Chevron osteotomy and scarf osteotomy for hallux valgus angle and intermetatarsal angle correction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis aimed to investigate the differences in hallux valgus angle (HVA), intermetatarsal angle (IMA), American Orthopedic Foot and Ankle Society (AOFAS) scores, and complication rates between chevron osteotomy and scarf osteotomy for correcting hallux valgus. METHODS: Two investigators independently searched for randomized controlled trials (RCTs) published from 2007 to 2018 on PubMed, Web of Science, and Cochrane Library databases. Next, chevron and scarf osteotomies were compared for their postoperative outcomes using HVA, IMA, and AOFAS scores and their complication rates. Meta-analysis was performed using Review Manager (version 5.3). RESULTS: Six RCTs-comprising 507 feet, of which 261 and 246 underwent chevron and scarf osteotomies, respectively-were included. The meta-analysis revealed that chevron osteotomy led to significantly smaller postoperative HVAs than scarf osteotomy (weighted mean difference [WMD] = -1.94, 95% CI = - 2.65 to - 1.29, P < .00001). However, the differences in postoperative IMA (WMD = - 0.44, 95% CI = - 1.10 to 0.22, P = .19), postoperative AOFAS scores (WMD = 0.75; 95% CI = - 5.32 to 6.82; P = .81), and complication rates (risk ratio = 1.22, 95% CI = 0.65-2.27, P = .53) between feet that underwent chevron and scarf osteotomies were nonsignificant. CONCLUSIONS: Compared with scarf osteotomy, chevron osteotomy had significantly more favorable postoperative outcomes in terms of HVA correction, but not in terms of IMA, AOFAS scores, or complication rates. LEVEL OF EVIDENCE: Level I, systemic review and meta-analysis.

Adipocyte-secreted PRELP promotes adipocyte differentiation and adipose tissue fibrosis by binding with p75NTR to activate FAK/MAPK signaling.

Adipocyte-secreted factors intricately regulate adipose tissue function, and the underlying molecular mechanisms are only partially understood. However, the function of PRELP, which is a key component of the extracellular matrix (ECM) in adipocytes, remains largely unknown. In this study, we demonstrate that PRELP was upregulated in both obese humans and mice, which exhibited a positive correlation with metabolic disorders. PRELP knockout could resist HFD-induced obesity and inhibit adipocyte differentiation. PRELP knockout improved glucose tolerance, insulin sensitivity and alleviated adipose tissue fibrosis. Mechanistically, PRELP was secreted into the ECM and bound to the extracellular domain of its receptor p75NTR in adipocytes, which further activated the FAK/MAPK (JNK, p38 MAPK, ERK1/2) signaling pathway, promoting adipocyte differentiation and exacerbating adipocyte fibrosis. Adipocyte PRELP plays a pivotal role in regulating obesity and adipose tissue fibrosis through an autocrine manner, and PRELP may be a therapeutic target for obesity and its related metabolic disorders.

Artificial intelligence interpretation of touch print smear cytology of testicular specimen from patients with azoospermia.

PURPOSE: Identification of mature sperm at microdissection testicular sperm extraction (mTESE) is a crucial step of sperm retrieval to help patients with non-obstructive azoospermia (NOA) proceed to intracytoplasmic sperm injection. Touch print smear (TPS) cytology allows immediate interpretation and prompt sperm identification intraoperatively. In this study, we leverage machine learning (ML) to facilitate TPS reading and conquer the learning curve for new operators. MATERIALS AND METHODS: One hundred seventy-six microscopic TPS images from the testicular specimen of patients with azoospermia at Taipei Veterans General Hospital were retrospectively collected, including categories of Sertoli cell, primary spermatocytes, round spermatids, elongated spermatids, immature sperm, and mature sperm. Among them, 118 images were assigned as the training set and 29 images as the validation set. RetinaNet (Lin et al. in IEEE Trans Pattern Anal Mach Intell. 42:318-327, 2020), a one-stage detection framework, was adopted for cell detection. The performance was evaluated at the cell level with average precision (AP) and recall, and the precision-recall (PR) curve was displayed among an independent testing set that contains 29 images that aim to assess the model. RESULTS: The training set consisted of 4772 annotated cells, including 1782 Sertoli cells, 314 primary spermatocytes, 443 round spermatids, 279 elongated spermatids, 504 immature sperm, and 1450 mature sperm. This study demonstrated the performance of each category and the overall AP and recall on the validation set, which were 80.47% and 96.69%. The overall AP and recall were 79.48% and 93.63% on the testing set, while increased to 85.29% and 93.80% once the post-meiotic cells were merged into one category. CONCLUSIONS: This study proposed an innovative approach that leveraged ML methods to facilitate the diagnosis of spermatogenesis at mTESE for patients with NOA. With the assistance of ML techniques, surgeons could determine the stages of spermatogenesis and provide timely histopathological diagnosis for infertile males.

EAT-Lancet Diet Pattern, Genetic Predisposition, Inflammatory Biomarkers, and Risk of Lung Cancer Incidence and Mortality.

SCOPE: The association between a planetary and sustainable EAT-Lancet diet and lung cancer remains inconclusive, with limited exploration of the role of genetic susceptibility and inflammation. METHODS AND RESULTS: The study includes 175 214 cancer-free participants in the UK Biobank. Fourteen food components are collected from a 24-h dietary recall questionnaire. A polygenic risk score is constructed through capturing the overall risk variants for lung cancer. Sixteen inflammatory biomarkers are assayed in blood samples. Participants with the highest EAT-Lancet diet scores (≥12) have a lower risk of lung cancer incidence (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.51-0.80) and mortality (HR = 0.65, 95% CI: 0.48-0.88), compared to those with the lowest EAT-Lancet diet scores (≤8). Interestingly, there is a significantly protective trend against both lung adenocarcinoma and lung squamous cell carcinoma with higher EAT-Lancet diet scores. Despite no significant interactions, a risk reduction trend for lung cancer is observed with increasing EAT-Lancet diet scores and decreasing genetic risk. Ten inflammatory biomarkers partially mediate the association between the EAT-Lancet diet and lung cancer risk. CONCLUSION: The study depicts a lower risk of lung cancer conferred by the EAT-Lancet diet associated with lower inflammation levels among individuals with diverse genetic predispositions.

LUTS/BPH increases the risk of depressive symptoms among elderly adults: A 5-year longitudinal evidence from CHARLS.

OBJECTIVE: The prevalence of Lower Urinary Tract Symptoms suggestive of Benign Prostatic Hyperplasia (LUTS/BPH) is notably high and potentially elevates the likelihood of depressive symptoms. This study was designed to employ both cross-sectional and longitudinal methodologies to explore the correlation between LUTS/BPH and depressive symptoms among middle-aged and elderly men in China. METHODS: This investigation utilized data from the China Health and Retirement Longitudinal Study (CHARLS), with the initial dataset from 2015 serving as the baseline and subsequent data from 2018 and 2020 facilitating longitudinal analysis. The study encompassed a baseline cohort of 5156 men aged 45 years and above, and an expansive longitudinal analytical sample of 23,530 participants spanning from 2015 to 2020. The assessment of depressive symptoms was conducted using the 10-item Center for Epidemiological Studies Depressive Symptoms Scale (CESD-10). To investigate the factors associated with LUTS/BPH, the relationship between LUTS/BPH and depressive symptoms, and to evaluate the incidence rate of depressive symptoms onset based on LUTS/BPH status, multivariate logistic analyses and logistic regression models were employed. RESULTS: Our results reveal a markedly higher incidence of depressive symptoms among individuals with LUTS/BPH, at 30.16 %, compared to 22.94 % in those without LUTS/BPH. This pattern was consistent in both mild and moderate depressive symptoms categories. However, the prevalence of severe depressive symptoms did not exhibit a significant disparity between the two groups. Longitudinal analysis spanning from 2015 through 2018 and 2020 further corroborated these observations. Individuals with LUTS/BPH showed a substantially higher incidence of depressive symptoms across all severity levels compared to those without LUTS/BPH. Specifically, the presence of LUTS/BPH was linked to a 53 % heightened risk of mild depressive symptoms, a 45 % increase in moderate depressive symptoms, and an alarming 229 % surge in severe depressive symptoms risk between 2015 and 2018. Additionally, from 2015 to 2020, there was a 30 % increased risk for mild depressive symptoms, a 41 % rise for moderate depressive symptoms, and a 106 % escalation in the risk of severe depressive symptoms among those with LUTS/BPH. CONCLUSION: In middle-aged and older Chinese adults, LUTS/BPH were correlated with an elevated risk of depressive symptoms.

Sex disparity in the association between metabolic-anthropometric phenotypes and risk of obesity-related cancer: a prospective cohort study.

BACKGROUND: Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex. METHODS: A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models. RESULTS: We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape. CONCLUSIONS: There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account.

Time of day-dependent alterations of ferroptosis in LPS-induced myocardial injury via Bmal-1/AKT/ Nrf2 in rat and H9c2 cell.

Background: One of the most prevalent causes of death in sepsis is sepsis-induced cardiomyopathy (SICM). Circadian disruption is involved in the progress of sepsis. However, the molecular mechanism remains unclear. Methods: Here, we built LPS-induced SICM in-vivo and in-vitro models. LPS was administrated at the particular Zeitgeber times (ZT), ZT4-ZT10-ZT16-ZT22 and ZT10-ZT22 in vivo and vitro experiments, respectively. Results: In vivo experiment, injection of LPS at ZT10 induced higher infiltration of inflammatory cells and content of intracellular Fe2+, and lower level of Glutathione peroxidase 4 (GPX4) and cardiac function than other ZTs (P < 0.05), which indicated that myocardial ferroptosis in septic rat presented a time of day-dependent manner. Bmal-1 protein and mRNA levels of injection of LPS at ZT10 were lower than those at other three ZTs (P < 0.05). The ratios of pAKT/AKT at ZT4 and ZT10 LPS injection were lower than those at ZT16 and ZT22 (P < 0.05). Nrf2 protein levels at ZT10 LPS injection were lower than those at other three ZTs (P < 0.05). These results indicated that the circadian of Bmal-1 and its downstream AKT/Nrf2 pathway in rat heart were inhibited under SICM condition. Consistent with in-vivo experiment, we found LPS could significantly reduce the expressions of Bmal-1 protein and mRNA in H9c2 cell. Up-regulation of Bmal-1 could reduce the cell death, oxidative stress, ferroptosis and activation of AKT/Nrf2 pathway at both ZT10 and ZT22 LPS administration. Conversely, its down-regulation presented opposite effects. AKT siRNA could weaken the effect of Bmal-1 pcDNA. Conclusion: Ferroptosis presented the time of day-dependent manners via Bmal-1/AKT/Nrf2 in vivo and vitro models of SICM.

Huangqi-Danshen Decoction Against Renal Fibrosis in UUO Mice via TGF-ß1 Induced Downstream Signaling Pathway.

Background: Huangqi-Danshen decoction (HDD) is a Chinese medicinal herb pair with good efficacy in treating chronic kidney disease, but its mechanism needs to be clarified. Aim: To uncover the underlying mechanism of HDD antagonizing renal fibrosis through network pharmacology (NP) analysis and experimental validation. Materials and Methods: The chemical components of water extract of HDD were analyzed by combining the ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrum analysis (UHPLC-QE-MS) and HERB database. NP was used to identify core common targets of HDD components and renal fibrosis. Subsequently, male C57BL/6 mice were divided into Sham, unilateral ureteral obstruction (UUO) and UUO+HDD groups. Renal function, histopathology, Western blotting, and immunohistochemistry analyses were used to evaluate the protective effect of HDD on UUO mice. The effects of HDD on signaling pathways were validated in both UUO mice and transforming growth factor-ß1 (TGF-ß1)-induced HK-2 cells. Results: By combining UHPLC-QE-MS analysis and HERB database, 25 components were screened in HDD extract. There were 270 intersection targets of the 25 components and renal fibrosis. Based on their scores in protein-protein interaction analysis and degree values in component-pathway-target triadic network, 6 core common targets of the 25 components and renal fibrosis were identified, namely phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription 3 (Stat3), non-receptor tyrosine kinase Src (Src), epidermal growth factor receptor (EGFR), matrix metalloproteinase 9 (MMP9), and MMP2. HDD ameliorated renal tubular damage and collagen deposition and downregulated fibrosis-related proteins expression in UUO mice. Furthermore, HDD was demonstrated to reduce PI3K, Stat3, Src, EGFR, and MMP2 expressions, and enhance MMP9 expression in the kidney of UUO mice and in TGF-ß1-induced HK-2 cells. Conclusion: HDD can alleviate renal fibrosis which may be related to regulating the expression of essential proteins in the epithelial-mesenchymal transition and extracellular matrix production/degradation signaling pathways.

Discordant Wada and fMRI language lateralization: a case report.

Functional MRI (fMRI) is gaining importance in the preoperative assessment of language for presurgical planning. However, inconsistencies with the Wada test might arise. This current case report describes a very rare case of an epileptic patient who exhibited bilateral distribution (right > left) in the inferior frontal gyrus (laterality index [LI] = -0.433) and completely right dominance in the superior temporal gyrus (LI = -1). However, the Wada test revealed a dissociation: his motor speech was located in the left hemisphere, while he could understand vocal instructions with his right hemisphere. A clinical implication is that the LIs obtained by fMRI should be cautiously used to determine Broca's area in atypical patients; for example, even when complete right dominance is found in the temporal cortex in right-handed patients. Theoretically, as the spatially separated functions of motor speech and language comprehension (by the combined results of fMRI and Wada) can be further temporally separated (by the intracarotid amobarbital procedure) in this case report, these findings might provide direct support to Broca's initial conclusions that Broca's area is associated with acquired motor speech impairment, but not language comprehension per se. Moreover, this current finding supports the idea that once produced, motor speech can be independent from language comprehension.

Response of sulfate concentration to eutrophication on spatio-temporal scale in freshwater lakes.

The dramatical increase of sulfur concentration in eutrophic lakes, especially sulfate (SO42-), has brought attention to the impact on the lake ecosystem; however, the mechanisms driving the intensification of eutrophication and the role of SO42- concentrations remain poorly understood. To assess the impact of eutrophication on SO42- dynamics in lakes, this study monitored SO42- concentrations in water and sediments across seven lakes with varying trophic statuses on a spatial scale, and in the eutrophic Lake Taihu over one year on a temporal scale, as well as a series of microcosms with different initial SO42- concentrations. Exogenous sulfur input is the primary driver of increased SO42- concentrations in lakes, the highest SO42- concentration in overlying water was 100 mg/L, as well as which reached 310.9 mg/L in sediment. The concurrent input of nutrients such as nitrogen and phosphorus exacerbated eutrophication, resulting in the destabilization of the sulfur cycle. Eutrophication promoted the SO42- concentration on the spatio-temporal scale, especially in sediment, and trophic lake index (TLI) showed a positive correlation with the SO42- in sediments (R2 = 0.99; 0.88). The SO42- concentration in water and TLI showed a nonlinear correlation on the temporal scale (R2 = 0.44), and showed a positive correlation on the spatial scale (R2 = 0.49). Microscopic experiments demonstrate that the anaerobic environment created by cyanobacteria decomposition induced sulfate reduction and significantly reduces SO42- concentrations. Concurrently, the anaerobic environment facilitates the coupling of iron reduction with sulfate reduction, leading to a substantial increase in Acid Volatile Sulfides (AVS) in the sediment. These findings reveal that eutrophication has a dual effect on the dynamic change of SO42- concentrations in overlying water, which is helpful to accurately evaluate and predict the change of SO42- concentrations in lakes.

Dynamic networks of complex posttraumatic stress disorder and depression among college students with childhood trauma: insights from cross-sectional and cross-lagged panel network analysis.

Background and Objective: There is a current research gap regarding the symptom structure and underlying causal relationships between complex posttraumatic stress disorder (CPTSD) and depressive symptoms. This longitudinal study used a cross-sectional network and cross-lag panel network (CLPN) to examine how CPTSD and depression symptoms interact over time in Chinese college students with childhood trauma.Methods: From 18,933 college students who took part in 2 surveys 12 months apart, 4006 participants (mean age: 20.07 ± 2.04) who reported childhood trauma were screened. Within this sample, there were 2354 (58.8%) males and 1652 (41.2%) females.Results: In the one-year interval CLPN model, it was found that depressive symptoms may precede other symptoms. Specifically, negative emotions and negative self-evaluations are more likely to predict subsequent symptoms. Conversely, in CPTSD, symptoms related to fear and anxiety, such as avoidance, intrusion, and hyperarousal, are more frequently activated by other symptoms, including negative emotionsConclusions: This finding offers a novel perspective on the interplay between CPTSD and depression, extending the existing theory. From a clinical standpoint, the points of intervention for comorbidity between depression and CPTSD who have experienced childhood trauma differ across different stages.

This study used network analysis to examine the evolving symptom structure of complex posttraumatic stress disorder (CPTSD) and depression, as well as the relationships between symptoms, in a large-scale longitudinal study among college students who have experienced childhood trauma.Symptoms such as emotional dysregulation and negative self-concept serve as stable central symptoms of both CPTSD and depression.Depression, tends to activate other symptoms, whereas CPTSD, is more frequently predicted by other symptoms.

Influence of chronotype on sleep quality and menstrual regularity in nurses on monthly shift rotations.

OBJECTIVES: This study was to investigate factors that influence the sleep quality and menstrual cycles of female rotating-shift nurses. METHODS: A cross-sectional study was conducted in which 213 female rotating-shift nurses between the ages of 20 and 45 were recruited from a medical center in Taiwan from November 1, 2023, to December 31, 2023. Binary logistic regression analysis was performed with regard to sleep quality or menstrual cycle. RESULTS: Female rotating-shift nurses who perceived a higher level of stress (p < .001), were late chronotypes (p = .020), or were working the night shift (p = .006) were more likely to have poor sleep quality. Late-type nurses working the day shift were more likely to have poor sleep quality than were early- and intermediate-type nurses (p < .001). With regard to menstrual cycles, female rotating-shift nurses who perceived a higher level of stress (p = .008), were working the night shift (p < .001), or had poor sleep quality (p = .001) were more likely to have irregular menstrual cycles. Late-type nurses working the day shift were more likely to have irregular menstrual cycles than were early- and intermediate-type nurses (p = .013). CONCLUSIONS: A higher likelihood of poor sleep quality was found in female rotating-shift nurses when they perceived high levels of stress, and the interactions between chronotype and shift type could influence sleep quality. Shift type and the interactions between chronotype and shift type could also influence menstrual regularity.

CRISPR/Cas9-mediated exon skipping to restore premature translation termination in a DFNB4 mouse model.

SLC26A4 encodes pendrin, a crucial anion exchanger essential for maintaining hearing function. Mutations in SLC26A4, including the prevalent c.919-2 A > G splice-site mutation among East Asian individuals, can disrupt inner ear electrolyte balance, leading to syndromic and non-syndromic hearing loss, such as Pendred syndrome and DFNB4. To explore potential therapeutic strategies, we utilized CRISPR/Cas9-mediated exon skipping to create a Slc26a4∆E8+E9/∆E8+E9 mouse model. We assessed pendrin expression in the inner ear and evaluated vestibular and auditory functions. The Slc26a4∆E8+E9/∆E8+E9 mice demonstrated reframed pendrin in the inner ear and normal vestibular functions, contrasting with severely abnormal vestibular functions observed in the Slc26a4 c.919-2 A > G splicing mutation mouse model. However, despite these molecular achievements, hearing function did not show the expected improvement, consistent with observed pathology, including cochlear hair cell loss and elevated hearing thresholds. Consequently, our findings highlight the necessity for alternative genetic editing strategies to address hearing loss caused by the SLC26A4 c.919-2 A > G mutation.

Genetic Aspects of Necrobiotic Xanthogranuloma.

This genetic association study examines the genetic aspects of necrobiotic xanthogranuloma in 3 patients in China.

Recent advances and clinical applications of red blood cell lifespan measurement.

The red blood cell (RBC) lifespan is a crucial indicator used in clinical diagnostics, treatment, and disease monitoring. This biomarker quantifies the duration that red blood cells (RBCs) circulate within the bloodstream after being released from the bone marrow, serving as a sensitive and direct indicator of red blood cell turnover. Conventional techniques for RBC lifespan measurement, including differential agglutination, 51Cr labeling, and 15N glycine labeling, each present their own set of challenges, such as complexity, radioactive exposure, and potential allergic reaction. The carbon monoxide (CO) breath test has emerged as an advanced and non-invasive alternative, indirectly assessing RBC lifespan through hemoglobin (Hb) renewal rates. This method is convenient, rapid, and lacks the drawbacks of traditional approaches. The CO breath test for RBC lifespan is widely utilized in benign anemia, malignant hematological disorders, neonatal hyperbilirubinemia, and diabetes mellitus, offering valuable insights into disease mechanisms, progression, and treatment outcomes.

Contrast-enhanced ultrasound image sequences based on radiomics analysis for diagnosis of metastatic cervical lymph nodes from thyroid cancer.

Background: Thyroid cancer (TC) prone to cervical lymph node (CLN) metastasis both before and after surgery. Ultrasonography (US) is the first-line imaging method for evaluating the thyroid gland and CLNs. However, this assessment relies mainly on the subjective judgment of the sonographer and is very much dependent on the sonographer's experience. This prospective study was designed to construct a machine learning model based on contrast-enhanced ultrasound (CEUS) videos of CLNs to predict the risk of CLN metastasis in patients with TC. Methods: Patients who were proposed for surgical treatment due to TC from August 2019 to May 2020 were prospectively included. All patients underwent US of CLNs suspected of metastasis, and a 2-minute imaging video was recorded. After target tracking, feature extraction, and feature selection through the lymph node imaging video, three machine learning models, namely, support vector machine, linear discriminant analysis (LDA), and decision tree (DT), were constructed, and the sensitivity, specificity, and accuracy of each model for diagnosing lymph nodes were calculated by leave-one-out cross-validation (LOOCV). Results: A total of 75 lymph nodes were included in the study, with 42 benign cases and 33 malignant cases. Among the machine learning models constructed, the support vector machine had the best diagnostic efficacy, with a sensitivity of 93.0%, a specificity of 93.8%, and an accuracy of 93.3%. Conclusions: The machine learning model based on US video is helpful for the diagnosis of whether metastasis occurs in the CLNs of TC patients.

Chaihu Guizhi Decoction prevents cognitive, memory impairments and sensorimotor gating deficit induced by N-methyl-d-aspartate receptor antibody in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Anti-NMDAR encephalitis is one of the most common types of autoimmune encephalitis, primarily presenting with prodromal symptoms, such as fever and headache, followed by a range of neurological and psychiatric symptoms. Chaihu Guizhi Decoction (CGD), a traditional Chinese medicine formulated by Zhang Zhongjing in the Eastern Han Dynasty, has been effectively used in clinical practice to treat the symptoms of Taiyang and Shaoyang disorders, including fever, headache, and psychiatric disorders. AIM OF THE STUDY: To demonstrate the protective effects of CGD in an animal model of anti-NMDAR encephalitis and explore the potential mechanisms involved. MATERIALS AND METHODS: UHPLC-HRMS was used to identify CGD's chemical components and serum metabolomic profiles. Network pharmacology and molecular docking were performed to predict potential targets of CGD for the treatment of anti-NMDAR encephalitis. The effect of CGD on anti-NMDAR encephalitis was evaluated using a mouse model induced by patients' antibodies. Behavioral tests were performed to assess cognitive impairment and schizophrenia-like behaviors. The effect of CGD on the cell-surface NMDAR GluN1 subunit in cultured neurons treated with patient antibodies was detected by immunofluorescence. Golgi staining was used to observe morphological changes in hippocampal dendrites. The expression of NMDAR-interacting proteins and various neuroreceptors in the hippocampus were examined to validate the targets predicted using network pharmacology and molecular docking. RESULTS: CGD alleviated cognitive, memory, and sensorimotor gating deficits in mice treated with anti-NMDAR encephalitis patients' antibodies. Further experiments demonstrated the effect of CGD in preventing NMDAR reduction both in vitro and in vivo. Meanwhile, CGD regulated NMDAR-interacting proteins and dopamine receptors but did not affect hippocampal dendritic morphology and synaptic density. Additionally, CGD modifies metabolic pathways associated with anti-NMDAR encephalitis and other neurological and psychiatric disorders. CONCLUSIONS: CGD exhibited protective effects against anti-NMDAR encephalitis by mitigating the antibody-induced reduction in NMDAR and NMDAR-interacting proteins.

Acute waterborne cadmium exposure induces liver ferroptosis in Channa argus.

The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe2+, ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.

Identification of serum metabolites associated with aristolochic acid nephropathy severity and insights into the underlying mechanism.

Aristolochic acid nephropathy (AAN) is a rapidly progressive kidney disease caused by medical or environmental exposure to aristolochic acids (AAs). This study aimed to identify serum metabolites associated with the severity of acute AAN and investigate the underlying mechanisms. Male C57BL/6 mice were treated with vehicle and 3 doses of aristolochic acid I (AAI) (1.25, 2.5, and 5 mg/kg/d) for 5 days by intraperitoneal injection. The results showed that AAI dose-dependently increased blood urea nitrogen (BUN) and serum creatinine (Scr) levels and renal pathological damage. Non-targeted metabolomics revealed that differences in serum metabolite profiles from controls increased with increasing AAI doses. Compared with the control group, 56 differentially expressed metabolites (DEMs) that could be affected by all 3 doses of AAI were obtained. We further identified 13 DEMs whose abundance significantly correlated with Scr and BUN levels and had good predictive values for diagnosing AAI exposure. Among the 13 DEMs, lipids and lipid-like molecules constituted the majority. Western blotting found that AAI suppressed renal fatty acid oxidation (FAO)-related enzymes expression. In conclusion, these findings provided evidence for developing biomarkers for monitoring AAs exposure and AAN diagnosis and indicated activation of FAO as a potential direction for the treatment of AAN.