Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective To discuss the feasibility and safety of simultaneous bilateral adrenal vein sampling(AVS)using two 4F-MPA1 catheters via right elbow vein access.Methods A total of 51 consecutive patients with primary aldosteronism,who received simultaneous bilateral AVS using two 4F-MPA1 catheters(one of the two catheters was shaped into pig tail figure)via right elbow vein access at Xiangyang Municipal Central Hospital between October 2021 and October 2022,were enrolled in this study.The used catheter,the success rate of simultaneous bilateral AVS,and the incidence of complications rate were calculated.Results The 4F-MPA1 catheter was used for all of the right AVS,while a specially shaped 4F-MPA1 catheter was used for the main trunk vein AVS of the left adrenal gland and the central vein AVS of the left adrenal gland.The success rate of simultaneous bilateral AVS was 92.2%(47/51).Adrenal hematoma occurred in one patient(1.96%).Conclusion The technique of simultaneous bilateral AVS using two 4F-MPA1 catheters via right elbow vein access is simple to operate,less traumatic,and clinically safe and feasible.However,due to the small sample used in this study,the clinical value of this technique still needs further investigation and verification.

Objective:To explore the current situation and influencing factors of quality of life of septic patients in intensive care unit (ICU) after discharge, and to provide theoretical basis for clinical early psychological intervention and continuity of care.Methods:A prospective observational study was conducted. The septic patients who were hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University and discharged with improvement from January 1 to December 31, 2022 were selected as the research objects. The demographic information, basic diseases, infection site, vital signs at ICU admission, severity scores of the condition within 24 hours after ICU admission, various biochemical indexes, treatment process, and prognostic indexes of all the patients were recorded. All patients were assessed by questionnaire at 3 months of discharge using the 36-item short-form health survey scale (SF-36 scale), the activities of daily living scale (ADL scale), and the Montreal cognitive assessment scale (MoCA scale). Multiple linear regression was used to analyze the factors influencing the quality of life of septic patients after discharge from the hospital.Results:A total of 200 septic patients were discharged with improvement and followed up at 3 months of discharge, of which 150 completed the questionnaire. Of the 150 patients, 57 had sepsis and 93 had septic shock. The total SF-36 scale score of septic patients at 3 months of discharge was 81.4±23.0, and the scores of dimensions were, in descending order, role-emotional (83.4±23.0), mental health (82.9±23.6), bodily pain (82.8±23.3), vitality (81.6±23.2), physical function (81.4±23.5), general health (81.1±23.3), role-physical (79.5±27.0), and social function (78.8±25.2). There was no statistically significant difference in the total SF-36 scale score between the patients with sepsis and septic shock (82.6±22.0 vs. 80.7±23.6, P > 0.05). Incorporating the statistically significant indicators from linear univariate analysis into multiple linear regression analysis, and the results showed that the factors influencing the quality of life of septic patients at 3 months after discharge included ADL scale score at 3 months after discharge [ β= 0.741, 95% confidence interval (95% CI) was 0.606 to 0.791, P < 0.001], length of ICU stay ( β= -0.209, 95% CI was -0.733 to -0.208, P = 0.001), duration of mechanical ventilation ( β= 0.147, 95% CI was 0.122 to 0.978, P = 0.012), total dosage of norepinephrine ( β= -0.111, 95% CI was -0.044 to -0.002, P = 0.028), mean arterial pressure (MAP) at ICU admission ( β= -0.102, 95% CI was -0.203 to -0.007, P = 0.036) and body weight ( β= 0.097, 95% CI was 0.005 to 0.345, P = 0.044). Conclusions:The quality of life of patients with sepsis at 3 months after discharge is at a moderately high level. The influencing factors of the quality of life of patients with sepsis at 3 months after discharge include the ADL scale score at 3 months after discharge, the length of ICU stay, the duration of mechanical ventilation, the total dosage of norepinephrine, MAP at ICU admission and body weight, and healthcare professionals should enhance the treatment and care of the patients during their hospitalization based on the above influencing factors, and pay attention to early psychological intervention and continued care for such patients.

Objective:To explore the relationship between the expression levels of beclin1, hypoxia-induced-factor-1 α (HIF-1α) and the efficacy of trastuzumab on human epidermal growth factor receptor 2 (HER2) positive breast cancer.Methods:Clinical data of 90 patients with HER2-positive breast cancer treated with trastuzumab after surgery in our hospital from Mar. 2021 to May. 2023 were collected. The expression levels of Beclin1 and HIF-1α in all patients were determined by immunohistochemistry. Patients were divided into the effective group and the ineffective group according to chemotherapy efficacy. Clinical data and expression levels of Beclin1 and HIF-1α were compared between the two groups, and the relationship between expression levels of Beclin1, HIF-1α and the efficacy was evaluated by Logistic regression analysis.Results:In 90 patients with HER2-positive breast cancer treated with trastuzumab, the effective rate was 72.22% (65/90) and the ineffective rate was 27.78% (25/90). Beclin1 had no expression, low expression and high expression in 11, 26 and 53 HER2-positive breast cancer patients after treatment, which were better than the 23, 29 and 38 cases before treatment; HIF-1α had no expression in 53 cases, low expression in 8 cases and high expression in 29 cases, which was better than that before treatment in 32 cases, 17 cases and 41 cases ( Z=6.50, 7.31, P<0.05). The proportion of TNM stages I-II and histological grade 3 in the effective group was 83.08% (54/65) and 87.69% (57/65), higher than that in the ineffective group [60.00% (15/25) and 64.00% (16/25) ( χ2=5.38, 6.62, P<0.05). The high expression of Beclin1 in the effective group was higher [53.85% (35/65) vs. 12.00% (3/25) ], and the high expression of HIF-1α was lower [36.92% (24/65) vs. 68.00% (17/25) ] ( Z=16.76, 7.59, P<0.05). Logistic regression analysis showed that TNM stage, histological grade, Beclin1 expression level and HIF-1α expression level were all related factors affecting the curative effect of HER2-positive breast cancer patients ( P<0.05) . Conclusions:Beclin1 and HIF-1α expression levels are related to the efficacy of trastuzumab in the treatment of HER2-positive breast cancer, and can be used as a predictor of the efficacy of patients.

Objective:To investigate the risk factors of lower extremity deep venous thrombosis (LEDVT) in patients with sepsis during hospitalization in intensive care unit (ICU), and to construct a nomogram prediction model of LEDVT in sepsis patients in the ICU based on the critical care scores combined with inflammatory markers, and to validate its effectiveness in early prediction.Methods:726 sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from January 2015 to December 2021 were retrospectively included as the training set to construct the prediction model. In addition, 213 sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from January 2022 to June 2023 were retrospectively included as the validation set to verify the performance of the prediction model. Clinical data of patients were collected, such as demographic information, vital signs at the time of admission to the ICU, underlying diseases, past history, various types of scores within 24 hours of admission to the ICU, the first laboratory indexes of admission to the ICU, lower extremity venous ultrasound results, treatment, and prognostic indexes. Lasso regression analysis was used to screen the influencing factors for the occurrence of LEDVT in sepsis patients, and the results of Logistic regression analysis were synthesized to construct a nomogram model. The nomogram model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve, clinical impact curve (CIC) and decision curve analysis (DCA).Results:The incidence of LEDVT after ICU admission was 21.5% (156/726) in the training set of sepsis patients and 21.6% (46/213) in the validation set of sepsis patients. The baseline data of patients in both training and validation sets were comparable. Lasso regression analysis showed that seven independent variables were screened from 67 parameters to be associated with the occurrence of LEDVT in patients with sepsis. Logistic regression analysis showed that the age [odds ratio ( OR) = 1.03, 95% confidence interval (95% CI) was 1.01 to 1.04, P < 0.001], body mass index (BMI: OR = 1.05, 95% CI was 1.01 to 1.09, P = 0.009), venous thromboembolism (VTE) score ( OR = 1.20, 95% CI was 1.11 to 1.29, P < 0.001), activated partial thromboplastin time (APTT: OR = 0.98, 95% CI was 0.97 to 0.99, P = 0.009), D-dimer ( OR = 1.03, 95% CI was 1.01 to 1.04, P < 0.001), skin or soft-tissue infection ( OR = 2.53, 95% CI was 1.29 to 4.98, P = 0.007), and femoral venous cannulation ( OR = 3.72, 95% CI was 2.50 to 5.54, P < 0.001) were the independent influences on the occurrence of LEDVT in patients with sepsis. The nomogram model was constructed by combining the above variables, and the ROC curve analysis showed that the area under the curve (AUC) of the nomogram model for predicting the occurrence of LEDVT in patients with sepsis was 0.793 (95% CI was 0.746 to 0.841), and the AUC in the validation set was 0.844 (95% CI was 0.786 to 0.901). The calibration curve showed that its predicted probability was in good agreement with the actual probabilities were in good agreement, and both CIC and DCA curves suggested a favorable net clinical benefit. Conclusion:The nomogram model based on the critical illness scores combined with inflammatory markers can be used for early prediction of LEDVT in ICU sepsis patients, which helps clinicians to identify the risk factors for LEDVT in sepsis patients earlier, so as to achieve early treatment.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective:To summarize the genotype and clinical characteristics of chylomicron retention disease (CMRD) caused by secretion associated Ras related GTPase 1B (SAR1B) gene variations.Methods:Clinical data and genetic testing results of 2 children with CMRD treated at Children′s Hospital of Fudan University and Jiangxi Provincial Children′s Hospital from May 2022 to July 2023 were summarized. To provide an overview of the clinical and genetic characteristics of CMRD caused by SAR1B gene variations, all of the literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to January 2024) with "chylomicron retention disease" "Anderson disease" or "Anderson syndrome" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of CMRD caused by SAR1B gene variations.Results:One 11-year-old boy and one 4-month-old girl with CMRD. Both patients had lipid malabsorption, failure to thrive, decreased cholesterol, elevated transaminase and creatine kinase, and Vitamin E deficiency, with homozygous variations (c.224A>G) and compound heterozygous variations (c.224A>G and c.554G>T) in SAR1B gene, respectively. Case 1 was followed up for over a month, and he still occasionally experienced lower limb muscle pain. Case 2 was followed up for more than a year, and her had caught up to normal levels. Both patients had no other significant discomfort. Literature search retrieved 0 Chinese literature and 22 English literatures. In addition to the 2 cases reported in this study, a total of 51 patients were identified as CMRD caused by SAR1B gene variations. Twenty-one types of SAR1B variants 10 missense, 4 nonsense, 3 frameshift, 1 in-frame deletion, 1 splice, 1 gross deletion, and 1 gross insertion-deletion were found among the 51 CMRD cases. Among all the patients, 49 cases had lipid malabsorption (43 cases had diarrhea or fatty diarrhea, 17 cases had vomiting, and 12 cases had abdominal distension), 45 cases had lipid soluble Vitamin deficiency (43 cases had Vitamin E deficiency, 10 cases had Vitamin A deficiency, 9 case had Vitamin D deficiency, and 5 cases had Vitamin K deficiency), 35 cases had failure to thrive, 32 cases had liver involvement (32 cases had elevated transaminases, 5 cases had fatty liver, and 3 cases had hepatomegaly), 29 cases had white small intestinal mucosa under endoscopy, and 17 cases had elevated creatine kinase, 14 cases had neuropathy, 5 cases had ocular lesions, 2 cases had acanthocytosis, 1 case had decreased cardiac ejection fraction, and 1 case was symptom-free.Conclusions:Early infancy failure to thrive and lipid malabsorption are common issues for CMRD patients. The laboratory tests are characterized by hypocholesterolemia with or without fat-soluble Vitamin deficiency, elevated liver enzymes and (or) creatine kinase. Currently, missense variations are frequent among the primarily homozygous SAR1B genotypes that have been described.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.

Objective: The aging demographic landscape worldwide portends a heightened prevalence of neurodegenerative disorders. Foremost among these is Alzheimer’s disease (AD), the foremost cause of dementia in older adults. The shortage of efficacious therapies and early diagnostic indicators underscores the imperative to identify non-invasive biomarkers for early detection and disease monitoring. Recently, blood metabolites have emerged as promising candidates for AD biomarkers. Methods: Leveraging nuclear magnetic resonance (NMR) spectroscopy on plasma specimens, we conducted a cross-sectional study encompassing 35 AD patients and 35 age-matched healthy controls. Cognitive function was evaluated using the mini-mental state examination in all participants, followed by peripheral blood sample collection. We utilized univariate and multivariate analyses to perform targeted lipidomic profiling via NMR spectroscopy. Results: Our study revealed significant differences in the expression profiles of low-density lipoprotein-associated subfractions in females and high-density lipoprotein-associated subfractions in males between AD patients and healthy controls (all p<0.05). However, there was no significant metabolite overlap between males and females. Furthermore, receiver operating characteristic curve analysis demonstrated that the combination of lipid metabolites had good diagnostic values (all area under the curve>0.70; p<0.05). Conclusion Our findings suggest that the blood plasma samples using NMR hold promise in distinguishing between AD patients and healthy controls, with significant clinical implications for advancing AD diagnostic methodologies.