significant positive association between patient mistreatment and emotional exhaustion, which aligns with previous research findings. Integrating conservation of resources theory and goal progress theory, we addressed previous contradictory findings on the impact of social sharing of negative events on emotional exhaustion. Social sharing of negative events served as a mediator between patient mistreatment and emotional exhaustion. Additionally, the moderating effect of organizational support on the relationship between social sharing of negative events and emotional exhaustion depended on individual trait of resilience.