Multiple extreme overdose of antipsychotics with minimal side effects: A case report.

Key Clinical Message: Antipsychotic drug treatment is a commonly used therapeutic strategy in the field of psychiatry. Rational and standardized use of antipsychotics is crucial in clinical practice, and excessive use of antipsychotics may lead to severe toxic reactions. Thus, attention should be given to the monitoring of drug concentration and examination of organ function. Abstract: Excessive use of antipsychotics can cause a variety of adverse effects, including dysfunction of the liver and other organs. Liver cytochrome P450 (CYP450) enzymes play an important role in the metabolism of antipsychotics, and metabolizer types of CYP450 enzymes may influence the therapeutic effects. In this case report, we introduced a 52-year-old woman with a 23-year history of schizophrenia who took excessive doses of multiple antipsychotics and other herbal preparations for nearly 2 years, with poor response to treatment and minor side reactions to the antipsychotics. Pharmacogenomic examination showed that this patient was a CYP1A2 ultra-rapid metabolizer. The examination and treatment of this patient may provide a reference for the management of similar cases with poor response to an alarming tolerance for antipsychotics.

Thyroid cancer prognostic biomarker ARL4A and its relationship with immune infiltration.

BACKGROUND: Thyroid cancer (THCA) is a prevalent form of cancer with high rates of morbidity and mortality. The small GTPase ADP-ribosylation factor-like 4A (ARL4A) is integral to various cellular processes, including cytoskeletal restructuring, vesicular transport, cell migration, and neuronal development. However, the role of ARL4A as a clinical predictor, particularly its relation to immune cell infiltration in THCA, remains unclear. METHODS: A combination of experimental studies and analysis of online databases was employed to investigate ARL4A expression in THCA. Clinical and pathological data from THCA patients were compiled for a comprehensive subgroup analysis. The Kaplan-Meier and Cox regression methods were utilized to evaluate the prognostic significance of ARL4A in THCA patients. Finally, the "Cancer Genome Atlas" was analyzed to explore the correlation between immune cell infiltration, ARL4A expression, and their joint impact on prognosis. RESULTS: ARL4A exhibited low expression in THCA. An elevated ARL4A was associated with poor prognosis. Moreover, the expression of ARL4A was correlated with the age, gender, and pathological stage of THCA patients. Finally, ARL4A expression was found to be negatively correlated with immune cell infiltration and influenced the prognosis of patients through changes in the immune environment. CONCLUSION: ARL4A may serve as a potential biomarker for the diagnosis and treatment of THCA, impacting the prognosis of patients through the modulation of the immune microenvironment.

Left atrial and left ventricular strain in feature-tracking cardiac magnetic resonance for predicting patients at high risk of sudden cardiac death in hypertrophic cardiomyopathy.

Background: Sudden cardiac death (SCD) represents the most severe complication of hypertrophic cardiomyopathy (HCM). The risk stratification of SCD in patients with HCM remains a subject of ongoing debate, and the utility of left atrial (LA) and left ventricular (LV) myocardial strain for risk stratification of also SCD remains uncertain. Through use of feature-tracking cardiac magnetic resonance (FT-CMR), this study aimed to investigate the attenuation of LA and LV strain in HCM and to assess their predictive value in SCD. Methods: This retrospective and cross-sectional study included patients with HCM who underwent 3.0 T cardiac magnetic resonance (CMR) at a single institution. Feature-tracking strain analysis was conducted to obtain the strain rate (SR) and LV strain and to evaluate LV function. LA strain was measured during different functional phases including left atrial reservoir strain (LARS), LA conduit strain (LACS), and LA booster strain. All patients were categorized into high- and low-risk groups for SCD as defined by the 2020 American Heart Association/American College HCM implantable cardioverter defibrillator class of recommendation algorithm. Comparison between the two groups was conducted using the independent samples t test and the nonparametric rank sum test. Multivariate logistic regression analysis was performed to further identify the factors influencing SCD risk in HCM. Results: Compared with those in the low-risk group, patients in the high-risk group had lower left ventricular ejection fraction (LVEF), LV stroke volume index (LVSVI), and LA stroke volume index (LASVI) but a higher LV end-systolic volume index (LVESVI), LV maximum wall thickness, and late gadolinium enhancement (LGE) (P<0.001). LV strain, SR, and LA strain all showed significant differences between the high- and low-risk groups (LARS: P=0.04; LACS: P=0.02; all other P values <0.001). The LV global circumferential strain (LVGCS) had a strong negative correlation with LVEF in patients with HCM (r=-0.76; P<0.001). Multivariate analysis showed that LV global radial strain (LVGRS) and LARS could be used for categorizing the patients into the high-risk group [LVGRS: odds ratio (OR) =0.69; 95% confidence interval (CI): 0.55-0.87, P<0.001; LARS: OR =1.39; 95% CI: 1.02-1.90, P=0.03]. The combined LVGRS-LARS model exhibited a superior diagnostic value for high risk of SCD [area under the curve (AUC) =0.95; 95% CI: 0.90-1.00; P<0.001] compared to LARS alone (AUC =0.63; 95% CI: 0.51-0.76; P=0.04). Conclusions: LA and LV strain measured by FT-CMR can accurately identify those patients with HCM at a high risk of SCD. This approach may prove considerably value in guiding early therapeutic intervention with implantable cardioverter-defibrillators (ICDs) to prevent adverse clinical outcomes.

Aristolochic acid induces acute kidney injury through ferroptosis.

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

Effect of propranolol on pharmacokinetics of clozapine in schizophrenic patients: a meta-analysis.

PURPOSE: Clozapine is the effective therapy for treatment-refractory schizophrenia. However, the use of clozapine is limited by its adverse effects. As propranolol is frequently used for the prevention and treatment of clozapine-induced tachycardia, we performed a meta-analysis to evaluate the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients. METHODS: We included 16 retrospective studies on the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients, with data from both generic and brand name treatment phases in eight clozapine bioequivalence studies conducted in a single center in China from 2018 to 2022. Review Manager 5.4 was used for meta-analysis of the included studies. RESULTS: The SMDs with 95% CIs of AUC0-12, Cmax,ss, C, and C were calculated to be 0.44 (0.23, 0.64), 0.40 (0.20, 0.61), 0.43 (0.22, 0.63), and 0.44 (0.23, 0.64), respectively. These findings proved that combination with propranolol would increase the systemic exposure of clozapine. T1/2 of clozapine was significantly longer in the presence of propranolol than in the absence of propranolol (SMD = 0.32, 95% CI [0.12, 0.52], p = 0.002). There was no statistically significant difference for T of clozapine in the presence or absence of propranolol (SMD = - 0.05, 95% CI [- 0.25, 0.15], p = 0.63). CONCLUSION: The combination with propranolol could significantly increase systemic exposure and extended T1/2 of clozapine, and thus need to be considered in prescribing decisions.

The Feasibility of Left Ventricular Strain and Strain Rate for Evaluating Patients With Risk Factors of Sudden Cardiac Death in Hypertrophic Cardiomyopathy by Feature Tracking Cardiac Magnetic Resonance.

Sudden cardiac death (SCD) represents the most severe complication of hypertrophic cardiomyopathy (HCM). However, the relation between strain, strain rate (SR), and risk factors in SCD risk stratification remains elusive. The study aimed to assess the attenuation of strain and SR in HCM by feature tracking cardiac magnetic resonance. All strain and SRs were obtained automatically by feature tracking, with manual adjustment of endocardial and epicardial borders. Strain indicators included left ventricular global longitudinal, circumferential, global radial strain (GRS), peak diastolic-longitudinal, circumferential, and radial SR. Patients were categorized into high-risk and low-risk groups for SCD based on the 2020 American Heart Association/American College HCM risk-SCD model. The correlation between strain/SR and SCD risk factors was assessed through Spearman correlation analysis. Furthermore, a multivariate logistic regression analysis was conducted to explore the factors that influence SCD risk in HCM patients. A total of 105 HCM patients were analyzed in this study, including 38 patients in the high-risk group, and 67 patients in the low-risk group. Compared with the low-risk group, the high-risk group exhibited significantly worse strain and SR (p <0.001). Furthermore, both circumferential and GRS and SR exhibited meaningful associations with risk factors for SCD. Additionally, GRS emerged as an independent risk factor for predicting heightened SCD risk in HCM patients (p <0.001). In conclusion, left ventricular strain and SR based on feature tracking-cardiac magnetic resonance can be evaluated for SCD risk and are strongly associated with SCD risk factors.

Increased circulating cell-free mitochondrial DNA in plasma of first-diagnosed drug-naïve bipolar disorder patients: A case-control and 4-week follow-up study.

BACKGROUND: The study of clinical biological indicators in bipolar disorder (BD) is important. In recent years, basic experiments have associated the pathophysiological mechanism of BD is related to mitochondrial dysfunction, but few clinical studies have confirmed this finding. OBJECT: The present study aimed to evaluate whether plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels, which can represent the degree of mitochondrial damage in vivo, are altered in patients with BD in early onset and during treatment compared with controls. METHOD: A total of 75 first-diagnosed drug-naive patients with BD and 60 HCs were recruited and followed up for 1 month. The clinical symptoms were assessed using HAMD, HAMA, and YMRS, and ccf-mtDNA levels were measured by qPCR before and after drug treatment in BD. RESULT: (1) The plasma ccf-mtDNA levels in first-diagnosed drug-naive patients with BD increased compared with those in HCs (p = 0.001). (2) Drug treatment for 1 month can decrease the expression of ccf-mtDNA in BD (p < 0.001). (3) No significant correlation was observed between the changes in ccf-mtDNA levels and the improvement of clinical symptoms in BD after drug treatment. CONCLUSION: The plasma ccf-mtDNA level was increased in BD, and decreased after pharmacological treatment. These outcomes suggested that plasma ccf-mtDNA level is likely to be sensitive to the drug response in BD, and mitochondrial pathway is a potential target for further therapy.

Osteoporosis and low bone mass among schizophrenia and bipolar disorder: A cross-sectional study with newly diagnosed, drug-naïve subjects.

BACKGROUND: A growing body of data shows that schizophrenia (SCZ) and bipolar disorder (BD) have substantial metabolic risks; however, few studies have focused on bone metabolism. This study aimed to assess the prevalence and associated influencing factors of low bone mass and osteoporosis in SCZ and BD before pharmacological effects occur. METHODS: 108 healthy controls (HCs) and drug-naïve individuals with SCZ (n = 56) and BD (n = 130) had their lumbar spine (L1-L4) and left femur (Neck/Trochanter/Ward's triangle) bone mineral density (BMD) determined using dual-energy X-ray absorptiometry. Besides, we measured bone turnover markers (BTMs) levels, including procollagen I N-terminal propeptide, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen in different groups. RESULTS: Individuals with SCZ and BD had significantly lower BMD and significantly higher prevalence of low bone mass and osteoporosis compared with HCs. In the main observation regions of the total lumbar (F = 18.368, p < 0.001) and left femur (F = 14.790, p < 0.001), BMD was lower in individuals with SCZ and BD than HCs, with SCZ showing lower BMD than BD. The osteocalcin (H = 11.421, p = 0.003) levels were significantly higher in SCZ and BD than HCs. Binary regression analysis showed that SCZ or BD was an independent risk factor for low bone mass and osteoporosis. In addition, sex, age, and BTMs also influenced the occurrence of low bone mass and osteoporosis. LIMITATIONS: Cross-sectional study. CONCLUSION: The results findings of the study might contribute to our understanding of the increased risk of bone metabolism in SCZ and BD. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR1900021379.

Higher-order sensorimotor circuit of the whole-brain functional network involved in pruritus regulation in atopic dermatitis.

BACKGROUND: Little is known about the neural mechanisms underlying pruritus regulation in Atopic dermatitis (AD). OBJECTIVE: To investigate the functional changes of the resting-state whole brain network of AD participants and the mechanisms by which they were involved in pruritus regulation. METHOD: Based on the functional magnetic resonance imaging data from 19 AD participants and 37 healthy controls (HC), a graph-theoretical measure of degree centrality (DC) conjoined with a voxel-level seed-based functional connectivity (FC) method was used to identify abnormal higher-order nodes and the functionally relevant circuit in AD participants compared to healthy controls (HC). RESULTS: Of 64 participants screened, 19 AD participants (12M/7F, median [IQR] age, 27 [14] years) and 36 HCs (13M/23F, median [IQR] age, 20 [1] years) were enrolled. DC values of the left superior frontal gyrus (LSFG) increased in AD participants and exhibited a negative correlation with the SCORAD score (r = -0.561, p = 0.012) compared with HC. In the FC analysis with LSFG as the seed, FC values of several sensory and motor regions increased in AD participants, highly overlapping with the anatomical distribution of the inferior fronto-occipital fascicle (IFOF). AD participants with severe pruritus exhibited lower levels of DC (T = -2.316, p = 0.033) and FC between the LSFG and left insula (T = -2.203, p = 0.042) than those with mild-to- moderate pruritus. CONCLUSIONS AND RELEVANCE: LSFG was involved in pruritus regulation in AD by forming a high-order sensorimotor circuit through the IFOF, a white matter fascicle that proved to provide multimodal integration in motor control and sensory information processing. These results offer more mechanism-guided treatment targets for severe pruritus in AD.

The centre-calculated cutoff value is better for identifying fast peritoneal solute transfer of patients on peritoneal dialysis than the traditional value: a retrospective cohort study.

Background: The mean 4-h dialysate to plasma ratio of creatinine (4-h D/Pcr) is a vital cutoff value for recognizing the fast peritoneal solute transfer rate (PSTR) in patients on peritoneal dialysis (PD); however, it shows a noticeable centre effect. We aimed to investigate our centre-calculated cutoff value (CCV) of 4-h D/Pcr and compare it with the traditional cutoff value (TCV) (0.65). Methods: In this study, we enrolled incident PD patients at our centre from 2008 to 2019, and divided them into fast or non-fast PSTR groups according to baseline 4-h D/Pcr-based CCV or TCV. We compared the efficiency of the fast PSTR recognized by two cutoff values in predicting mortality, ultrafiltration (UF) insufficiency and technical survival. Results: In total, 1905 patients were enrolled, with a mean 4-h D/Pcr of 0.71 ± 0.11. Compared with TCV (0.65), CCV (0.71) showed superiority in predicting mortality of PD patients [hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.02-1.59 vs HR 1.24, 95% CI 0.97-1.59]. The odds ratio (OR) of the fast PSTR in centre classification was slightly higher than traditional classification in predicting UF insufficiency (OR 1.67, 95% CI 1.25-2.24 vs OR 1.60, 95% CI 1.15-2.22). Additionally, the restricted cubic splines 4-h D/Pcr has an S-shaped association with mortality and UF insufficiency, and the inflection points of 4-h D/Pcr were 0.71 (equal to CCV). Conclusions: The CCV of 4-h D/Pcr for identifying fast PSTR was 0.71. It was superior to TCV in predicting mortality and UF insufficiency.

Incremental peritoneal dialysis and survival outcomes: a propensity-matched cohort study.

BACKGROUND: The advantages of an incremental dialysis start are not fully clear. We aimed to evaluate the association of incremental initiation of peritoneal dialysis with mortality. METHODS: Incident peritoneal dialysis patients with a catheter placed at our hospital between 2008 and 2017 were included. All patients were followed up until December 31, 2019. Patients were categorized into different groups according to the initial daily dialysis exchanges, and were matched at a ratio of 1:2 with propensity score matching. Multiple variables including age, sex, residual kidney function, urine volume, hemoglobin, serum albumin and other important variables were included for the matching. Primary outcomes were all-cause and cardiovascular mortality. RESULTS: A total of 1315 patients with a mean age of 45.9 years were enrolled. The mean glomerular filtration rate was 4.32 ml/min/1.73 m2 at start of dialysis. Two hundred eighty-five patients in the incremental group and 502 in the full dose group were matched for age, sex, residual kidney function, urine volume, hemoglobin, serum albumin and other important variables. Patient survival and cardiovascular event-free survival were similar between the two groups. However, during the first 6 years of peritoneal dialysis, patients in the incremental group had better survival (P = 0.011) and cardiovascular event-free survival (P = 0.044) than the full dose group, while such advantages disappeared when dialysis vintage became longer. Further analysis showed that the incremental group (vs full dose dialysis) had a 39% lower risk (95% CI 0.42-0.90, P = 0.012) of all-cause mortality and a 41% decreased risk (95% CI 0.35-0.99, P = 0.047) of cardiovascular mortality during the first 6 years of dialysis. Additionally, the cumulative hazard for anuria was significantly lower in the incremental group versus the full dose group (P = 0.006). CONCLUSIONS: Our study shows a time-related survival advantage for incremental peritoneal dialysis patients, suggesting that an incremental regimen for starting peritoneal dialysis is feasible and is not associated with worse outcomes. Graphical Abstract presenting schematically the measurements of the solvation response function by processing the relevant streak camera images and the time-correlated photon counting (TCSPC) data and appropriately combining them together.

Single-cell immune profiling reveals broad anti-inflammation response in bipolar disorder patients with quetiapine and valproate treatment.

Bipolar disorder (BD) is a common mental disorder characterized by manic and depressive episodes. Mood disorders have been associated with immune dysfunction. The combination of quetiapine and valproate has shown positive effects in treating BD, but the impact on immune dynamics remains less understood. Using single-cell RNA sequencing, we observed that B cells exhibited downregulation of inflammation-related genes, while pro-inflammatory mast and eosinophil cells decreased following treatment. Ribosomal peptide production genes were found to be reduced in both B and T cells after treatment. Additionally, our findings suggest that the combined therapy effectively alleviates inflammation by reducing myloid-mediated immune signaling pathways. This study provides valuable insights into the immune atlas and uncovers a potential mechanism for immune disorder alleviation in patients with BD treated with quetiapine and valproate.

Prevalence and characteristics of polycystic ovarian syndrome in patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is frequently accompanied by endocrine disturbances. We compared the prevalence of polycystic ovary syndrome (PCOS) and related reproductive disorders between drug-naïve BD patients and matched healthy controls (HCs) and between drug-naïve BD patients and BD patients with long-term medication, as well as the clinical metabolic correlates among BD patients. METHODS: 72 drug-naïve BD patients, 98 HCs, and 72 BD patients with long-term medication were recruited in the study. Menstruation was recorded, reproductive hormone levels and metabolic indicators were measured, and a pelvic ultrasound examination was performed via transvaginal sensor for each participant. PCOS was defined using the Rotterdam criteria. RESULTS: After controlling for demographic variables, drug-naïve BD patients presented higher rates of PCOS than the HCs (OR: 3.02, 95 % CI: 1.09-8.36). Regression analysis showed that long-term treatment with valproate (OR: 3.89, 95 % CI: 1.13-13.37), age (OR: 0.37, 95 % CI: 0.14-0.95), and insulin resistance index (OR: 1.73, 95 % CI: 1.10-12.71) were correlated with PCOS in BD patients. CONCLUSIONS: Drug-naïve BD patients are susceptible to developing PCOS, and valproate is correlated with increased occurrence and development of PCOS. Therefore, PCOS in BD patients, especially those who use valproate, needs to be investigated and monitored closely by medical personnel.

The feasibility of incremental peritoneal dialysis for older patients on peritoneal dialysis.

Background: This study was performed to investigate the feasibility of incremental peritoneal dialysis (iPD) in older patients. Methods: In this retrospective cohort study, we enrolled peritoneal dialysis (PD) patients with age ≥ 60 years old at our center from 2008 to 2017. The patients were divided into two groups based on the daily PD exchanges: iPD group (≤3 × 2 L exchanges), and full dose group (≥4 × 2 L exchanges). Kaplan-Meier curves and multivariate Cox regression models were applied to evaluate the risks of anuria and mortalities between groups. Results: A total of 238 patients (186 in full dose group and 52 in iPD group) were enrolled. The mean age was 67.8 ± 5.7 years, and 45.8% were females. The baseline glomerular filtration rate was 4.15 ± 2.39 mL/min/1.73 m2 . Multivariate Cox regression models showed that patients in the iPD group patients had significantly decreased risk of anuria (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.81; p = 0.008), and all-cause mortality (HR, 0.59; 95% CI, 0.36-0.98; p = 0.04). Additionally, the incidence of peritonitis was significantly lower in the iPD group than that in the full dose group (0.115 vs. 0.197 episodes per person-year, p = 0.03) during the 36 months of PD commencement. Conclusion: Older patients with iPD were independently associated with better preservation of residual kidney function and survival outcomes. Moreover, iPD regimens are also associated with reduced incidence of peritonitis. The iPD strategy might offer a feasible option for older patients.

Lupus Recipe inhibits cGVHD-induced lupus nephritis in mice and promote renal LC3-associated autophagy.

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). The chronic graft versus host disease (cGVHD) mouse model is a well-established model of SLE. LC3-associated autophagy plays a critical role in extracellular particle clearance, including pathogens and apoptotic cells. Lupus Recipe (LR) is a Chinese herbal compound that has been proven to be effective in treating SLE. In the study, we investigated the protective effects of LR or LR combined with prednisone on cGVHD mouse model and LC3-associated autophagy in the kidney. The mice were subjected to six groups. The LR treatment group received LR at the dosage of 1.15 and 2.3 g/kg/day, respectively. The corticosteroid treatment group received prednisone at a dosage of 5 mg/kg/day. The combination treatment group received LR at a dosage of 2.3 g/kg/day, and prednisone at 2.5 mg/kg/day. LR treatment reduced proteinuria and serum triglyceride levels, as well as spleen weight. LR also alleviated pathologic damage and immunoglobulin G deposition in the kidney. LR combined with a low dose of prednisone significantly improved kidney function and decreased serum triglyceride, total cholesterol, and spleen weight. In addition, combination treatment relieved kidney injury more effectively than LR alone. Western blot revealed that LR treatment or LR combined with prednisone increased the LC3-associated autophagy protein of Rubicon and Nox2, as well as LC3I levels in the kidney tissues. In conclusion, LR inhibited the manifestation of cGVHD-induced LN, which may attribute to the increased levels of LC3-associated autophagy.

Association between uric acid and cognitive dysfunction: A cross-sectional study with newly diagnosed, drug-naïve with bipolar disorder.

BACKGROUND: Cognitive impairment is one of the major symptoms of individuals with bipolar disorder (BD). Purine system disorders may play an important role in cognitive dysfunction. So far, the relationship between cognitive deficits and purinergic metabolism in BD has been seldom discussed in previous studies. This study aims to explore its relevance and potential biological mechanisms. METHODS: In this cross-sectional study, 205 first time diagnosed drug-naive individuals with BD and 97 healthy volunteers were recruited. The uric acid(UA) level was measured using automatic biochemical analyzer, and cognitive function was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Stroop color-word test. In addition, general information and clinical symptoms were collected and evaluated. RESULTS: In this study, the UA level of BD group (U = 8475.000, p = 0.038) was found to be significantly higher than that of the healthy controls, but the scores of RBANS (t = -11.302, p < 0.001) and Stroop color-word test (t = -6.962, p < 0.001) were significantly lower than that of the healthy controls. In gender subgroup analysis, females had lower UA level and higher RBANS scores. In correlation analysis, the cognitive function of individuals with BD was found to present a significant negative correlation with UA level in attention (r = -0.23, p = 0.001) and delayed memory(r = -0.16, p = 0.022). LIMITATIONS: This is a cross-sectional design. CONCLUSION: Elevated UA levels may be a potential mechanism of cognitive impairment in BD. This provides a new possible strategy for the prevention and treatment of cognitive impairment in BD.

Mesenteric elasticity assessed by shear wave elastography and its relationship with peritoneal function in peritoneal dialysis patients.

Background: We evaluated the mesenteric elasticity in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using shear wave elastography (SWE) and investigated its relationships with peritoneal function. Methods: Patients were recruited in our peritoneal dialysis (PD) centre between 15 July 2019 and 31 December 2021 and followed up to 31 March 2022. Twelve chronic kidney disease (CKD) patients and nineteen healthy people were included as controls. Correlation, linear regression and Cox regression analyses were applied. Results: Of the 218 PD patients, 104 (47.8%) were male. Their mean age was 48.0 ± 13.2 years and the median PD duration was 59.0 months [interquartile range (IQR) 17.0-105]. The median mesenteric SWE value was 8.15 kPa (IQR 5.20-16.1). The mesenteric SWE values of patients with a PD duration of <3 months [5.20 kPa (IQR 3.10-7.60)] were not significantly different from those of CKD patients [4.35 kPa (IQR 2.63-5.20), P = .17] and healthy controls [3.60 kPa (IQR 2.90-5.10), P = .13] but were lower than those of patients with a PD duration of 3 months-5 years [6.40 kPa (IQR 4.10-10.5), P < .001], 5-10 years [11.9 kPa (IQR 7.40-18.2), P < .001] and >10 years [19.3 kPa (IQR 11.7-27.3), P < .001]. Longer PD duration (ß = 0.58, P < .001), high effluent interleukin-6 (ß = 0.61, P = .001) and low effluent cancer antigen 125 (ß = -0.34, P = .03) were independently associated with low mesenteric elasticity. The mesenteric SWE value was independently correlated with the dialysate:plasma creatinine ratio (ß = 0.39, P = .01) and negatively correlated with the total daily fluid volume removed (ß = -0.17, P = .03). High mesenteric SWE values were an independent risk factor for death-censored technique failure [adjusted hazard ratio 4.14 (95% confidence interval 1.25-13.7), P = .02). Conclusions: SWE could be used to non-invasively characterize peritoneal textural changes, which were closely associated with changes in peritoneal function.

Digestion profile, antioxidant, and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis.

BACKGROUND: Novel functional polysaccharides from fungi are important nutraceuticals. An exopolysaccharide, Morchella esculenta exopolysaccharide (MEP 2), was extracted and purified from the fermentation liquor of M. esculenta. The aim of this study was to investigate its digestion profile, antioxidant capacity, and effect on the microbiota composition in diabetic mice. RESULTS: The study found that MEP 2 was stable during in vitro saliva digestion but was partially degraded during gastric digestion. The digest enzymes exerted a negligible effect on the chemical structure of MEP 2. Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. After digestion, the antioxidant ability increased as revealed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Both MEP 2 and its digested components showed strong α-amylase and moderate α-glucosidase inhibition activity, leading us to further investigate its ability to modulate the diabetic symptoms. The MEP 2 treatment ameliorated the inflammatory cell infiltration and increased the size of pancreas inlets. Serum concentration of HbA1c was significantly reduced. Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. The MEP 2 increased the diversity of the gut microbiota and modulated the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina, and several Lachnospiraceae species. CONCLUSION: It was found that MEP 2 was partially degraded during in vitro digestion. Its potential antidiabetic bioactivity may be associated with its α-amylase inhibition and gut microbiome modulation ability. © 2023 Society of Chemical Industry.

Insulin-loaded liposomes packaged in alginate hydrogels promote the oral bioavailability of insulin.

Compared to subcutaneous injections, oral administration of insulin would be a preferred route of drug administration for diabetic patients. For oral delivery, both liposomes and alginate hydrogels face many challenges, including early burst release of the encapsulated drug and poor intestinal drug absorption. Also, adhesion to the intestinal mucosa remains weak, which all result in a low bioavailability of the payload. This study reports on an alginate hydrogel loaded with liposomes for oral insulin administration. Liposomes (Lip) loaded with arginine-insulin complexes (AINS) were incorporated into a hydrogel prepared from cysteine modified alginate (Cys-Alg) to form liposome-in-alginate hydrogels (AINS-Lip-Gel). An ex vivo study proves that intestinal permeation of AINS and AINS-Lip is approximately 2.0 and 6.0-fold, respectively, higher than that of free insulin. The hydrogel retarded early release of insulin (∼30%) from the liposomes and enhanced the intestinal mucosal retention. In vivo experiments revealed that the AINS-Lip-Gel released insulin in a controlled manner and possessed strong hypoglycemic effects. We conclude that liposome-in-alginate hydrogels loaded with AINS represent an attractive strategy for the oral delivery of insulin.

High-Dose Versus Standard-Dose Intensity-Modulated Radiotherapy With Concurrent Paclitaxel Plus Carboplatin for Patients With Thoracic Esophageal Squamous Cell Carcinoma: A Randomized, Multicenter, Open-Label, Phase 3 Superiority Trial.

PURPOSE: The standard dose (SD) of definitive concurrent chemoradiotherapy (dCRT) remains 50.4 Gy in patients with esophageal cancer; a higher dose, when applied with conventional radiation therapy techniques, increases toxicities without improving survival. We investigated whether a high dose of 59.4 Gy using intensity-modulated radiation therapy (IMRT) would improve survival without increasing toxicities. METHODS: Patients with inoperable thoracic esophageal squamous cell carcinoma (SCC) referred for dCRT were randomly assigned (1:1) to high-dose (HD) IMRT (59.4 Gy) or SD IMRT (50.4 Gy). Chemotherapy consisted of 6 cycles of concurrent weekly paclitaxel and carboplatin and a maximum of 2 cycles of consolidation chemotherapy. Nutritional intervention was implemented for patients with malnutrition on the basis of nutritional screening. The primary endpoint was median overall survival (mOS). Analyses were by modified intention to treat. RESULTS: Between April 30, 2016, and April 30, 2019, 167 patients were enrolled at 9 participating centers in China. Seventy-one patients in the HD and 73 patients in the SD groups were included in the analysis; 86.8% of the patients completed radiation therapy and 70.1% received 5 or 6 cycles of concurrent chemotherapy. The median follow-up was 36.0 months. The mOS was 28.1 and 26.0 months in the HD and SD arms, respectively (P = .54). A total of 7 treatment-related deaths were observed. Grade 3 or worse treatment-related toxicities were observed in 62% and 68.5% of the patients in the HD and SD arms, respectively (P = .675). CONCLUSIONS: For patients with inoperable thoracic esophageal SCC, a dose of 59.4 Gy did not improve survival compared with the SD of dCRT using IMRT.