Deep learning permits imaging of multiple structures with the same fluorophores.

Fluorescence microscopy, which employs fluorescent tags to label and observe cellular structures and their dynamics, is a powerful tool for life sciences. However, due to the spectral overlap between different dyes, a limited number of structures can be separately labeled and imaged for live-cell applications. In addition, the conventional sequential channel imaging procedure is quite time consuming, as it needs to switch either different lasers or filters. Here, we propose a novel double-structure network (DBSN) that consists of multiple connected models, which can extract six distinct subcellular structures from three raw images with only two separate fluorescent labels. DBSN combines the intensity-balance model to compensate for uneven fluorescent labels for different structures and the structure-separation model to extract multiple different structures with the same fluorescent labels. Therefore, DBSN breaks the bottleneck of the existing technologies and holds immense potential applications in the field of cell biology.

The association between child maltreatment, cognitive reappraisal, negative coping styles, and non-suicidal self-injury in adolescents with major depressive disorder.

BACKGROUND: Non-suicidal self-injury (NSSI) is a significant public health concern among adolescents with major depressive disorders (MDD). Although previous research has linked child maltreatment (CM) to NSSI, the precise mechanisms remain unclear. This study aims to investigate the association between CM, cognitive reappraisal (CR), negative coping styles (NC) and NSSI in adolescents with MDD, from the perspectives of both Latent Variable Theory and the Network Theory of Mental Disorder. METHODS: A sample of 651 adolescents with MDD was recruited from January to December 2023. Data on CM, CR, NC, and NSSI were collected through paper-based self-reported questionnaires. Data analysis primarily involved structural equation modeling and network analysis. RESULTS: The reporting rate of NSSI among adolescents with MDD was 48.2%. CM showed a significant positive correlation with NSSI. NSSI was affected by CM through three paths: the mediating role of CR, the mediating role of NC, and the chain mediating role of both CR and NC. Emotional abuse (EA) was the central node, while NSSI, EA, and "The urge to cry quietly when faced with troubles"(NC10) were the key bridge nodes. CONCLUSIONS: This study is the first to use both structural equation modeling and network analysis to explore the explore the relationship between CM, CR, NC, and NSSI in adolescents with MDD, providing a theoretical basis for future early prevention and targeted interventions for adolescents with MDD.

Risk Prediction Model for Non-Suicidal Self-Injury in Chinese Adolescents with Major Depressive Disorder Based on Machine Learning.

Background: Non-suicidal self-injury (NSSI) is a significant social issue, especially among adolescents with major depressive disorder (MDD). This study aimed to construct a risk prediction model using machine learning (ML) algorithms, such as XGBoost and random forest, to identify interventions for healthcare professionals working with adolescents with MDD. Methods: This study investigated 488 adolescents with MDD. Adolescents was randomly divided into 75% training set and 25% test set to testify the predictive value of risk prediction model. The prediction model was constructed using XGBoost and random forest algorithms. We evaluated the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, recall, F Score of the two models for comparing the performance of the two models. Results: There were 161 (33.00%) participants having NSSI. Compared without NSSI, there were statistically significant differences in gender (P=0.035), age (P=0.036), depressive symptoms (P=0.042), sleep quality (P=0.030), dysfunctional attitudes (P=0.048), childhood trauma (P=0.046), interpersonal problems (P=0.047), psychoticism (P) (P=0.049), neuroticism (N) (P=0.044), punishing and Severe (F2) (P=0.045) and Overly-intervening and Protecting (M2) (P=0.047) with NSSI. The AUC values for random forest and XGBoost were 0.780 and 0.807, respectively. The top five most important risk predictors identified by both machine learning methods were dysfunctional attitude, childhood trauma, depressive symptoms, F2 and M2. Conclusion: The study demonstrates the suitability of prediction models for predicting NSSI behavior in Chinese adolescents with MDD based on ML. This model improves the assessment of NSSI in adolescents with MDD by health care professionals working. This provides a foundation for focused prevention and interventions by health care professionals working with these adolescents.

Anticancer effects of Erzhimaoling decoction in high-grade serous ovarian cancer in vitro and in vivo.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is a common gynecologic malignancy with a poor prognosis. The traditional Chinese medicine formula Erzhimaoling decoction (EZMLD) has anticancer potential. This study aims to elucidate the anticancer effects of EZMLD on HGSOC in vitro and in vivo. MATERIALS AND METHODS: EZMLD-containing serum was prepared from Sprague-Dawley rats for treating SKOV3 ovarian cancer cells at varying concentrations for 24 h and 48 h to determine the IC50. Concentrations of 0%, 5%, and 10% for 24 h were chosen for subsequent in vitro experiments. The roles of METTL3 and METTL14 in SKOV3 cells were explored by overexpressing these genes and combining EZMLD with METTL3/14 knockdown. Investigations focused on cell viability and apoptosis, apoptosis-related protein expression, and KRT8 mRNA m6A modification. For in vivo studies, 36 BALB/c nude mice were divided into six groups involving EZMLD (6.75, 13.5, and 27 g/kg) and METTL3 or METTL14 knockdowns, with daily EZMLD gavage for two weeks. RESULTS: In vitro, EZMLD-containing serum had IC50 values of 8.29% at 24 h and 5.95% at 48 h in SKOV3 cells. EZMLD-containing serum decreased SKOV3 cell viability and increased apoptosis. EZMLD upregulated METTL3/14 and FAS-mediated apoptosis proteins, while downregulating Keratin 8 (KRT8). EZMLD increased KRT8 mRNA m6A methylation. METTL3/14 overexpression reduced SKOV3 cell viability and increased apoptosis, while METTL3/14 knockdown mitigated EZMLD's effects. In vivo, EZMLD suppressed SKOV3 xenografts growth, causing significant apoptosis and modulating protein expression. CONCLUSIONS: EZMLD has therapeutic potential for ovarian cancer and may be considered for other cancer types. Future research may explore its broader effects beyond cell apoptosis.

Correlation of serum thyrotropin and thyroid hormone levels with diabetic kidney disease: a cross-sectional study.

OBJECTIVE: The relationship between thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and diabetic kidney disease (DKD) is still controversial, and this study analyzed the correlation between TSH, FT3, FT4 and DKD in patients with type 2 diabetes mellitus (T2DM). METHODS: T2DM patients (1216) were divided into five groups based on serum TSH, FT3, and FT4 levels, differences in urinary albumin excretion rate (UACR), estimated glomerular filtration rate (eGFR) were compared. Binary logistic regression verified independent correlations among TSH, FT3, FT4 and UACR, eGFR. TSH and FT3 predictive values for DKD were analyzed using receiver operating characteristic (ROC) curves. RESULTS: The prevalence of albuminuria with decreased eGFR was higher in T2DM patients with subclinical hypothyroidism and overt hypothyroidism than that in patients with normal thyroid function. TSH positively correlated with UACR (r = 0.133, p < 0.001) and positively correlated with eGFR (r = -0.218, p < 0.001), FT3 negatively correlated with UACR (r = -0.260, p < 0.001) and positively correlated with eGFR (r = 0.324, p < 0.001). With the change from the lower normal level to the increased level of TSH and the change from the higher normal level to the reduced level of FT3, the prevalence of albuminuria gradually increased, the prevalence of decreased eGFR gradually increased in TSH groups and FT3 groups. After adjusting for age, BMI, duration of diabetes, TPOAb, TGAb, smoking, drinking, hypertension, the use of anti-diabetic medications (metformin, sodium-glucose cotransporter 2 inhibitors), HbA1c, CRP, TC, TG, LDL-C, and HDL-C, both TSH and FT3 correlated with increased UACR (TSH: OR 1.253, p = 0.001; FT3: OR 0.166, p < 0.001) and decreased eGFR (TSH: OR 1.245, p < 0.001, FT3: OR 0.579, p < 0.001), but this correlation of TSH with eGFR < 60 mL/min/1.73 m2 was not found in male. The area under the ROC curve (AUC) for FT3 was greater than that for TSH (FT3: 0.64; TSH: 0.61). CONCLUSIONS: Increased TSH and reduced FT3 levels were associated with DKD in T2DM patients, but in a sex-dependent manner. FT3 had a higher predictive value for DKD.

Optogenetic Strategies for Optimizing the Performance of Phospholipids Biosensors.

High-performance biosensors play a crucial role in elucidating the intricate spatiotemporal regulatory roles and dynamics of membrane phospholipids. However, enhancing the sensitivity and imaging performance remains a significant challenge. Here, optogenetic-based strategies are presented to optimize phospholipid biosensors. These strategies involves presequestering unbound biosensors in the cell nucleus and regulating their cytosolic levels with blue light to minimize background signal interference in phospholipid detection, particularly under conditions of high expression levels of biosensor. Furthermore, optically controlled phase separation and the SunTag system are employed to generate punctate probes for substrate detection, thereby amplifying biosensor signals and enhancing visualization of the detection process. These improved phospholipid biosensors hold great potential for enhancing the understanding of the spatiotemporal dynamics and regulatory roles of membrane lipids in live cells and the methodological insights in this study might be valuable for developing other high-performance biosensors.

A novel AVPR2 gene mutation in a Chinese pedigree with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.

CRISPR-repressed toxin-antitoxin provides herd immunity against anti-CRISPR elements.

Prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are highly vulnerable to phage-encoded anti-CRISPR (Acr) factors. How CRISPR-Cas systems protect themselves remains unclear. Here we uncovered a broad-spectrum anti-anti-CRISPR strategy involving a phage-derived toxic protein. Transcription of this toxin is normally repressed by the CRISPR-Cas effector but is activated to halt cell division when the effector is inhibited by any anti-CRISPR proteins or RNAs. We showed that this abortive infection-like effect efficiently expels Acr elements from bacterial population. Furthermore, we exploited this anti-anti-CRISPR mechanism to develop a screening method for specific Acr candidates for a CRISPR-Cas system and successfully identified two distinct Acr proteins that enhance the binding of CRISPR effector to nontarget DNA. Our data highlight the broad-spectrum role of CRISPR-repressed toxins in counteracting various types of Acr factors. We propose that the regulatory function of CRISPR-Cas confers host cells herd immunity against Acr-encoding genetic invaders whether they are CRISPR targeted or not.

Association of geriatric nutritional risk index with bone mineral density and osteoporosis in postmenopausal elderly women with T2DM.

BACKGROUND AND OBJECTIVES: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). METHODS AND STUDY DESIGN: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. RESULTS: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the nor-mal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). CONCLUSIONS: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.

LexA, an SOS response repressor, activates TGase synthesis in Streptomyces mobaraensis.

Transglutaminase (EC 2.3.2.13, TGase), an enzyme that catalyzes the formation of covalent cross-links between protein or peptide molecules, plays a critical role in commercial food processing, medicine, and textiles. TGase from Streptomyces is the sole commercial enzyme preparation for cross-linking proteins. In this study, we revealed that the SOS response repressor protein LexA in Streptomyces mobaraensis not only triggers morphological development but also enhances TGase synthesis. The absence of lexA significantly diminished TGase production and sporulation. Although LexA does not bind directly to the promoter region of the TGase gene, it indirectly stimulates transcription of the tga gene, which encodes TGase. Furthermore, LexA directly enhances the expression of genes associated with protein synthesis and transcription factors, thus favorably influencing TGase synthesis at both the transcriptional and posttranscriptional levels. Moreover, LexA activates four crucial genes involved in morphological differentiation, promoting spore maturation. Overall, our findings suggest that LexA plays a dual role as a master regulator of the SOS response and a significant contributor to TGase regulation and certain aspects of secondary metabolism, offering insights into the cellular functions of LexA and facilitating the strategic engineering of TGase overproducers.

Synchronous profiling of mRNA N6-methyladenosine modifications and mRNA expression in high-grade serous ovarian cancer: a pilot study.

This study aimed to synchronously determine epitranscriptome-wide RNA N6-methyladenosine (m6A) modifications and mRNA expression profile in high grade serous ovarian cancer (HGSOC). The methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to comprehensively examine the m6A modification profile and the RNA-sequencing (RNA-seq) was performed to analyze the mRNA expression profile in HGSOC and normal fallopian tube (FT) tissues. Go and KEGG analyses were carried out in the enrichment of those differentially methylated and expressed genes. MeRIP-seq data showed 53,794 m6A methylated peaks related to 19,938 genes in the HGSOC group and 51,818 m6A peaks representing 19,681 genes in the FT group. RNA-seq results revealed 2321 upregulated and 2486 downregulated genes in HGSOC. Conjoint analysis of MeRIP-seq and RNA-seq data identified differentially expressed genes in which 659 were hypermethylated (330 up- and 329 down-regulated) and 897 were hypomethylated (475 up- and 422 down-regulated). Functional enrichment analysis indicated that these differentially modulated genes are involved in pathways related to cancer development. Among methylation regulators, the m6A eraser (FTO) expression was significantly lower, but the m6A readers (IGF2BP2 and IGF2BP3) were higher in HGSOC, which was validated by the subsequent real-time PCR assay. Exploration through public databases further corroborated their possible clinical application of certain methylation regulators and differentially expressed genes. For the first time, our study screens the epitranscriptome-wide m6A modification and expression profiles of their modulated genes and signaling pathways in HGSOC. Our findings provide an alternative direction in exploring the molecular mechanisms of ovarian pathogenesis and potential biomarkers in the diagnosis and predicting the prognosis of the disease.

SIRT3: A Potential Target of Different Types of Osteoporosis.

Osteoporosis (OP) is a common age-related disease. OP is mainly a decrease in bone density and mass caused by the destruction of bone microstructure, which leads to an increase in bone fragility. SIRT3 is a mitochondrial deacetylase that plays critical roles in mitochondrial homeostasis, metabolic regulation, gene transcription, stress response, and gene stability. Studies have shown that the higher expression levels of SIRT3 are associated with decreased levels of oxidative stress in the body and may play important roles in the prevention of age-related diseases. SIRTs can enhance the osteogenic potential and osteoblastic activity of bone marrow mesenchymal stromal cells not only by enhancing PGC-1α, FOXO3, SOD2, and oxidative phosphorylation, but also by anti-aging and reducing mitochondrial autophagy. SIRT3 is able to upregulate antioxidant enzymes to exert an inhibitory effect on osteoclasts, however, it has been shown that the inflammatory cascade response can in turn increase SIRT3 and inhibit osteoclast differentiation through the AMPK-PGC-1ß pathway. SIRT3 plays an important role in different types of osteoporosis by affecting osteoblasts, osteoclasts, and bone marrow mesenchymal cells. In this review, we discuss the classification and physiological functions of SIRTs, the effects of SIRT3 on OCs osteoblasts, and BMSCs, and the roles and mechanisms of SIRT3 in different types of OP, such as diabetic OP, glucocorticoid-induced OP, postmenopausal OP, and senile OP.

Association between serum ferritin and bone turnover marker levels in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease.

OBJECTIVE: To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), ß-I type collagen carboxy-terminal peptide (ß-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed. RESULTS: Compared with the T2DM+non-HF group, ß-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, ß-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with ß-CTx [ß = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [ß=-0.108; 95%CI (-0.006, -0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between ß-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith ß-CTx [ß = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [ß=-0.124; 95% CI (0.007,0.001) and ß=-0.168; 95% CI (-0.012, -0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [ß=-0.117; 95% CI (-0.007, -0.001) and ß=-0.003; 95% CI (-0.013, -0.003)]. CONCLUSION: SF level was positively correlated with ß-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.

The relationship between advanced liver fibrosis and osteoporosis in type 2 diabetes patients with MAFLD.

PURPOSE: To investigate the relationship between advanced liver fibrosis and osteoporosis in metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 1144 T2DM patients were divided into the MAFLD and non-MAFLD groups, 460 T2DM patients with MAFLD (277 males aged ≥50 years and 183 postmenopausal females) were divided into N1 (advanced liver fibrosis excluded), N2 (indeterminate advanced liver fibrosis), and N3 (advanced liver fibrosis) groups according to the non-alcoholic fatty liver fibrosis score (NFS), the differences in bone mineral density (BMD) levels and prevalence of osteoporosis were compared. Based on the tertile levels of BMD of the lumbar spine (L), T2DM patients were divided into three groups (T1, T2, and T3), and the differences in the prevalence of advanced liver fibrosis were compared. RESULTS: The BMD levels of the L4, and L1-4 in the MAFLD group were lower than those of the non-MAFLD groups in male and female T2DM patients .The BMD levels of the total hip, L4, and L1-4 in the N3 group were lower than those of the N2 and N1 groups in male and female T2DM patients with MAFLD, and the prevalence of osteoporosis in the N3 group of males was higher than that in the N1 group. The BMD levels of the total hip, L4, and L1-4 were negatively correlated with NFS in both males and females. The BMD levels of the total hip and L4 in males, and the BMD level of L4 in females were negatively associated with NFS. The prevalence of advanced liver fibrosis was higher in the T1 group than in the T2 and T3 groups in T2DM patients with MAFLD. CONCLUSION: The BMD levels in male aged ≥50 years or postmenopausal female diabetic patients with MAFLD were negatively correlated with the degree of advanced liver fibrosis, which means an increased risk of liver fibrosis with decreasing BMD.

Exploring the Effects of Online Physician Voice Pitch Range and Filled Pauses on Patient Satisfaction in Mobile Health Communication.

The convenience of mobile devices has driven the widespread use of voice technology in mobile health communication, significantly improving the timeliness of online service. However, the issue of listening to therapeutic content, which requires great cognitive effort and may exceed the patient's information processing capacity (i.e., information overload), is of concern. Based on information processing theory, this study reports how online physicians' voice characteristics (pitch range and filled pauses) affect patient satisfaction. We obtained 10,585 mobile voice consultation records of 1,416 doctors from China's largest mHealth platform and analyzed them using audio mining and empirical methods. Results showed that pitch range (ß = 0.0539, p < .01) and filled pauses (ß = 0.0365, p < .01) in doctors' voice positively influenced online patient satisfaction. However, the effect of filled pauses becomes weaker for patients with higher health literacy and higher disease risk. This suggests that there is heterogeneity in the way different patients process audio information. This study provides important insights for guiding online physician behaviors, enhancing patient satisfaction, and improving mobile health platform management.

The Effect of Tirzepatide on Weight, Lipid Metabolism and Blood Pressure in Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Aim: To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM). Methods: Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM. Results: Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss >5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=-2.07, 95% CI (-2.52, -1.63) and MD=-3.14, 95% CI (-4.42, -1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c<7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.

Adverse event profile of CGRP monoclonal antibodies: findings from the FDA adverse event reporting database.

BACKGROUND: Four CGRP Monoclonal Antibodies (mAbs) have been approved for migraine prophylaxis by the Food and Drug Administration (FDA) since 2018. However, there are concerns about the safety of these four drugs for real-world use. OBJECTIVE: To compare the adverse event profiles of four CGRP-mAbs with FAERS data. METHODS: The study was based on records from the FAERS database. Only reports containing one of the active ingredients with CGRP-mAbs were included in this study. Disproportionality analyses including but not limited to reporting odds ratio (ROR) and information components (IC) were conducted to identify drug-AE associations. RESULTS: In total, 58110 reports were identified for CGRP-mAbs. 80 overlapping signals were disproportionately reported. They affected a range of organs and systems, including the gastrointestinal and cardiovascular systems, skin, and hair. Additionally, the rare cardiovascular adverse events were significantly different among the four CGRP-mAbs. CONCLUSION: We identified numerous shared underlying signals (overlapping signals) for CGRP-mAbs as suspected drugs in multiple systems and organs. The unlabeled common signals may indicate potential safety issues. In addition, the underlying safety signals varied among the four CGRP-mAbs, particularly in the cardiovascular system, and further studies are needed to confirm these associations and the potential clinical implications.

The relationship between childhood maltreatment and non-suicidal self-injury in adolescents with depressive disorders.

This study aims to explore the core symptoms of Non-Suicidal Self-Injury (NSSI) in adolescents with depressive disorders and the relationship between childhood maltreatment (CM) and NSSI symptoms by using network analysis. A total of 689 adolescents with depressive disorders participated in the survey. The Chinese version of the Adolescent Non-Suicidal Self-Injury Assessment Questionnaire (ANSAQ) and the Short Form of the Childhood Trauma Questionnaire (CTQ-SF) were employed to measure NSSI and the symptoms of CM, respectively. Using network analysis, the NSSI network and the CM-NSSI network were constructed to identify the most central symptoms and the bridge symptoms within the networks. Within the NSSI network, "Intentional scratches", " Intentionally hitting hard objects with your head ", " Intentionally hitting oneself with fists or harder objects ", and " Intentional pinching " were identified as the primary symptoms of NSSI. "emotional abuse", "sexual abuse", and " Intentionally cut yourself " emerged as three key bridge symptoms linking CM with NSSI. This research is the first to investigate the symptom network of CM-NSSI in a sample of adolescents with depressive disorders, providing a foundation for subsequent NSSI prevention and the development of targeted intervention strategies.

Association of spontaneous abortion with bipolar disorder and major depression based on inverse probability treatment weighting of multigroup propensity scores: Evidence from the UK Biobank.

BACKGROUND: Few studies have explored the association between the number of SAs and bipolar disorder and major depression (BDMD). This study aims to investigate the association between SA and BDMD, and the possible dose-response relationship between them. METHODS: We conducted a cross-sectional study of 13,200 female UK Biobank participants. Participants were classified into BDMD and no-BDMD groups based on their BDMD status. The number of SAs was grouped into non-SA, occasional SA (OSA), and recurrent SA (RSA). Baseline characteristics of the three groups were balanced using inverse probability treatment weighting (IPTW) based on propensity scores. The three-knots restricted cubic spline regression model was utilized to assess the dose-response relationship between the number of SAs and BDMD. RESULTS: The IPTW-adjusted multivariate logistic regression revealed that SA was an independent risk factor for BDMD, with adjusted OR of 1.12 (95 % CI: 1.07-1.19) and 1.32 (95 % CI: 1.25-1.40) in the OSA and RSA groups, respectively. The strength of this association amplified as the number of SAs (P for trend <0.001). There was a nonlinear relationship between the number of SAs and the risk of BDMD, with an approximately inverted L-shaped curve. LIMITATIONS: The information of the SA and BDMD status relied on self-reported by volunteers, and the study sample was mostly of European descent. CONCLUSIONS: Women who reported experiencing multiple SAs are more likely to have BDMD. Therefore, it is imperative to provide psychological care and interventions for women in the postpartum period.

Regression equation for predicting dietary phosphorus intake based on estimated dietary protein intake: A multicenter cross-sectional study in China.

BACKGROUND: Protein and phosphorus intake, which affect chronic kidney disease (CKD), is assessed using cumbersome food diaries. Therefore, more straightforward and accurate methods of assessing protein and phosphorus intake are needed. We decided to investigate the nutrition status and dietary protein and phosphorus intake of patients with stages 3, 4, 5, or 5D CKD. METHODS: This cross-sectional survey included outpatients with CKD at seven class A tertiary hospitals in Beijing, Shanghai, Sichuan, Shandong, Liaoning, and Guangdong in China. Protein and phosphorus intake levels were calculated using 3-day food records. Protein levels and calcium and phosphorus serum concentrations were measured; urinary urea nitrogen was determined using a 24-h urine test. Protein and phosphorus intakes were calculated using the Maroni and Boaz formulas, respectively. The calculated values were compared with the recorded dietary intakes. An equation that regressed phosphorus intake on protein intake was constructed. RESULTS: The average recorded energy and protein intake was 1637.5 ± 595.74 kcal/day and 56.97 ± 25.25 g/day, respectively. Overall, 68.8% of patients had a good nutrition status (grade A on the Subjective Global Assessment). The correlation coefficient between protein intake and calculated intake was 0.145 (P = 0.376) and that between phosphorus intake and calculated intake was 0.713 (P < 0.001). CONCLUSION: Protein and phosphorus intakes correlated linearly. Chinese patients with stage 3-5 CKD had low daily energy intake but high protein intake. Malnutrition was present in 31.2% of patients with CKD. The phosphorus intake could be estimated from the protein intake.