Psychotropic medication and hepatobiliary health: Ultrasound observations on patients with schizophrenia.

OBJECTIVE: This study sought to examine the association between antipsychotic drug use and hepatobiliary health based on serum markers and ultrasound observations on a sample of patients with schizophrenia compared to age and gender matched healthy controls. METHODS: The 120 patients with schizophrenia and 60 control subjects had their blood drawn to measure liver function tests and underwent hepatobiliary ultrasonography to determine hepatobiliary lesions. Liver function tests included total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Standardized cross-sectional images of the liver and kidneys were obtained from patients and controls, and analyses were stratified by length of taking psychotropic medication among those with schizophrenia. Liver echo attenuation coefficients, liver-kidney ratios, and liver fat content were determined. RESULTS: Psychotropic drug use was associated with greater liver burden and liver lesions in patients with schizophrenia compared to controls. The levels of TC, TG, ALT and AST in patients with schizophrenia were also all significantly higher among patients with schizophrenia. Long-term psychotropic medication was associated with increased levels of fatty liver in patients compared with controls. Levels of TC, TG, ALT and AST were all significantly higher in the long-term psychotropic medication use group than in the short-term group. Liver echo attenuation coefficient, liver-kidney ratio, and liver fat content were also higher in the long-term medication use group compared to the short-term group. CONCLUSION: Antipsychotic drug use, particularly long-term use, is associated with increased liver burden in patients with schizophrenia, impaired lipid metabolism, increased liver lesions and fat content.

Patent vitellointestinal duct with ileal prolapse in a newborn: A case report and literature review.

RATIONALE: Patent vitellointestinal duct is the most common omphalomesenteric duct anomaly to present with symptoms. PATIENT CONCERNS: A 10-day-old child presented with increase in the size of a polypoidal lesion into a large, "Y"-shaped reddish, prolapsing lesion, discharging gaseous, and fecal matter at her umbilicus. A laparoscopic exploration was performed, followed by wedge resection and anastomosis. No complications occurred during postoperative follow-up. DIAGNOSES: A patent vitellointestinal duct with ileal prolapse. INTERVENTIONS: The resection of extended intraperitoneal intestinal tube was performed. OUTCOMES: During the follow-up 3 months after surgery, the umbilical cord of the child healed well after surgery. LESSONS: Timely surgical treatment can minimize the occurrence of complications, and the overall prognosis is good after surgery.

miR-23b-3p Ameliorates LPS-Induced Pulmonary Fibrosis by Inhibiting EndMT via DPP4 Inhibition.

Acute respiratory distress syndrome is a disease triggered by severe pulmonary and systemic inflammation that may lead to fibrosis and the decline of lung function. Lung capillary endothelial-to-mesenchymal transition (EndMT) is one of the primary sources of fibroblasts in pulmonary fibrosis. The role of miRNAs as molecular markers of pulmonary fibrosis, and miRNAs as nucleic acid drugs has attracted increasing attention. To mock EndMT process, Human pulmonary microvascular endothelial cells (HPMECs) were induced with lipopolysaccharide (LPS). Similarly, LPS treatment was used to generate a mouse model of LPS-induced EndMT and pulmonary fibrosis. LPS-induced EndMT in HPMECs resulted in a significant reduction of miR-23b-3p. miR-23b-3p inhibited the interstitial transition of HPMECs, and miR-23b-3p could mediate this process via inhibiting dipeptidyl peptidase-4 (DPP4). Dual-luciferase assays confirmed the regulatory mechanism of miR-23b-3p. In our mouse model of LPS-induced pulmonary fibrosis, miR-23b-3p and a DPP4 inhibitor (sitagliptin) individually alleviated LPS-induced EndMT progression and pulmonary fibrosis, and their combined use achieved the strongest remission effect. To sum up, miR-23b-3p alleviates EndMT in pulmonary fibrosis by inhibiting the expression of DPP4.

Participation of ASK-1 in the cardiomyocyte-protective role of mechanical ventilation in a rat model of myocardial infarction.

Non-invasive positive-pressure ventilation (NIPPV) has been demonstrated to exhibit a cardioprotective function in a rat model of myocardial infarction (MI). However, the mechanism underlying NIPPV-mediated MI progression requires further investigation. We aimed to investigate the effectiveness and corresponding mechanism of NIPPV in an acute MI-induced heart failure (HF) rat model. Thirty each of healthy wild type (WT) and apoptosis signal-regulating kinase 1 (ASK-1)-deficient rats were enrolled in this study. MI models were established via anterior descending branch ligation of the left coronary artery. The corresponding data indicated that NIPPV treatment reduced the heart infarct area, myocardial fibrosis degree, and cardiac function loss in MI rats, and ameliorated apoptosis and reactive oxygen species (ROS) levels in the heart tissue. Furthermore, the expression level of ASK-1 level, a key modulator of the ROS-induced extrinsic apoptosis pathway, was upregulated in the heart tissues of MI rats, but decreased after NIPPV treatment. Meanwhile, the downstream cleavage of caspase-3, caspase-9, and PARP, alongside p38 phosphorylation and FasL expression, exhibited a similar trend to that of ASK-1 expression. The involvement of ASK-1 in NIPPV-treated MI in ASK-1-deficient rats was examined. Although MI modeling indicated that cardiac function loss was alleviated in ASK-1-deficient rats, NIPPV treatment did not confer any clear efficiency in cardiac improvement in ASK-1-knockdown rats with MI modeling. Nonetheless, NIPPV inhibited ROS-induced extrinsic apoptosis in the heart tissues of rats with MI by regulating ASK-1 expression, and subsequently ameliorated cardiac function loss and MI-dependent pathogenic changes in the heart tissue.

Identification of Potential Biomarkers of Septic Shock Based on Pathway and Transcriptome Analyses of Immune-Related Genes.

Immunoregulation is crucial to septic shock (SS) but has not been clearly explained. Our aim was to explore potential biomarkers for SS by pathway and transcriptional analyses of immune-related genes to improve early detection. GSE57065 and GSE95233 microarray data were used to screen differentially expressed genes (DEGs) in SS. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses of DEGs were performed, and correlations between immune cell and pathway enrichment scores were analyzed. The predictive value of candidate genes was evaluated by receiver operating characteristic (ROC) curves. GSE66099, GSE4607, and GSE13904 datasets were used for external validation. Blood samples from six patients and six controls were collected for validation by qRT-PCR and western blotting. In total, 550 DEGs in SS were identified; these genes were involved in the immune response, inflammation, and infection. Immune-related pathways and levels of infiltration of CD4 + TCM, CD8 + T cells, and preadipocytes differed between SS cases and controls. Seventeen genes were identified as potential biomarkers of SS (areas under ROC curves >0.9). The downregulation of CD8A, CD247, CD3G, LCK, and HLA-DRA in SS was experimentally confirmed. We identified several immune-related biomarkers in SS that may improve early identification of disease risk.

Toll-like receptor 4 promotes the inflammatory response in septic acute kidney injury by promoting p38 mitogen-activated protein kinase phosphorylation.

Septic acute kidney injury (AKI) contributes to the mortality and morbidity of sepsis patients. Toll-like Receptor 4 (TLR4) has prominent roles in septic AKI. This study investigated the functions of TLR4 in septic AKI. A septic AKI mouse model was established by cecal ligation and puncture surgery. Mouse kidney function and kidney tissue lesion were examined using corresponding kits and H&E staining. The in vitro cell model of septic AKI was established by lipopolysaccharide induction. Cell viability, inflammatory factor (TNF-α, IL-6, IL-4, IL-1ß, IL-18) levels, pyroptotic cell number changes, lactate dehydrogenase (LDH) activity, myeloperoxidase (MOP) concentration, and levels of pyroptosis-associated protein and MyD88, TRIF and p38 MAPK phosphorylation were determined by MTT, ELISA, FAM-FLICA Caspase-1 Detection kit, other corresponding kits, and Western blot. TLR4 was highly expressed in septic AKI mouse kidney tissues and human septic AKI cells. TLR4 knockdown alleviated kidney injury, increased cell viability, and reduced LDH activity and MPO concentration. TLR4 knockdown reduced cell pyroptosis by repressing p38 MAPK phosphorylation through MyD88/TRIF, suppressed pro-inflammatory factor (TNF-α, IL-6, IL-4, IL-1ß, IL-18) levels, promoted anti-inflammatory factor (IL-4) level, and reduced inflammatory response, thus playing a protective role in septic AKI. Briefly, TLR4 promoted the inflammatory response in septic AKI by promoting p38 MAPK phosphorylation through MyD88/TRIF.

Mechanical ventilation reduces myocardial injury in rats with acute heart failure by inhibiting cardiomyocyte apoptosis.

OBJECTIVE: To explore the mechanism by which mechanical ventilation improves myocardial injury in rats with acute heart failure (AHF). METHODS: Thirty-six male Sprague Dawley rats were randomized into a sham group, heart failure (HF) group, and mechanical ventilation (MV) group. The AHF rat model was established by pentobarbital perfusion under right internal jugular vein monitoring. The symptoms of heart failure, changes in hemodynamic parameters, cardiac function, N-terminal pro-B-type natriuretic peptide (NT-proBNP), oxidative stress-related indicators, myocardial apoptosis index, and expression of apoptosis-related proteins were compared in an AHF rat model with or without mechanical ventilation. RESULTS: Compared to the sham group, the hemodynamics and cardiac function of MV and HF groups were markedly reduced (P<0.05), and the serum levels of NT-proBNP of MV and HF groups were elevated (P<0.05). The levels of malondialdehyde (MDA) were lowest in the sham group, followed by the MV group, and highest in the HF group. Glutathione (GSH) and superoxide dismutase (SOD) were lowest in the HF group, inermediate in MV group, and highest in the sham group (P<0.05). Mechanical ventilation improved myocardial injury and reduced apoptosis of myocardial cells in a rat model of AHF. CONCLUSION: Mechanical ventilation in the early stage of heart failure can significantly reduce the excessive occurrence of oxidative stress in rats and significantly improve apoptosis in myocardial cells in AHF rats, so as to effectively improve the symptoms of AHF and reduce the mortality of AHF rats.

Application of antagonist regimen in patients with failed pregnancy assisted by previous long-term regimen during early follicular phase.

OBJECTIVE: To investigate the clinical application of gonadotropin-releasing hormone antagonist (GnRH-ant) in patients with failed pregnancy assisted by the previous long-term regimen during early follicular phase (EFP). METHODS: A total of 122 patients with good ovarian function and two previous failed EFP long-term assisted pregnancy were selected from the reproductive center of our hospital for study. All patients were assisted by in vitro fertilization-embryo transfer (IVF-ET) twice. According to the random number table method, the participants were divided into group A (n=61) for subcutaneous injection of gonadotropin-releasing hormone agonist (GnRH-a) and group B (n=61) for GnRH-ant, and the clinical efficacy of the two groups were observed. RESULTS: Group B presented reduced dosage and duration of Gn, increased number and probability of eggs retrieved, and increased number of 2PN, cleavage and transplantable embryos than group A (all P<0.05). Serum estradiol (E2) and luteinizing hormone (LH) levels elevated and T level decreased in group B as compared to group A (all P<0.05). There was no significant difference in follicle-stimulating hormone (FSH) indexes between the two groups (P>0.05). Endometrial thickness and mean ovarian volume (MOV, the mean volume of bilateral ovaries) were not significantly different between group A and group B before treatment (both P>0.05), while were lower in group B than in group A after treatment (both P<0.05). Group B had higher high-quality egg rate (%), fertilization rate (should have numbers here %), cleavage rate (%), high-quality embryo rate (should have numbers here %) and cumulative pregnancy rate (%) than group A (all P<0.05). The incidences of moderate OHSS, early abortion and hydrosalpinx were lower in group B than in group A (all P<0.05), while there was no evident difference between the two groups in the occurrence of severe OHSS and ectopic pregnancy (both P>0.05). CONCLUSION: GnRH-ant can improve the clinical high-quality embryo rate in patients with the previous failed EFP long-term assisted pregnancy, and reduce the occurrence of OHSS events. Compared with GnRH-a, GnRH-ant is more suitable for clinical application of controlled ovarian hyperstimulation.

Nanostructuring Synergetic Base-Stacking Effect: An Enhanced Versatile Sandwich Sensor Enables Ultrasensitive Detection of MicroRNAs in Blood.

MicroRNA (MiRNA)-based noninvasive diagnostics are hampered by the challenge in the quantification of circulating miRNAs using a general strategy. Here, we present a base-stacking effect-mediated ultrasensitive electrochemical miRNA sensor (BSee-miR) with a universal sandwich configuration. In the BSee-miR, a short DNA probe (10 nucleotides) self-assembled on a gold electrode surface could effectively capture the target miRNA synergizing with another sequence based on coaxial sandwich base-stacking, which rivals the fully complementary strength. Importantly, such a sandwich structure is flexible to incorporate signal amplification strategies (e.g., biotin-avidin) that are usually difficult to achieve in short sequence detection. Using this design, the BSee-miR achieves a broad dynamic range with a detection limit down to 7.5 fM. Furthermore, we found a high-curvature nanostructuring synergetic base-stacking effect that could improve the sensitivity of the BSee-miR by two orders of magnitude (79.3 aM). Our BSee-miR also has a single-base resolution to discriminate the highly homologous miRNAs. More importantly, this approach is universal and has been used to probe target miRNAs varying in sequences and secondary structures. Our ultrasensitive sensor could detect miRNA in cell lysates and human blood and distinguish cancer patients from normal individuals, promising a versatile tool to measure clinically relevant miRNAs for tumor diagnostics.

Analysis of factors affecting the therapeutic effect of propranolol for infantile haemangioma of the head and neck.

Infantile haemangiomas (IHs) are the most common congenital vascular tumours of infancy. Propranolol has been demonstrated to be effective for IHs; however, the factors affecting its therapeutic effect remain unknown. We enrolled 169 infants with IHs of the head and neck region treated with oral propranolol at a dose of 2.0 mg/kg/day. We evaluated the therapeutic responses 6 months after treatment and the end of treatment, which were categorized into four grades. The type and location of the lesions and the infant age at treatment initiation were analysed. The clinical response rate (III + IV) was 91.72% at 6 months after treatment and 97.63% at the end of treatment. The average treatment duration was 9.99 (2-24) months. The group aged 4-6 months exhibited a greater therapeutic response rate (98.48%). The treatment duration was shorter (9.52 months) for mixed-type IHs. Better therapeutic responses were observed for IHs located around the parotid, periorbital, cheek, and neck regions and for multiple IH lesions. Our study indicated that propranolol is effective for IHs affecting the head and neck. The age at treatment initiation and the location of the lesions had a significant effect on the therapeutic response, whereas the lesion type might affect the treatment duration.

[Detecting Down syndrome with a novel dual-color competitive quantitative fluorescent polymerase chain reaction method].

OBJECTIVE: To develop a rapid method for the detection of Down syndrome (DS) using dual-color competitive quantitative fluorescent polymerase chain reaction (DCC-QF-PCR), and to assess its feasibility for the prenatal diagnosis of Down syndrome. METHODS: DNA was extracted from peripheral blood of 30 DS patients and 60 normal men, common primers for DSCR and USC2 genes and respective TaqMan probes were designed and synthesized. The results of DCC-QF-PCR were compared with those of QF-PCR which measured the ratio between DSCR and GAPDH. Forty-six amniotic fluid samples were assayed with DCC-QF-PCR. The results were compared with that of karyotyping. Monoclone fragments for DSCR and USC2 genes were obtained from direct cloning of PCR products. DCC-QF-PCR was carried out using different DNA ratios of DSCR and USC2 as the template. The dosage ratio between DSCR and USC2 was calculated. RESULTS: The gene dosage ratio of the DS patients was 1.41-1.74, which was significantly higher than that of normal men (0.93-1.15). The dosage ratio range of DSCR and GAPDH by QF-PCR was comparatively greater than that of DSCR and USC2. Three samples were diagnosed as DS, which was in good agreement with that of karyotyping analysis. There was no significant difference between the gene dosage ratio from DCC-QF-PCR and that of predetermined (P>0.05). CONCLUSION: DCC-QF-PCR is an accurate, rapid, and low cost method, which only requires tiny amount of sample and therefore has broad application in the genetic and prenatal diagnosis.

The mitochondria mediate the induction of NOX1 gene expression by aldosterone in an ATF-1-dependent manner.

High aldosterone (Ald) levels can induce hypertrophy of vascular smooth muscle cells (VSMCs), which carries high risks of heart failure. A previous study showed that Ald induces hypertrophy of VSMCs by up-regulating NOX1, a catalytic subunit of NADPH oxidase that produces superoxides. However, the precise mechanism remains unknown. Diphenylene iodonium (DPI) is known as an inhibitor of complex I in the mitochondrial respiratory chain, and it was also found to almost completely suppress the induction of NOX1 mRNA and the phosphorylation of activating transcription factor (ATF-1) by PGF2α or PDGF in a rat VSMC cell line. In this study, we found that the Ald-induced phosphorylation of ATF-1 and NOX1 expression was significantly suppressed by DPI. Silencing of ATF-1 gene expression attenuated the induction of NOX1 mRNA expression, and over-expression of ATF-1 restored Ald-induced NOX1 expression. On the basis of this data, we show that the mitochondria mediate aldosterone-induced NOX1 gene expression in an ATF-1-dependent manner.

[A novel deletion mutation in AR gene causes complete androgen insensitivity syndrome in a Chinese family].

OBJECTIVE: To identify the mutation of the androgen receptor (AR) gene in a complete androgen insensitivity family. METHODS: DNA was extracted from peripheral blood samples from family members in the family. PCR and DNA sequencing were then employed to detect the mutation of AR gene. RESULTS: A single nucleotide deletion of nucleotide A in exon 4 of the AR gene (1910delA) was detected in all the three patients in this family, which lead to Asn637Ile and Lys638stop. This mutation was also found in the mother (heterozygote) but was not observed in the normal controls. CONCLUSION: The 1910delA mutation of the AR gene is a novel mutation that leads to complete androgen insensitivity syndrome.