Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis.

The excessive inflammation caused by the prolonged activation of Toll-like receptor 4 (TLR4) and its downstream signaling pathways leads to sepsis. CD14-mediated endocytosis of TLR4 is the key step to control the amount of TLR4 on cell membrane and the activity of downstream pathways. The actin cytoskeleton is necessary for receptor-mediated endocytosis, but its role in TLR4 endocytosis remains elusive. Here we show that Tropomodulin 1 (Tmod1), an actin capping protein, inhibited lipopolysaccharide (LPS)-induced TLR4 endocytosis and intracellular trafficking in macrophages. Thus it resulted in increased surface TLR4 and the upregulation of myeloid differentiation factor 88 (MyD88)-dependent pathway and the downregulation of TIR domain-containing adaptor-inducing interferon-ß (TRIF)-dependent pathway, leading to the enhanced secretion of inflammatory cytokines, such as TNF-α and IL-6, and the reduced secretion of cytokines, such as IFN-ß. Macrophages deficient with Tmod1 relieved the inflammatory response in LPS-induced acute lung injury mouse model. Mechanistically, Tmod1 negatively regulated LPS-induced TLR4 endocytosis and inflammatory response through modulating the activity of CD14/Syk/PLCγ2/IP3/Ca2+ signaling pathway, the reorganization of actin cytoskeleton, and the membrane tension. Therefore, Tmod1 is a key regulator of inflammatory response and immune functions in macrophages and may be a potential target for the treatment of excessive inflammation and sepsis.

The efficacy and safety of inhaled antibiotics for pneumonia: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of inhaled antibiotics for adults with pneumonia by meta-analysis. METHODS: Literature retrieval was completed through five databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) by the deadline of May 31, 2024. The process of study selection and data extraction were performed independently by two reviewers. The quality of observational studies and randomized controlled trial (RCT) studies were evaluated by Newcastle Ottawa scale and Jadad scale, respectively. The primary outcomes included mortality, clinical cure, and microbiological cure. Secondary outcomes were recurrence and renal impairment. RESULTS: There were 30 studies were analyzed, including 12 RCT studies and 18 observational studies. Inhaled antibiotics did not significantly reduce mortality in RCT studies (odds ratio (OR) = 1.06, 95 % confidence interval (CI): 0.80-1.41). Inhaled antibiotics were associated with higher rates of clinical cure (OR = 1.47 95%CI: 0.82-2.66 in RCT studies and OR = 2.09, 95%CI: 1.36-3.21 in observational studies) and microbiological cure (OR = 7.00 in RCT studies and OR = 2.20 in observational studies). Subgroup analysis showed patients received inhaled antibiotics combined with intravenous administration and inhaled amikacin had better improvements of mortality, clinical cure and microbiological cure. Inhaled antibiotics were not associated with recurrence. The pooled OR of renal impairment were 0.65 (95%CI: 0.27-1.13; I-squared = 43.5 %, P = 0.124) and 0.63(95%CI: 0.26-1.11; I-squared = 69.0 %, P = 0.110) in RCT studies and observational studies, respectively. CONCLUSIONS: Inhaled antibiotics decreased risk of renal impairment and achieved significant improvements of clinical and microbiological cure in patients with pneumoniae.

HPPO-Derived Meroterpenoids from the Marine-Derived Fungus Penicillium sp. SCSIO 41691.

Seven new 4-hydroxy-6-phenyl-2H-pyran-2-one (HPPO) derived meroterpenoids, 1-methyl-12a,12b-epoxyarisugacin M (1), 1-methyl-4a,12b-epoxyarisugacin M (2), 2,3-dihydroxy-3,4a-epoxy-12a-dehydroxyisoterreulactone A (3), 2-hydroxy-12a-dehydroxyisoterreulactone A (4), 3'-demethoxyterritrems B' (5), 4a-hydroxyarisugacin P (6), and 1-epi-arisugacin H (7), together with two known analogues (8 and 9), were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41691. Their structures were elucidated by spectroscopic methods, and the absolute configurations of compounds 1 and 3 were determined by single-crystal X-ray diffraction. Among them, 1 and 2 had a unique methyl migration in the basic meroterpenoid skeleton with a 12a,12b-epoxy or 4a,12b-epoxy group, and 3 was a highly oxygenated HPPO-derived meroterpenoid featuring a rare 6/5/6/6/6/6 hexacyclic system with a 3,4a-epoxy group. Biologically, 5 exhibited inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC50 value of 21 µM, more potent than the positive control indomethacin.

Genomic and immunocyte characterisation of bloodstream infection caused by Klebsiella pneumoniae.

OBJECTIVES: The aim of this study was to evaluate the characteristics of immunocyte associated with bloodstream infection (BSI) caused by Klebsiella pneumoniae (Kpn). METHODS: Patients with BSI-Kpn were included from 2015 to 2022 in our hospital. Immunocyte subpopulations of enrolled BSI-Kpn patients were tested on the same day of blood culture using multicolor flow cytometry analysis. Antibiotic susceptibility test was determined by agar dilution or broth dilution method. All included isolates were subjected to whole genome sequencing and comparative genomics analysis. Clinical and genetic data were integrated to investigate the risk factors associated with clinical outcome. RESULTS: There were 173 patients with non-duplicate BSI-Kpn, including 81 carbapenem-resistant Kpn (CRKP), 30 extended-spectrum ß-lactamases producing Kpn (ESBL-Kpn), 62 none CRKP or ESBL-Kpn (S-Kpn). Among 68 ST11-CRKP isolates, ST11-O2v1:KL64 was the most common serotypes cluster (77.9%, 53/68), followed by ST11-OL101: KL47 (13.2%, 9/68). Compared with CSKP group, subpopulations of immunocyte in patients with CRKP were significantly lower (P < 0.01). In patients with ST11-O2v1:KL64 BSI-Kpn, the level of cytotoxic T lymphocytes (CD3 + CD8 +) is the highest, while the B lymphocytes (CD3-CD19 +) was the least. In addition, the level of immunocyte in patients with Kpn co-harbored clpV-ybtQ-qacE were lower than that in patients with Kpn harbored one of clpV, ybtQ or qacE and without these three genes. Furthermore, co-existence of clpV-ybtQ-qacE was independently associated with a higher risk for 30-day mortality. CONCLUSIONS: The results demonstrate that patients with BSI-CRKP, especially for ST11-O2v1:KL64, exhibit lower leukomonocyte counts. In addition, BSI-Kpn co-harbored clpV-ybtQ-qacE is correlated to higher 30-day mortality.

Dynamic cytokine profiles of bloodstream infection caused by Klebsiella pneumoniae in China.

OBJECTIVES: The aim of this work was to assess dynamic cytokine profiles associated with bloodstream infection (BSI) caused by Klebsiella pneumoniae (Kpn) and investigate the clinical features associated with mortality. METHODS: A total of 114 patients with positive BSI-Kpn and 12 sepsis individuals without blood positive bacteria culture were followed up. Cytokine profiles were analyzed by multiplex immunoassay on the first, third, seventh and fourteenth day after diagnosis. The test cytokines included arginase, interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-4, IL-6, IL-10, IL-12 (p70), and IL-23. The minimum inhibitory concentration (MIC) of 24 antibiotics were tested for BSI-Kpn. Risk factors associated with the 30-day mortality and 120-day mortality were evaluated using logistic analyses and nomogram. RESULTS: There were 55 out of 114 patients with BSI-Kpn were included. All isolates showed high susceptibility rate to novel avibactam combinations. The level of arginase was the highest in carbapenem-resistant Kpn (CRKP) patients. The AUCs of arginase, TNF-α and IL-4 reached 0.726, 0.495, and 0.549, respectively, whereas the AUC for the combination of these three cytokines was 0.805. Notably, 120-day mortality in patients with CRKP was higher than carbapenem-sensitive K. pneumoniae (CSKP). Furthermore, the long-term and high levels of IL-6 and IL-10 were associated with death. CONCLUSIONS: High expression of arginase is correlated with CRKP. In addition, BSI-CRKP could result in indolent clinic course but poor long-term prognosis. Continuous increase of IL-6 and IL-10 were associated with mortality.

Zimberelimab combined with systemic therapy extended tumor control in post-radiotherapy cervical cancer with brain metastases: A case report.

Out of the total cases of cervical cancer, brain metastases (BMs) are relatively rare, with an estimated incidence rate of 0.63% (range: 0.1%-2.2%). Additionally, BMs prognosis remains poor, and the average patient survival time following a BM diagnosis is 3 to 5 months. Few studies have addressed the effect of programmed cell death-1 inhibitors against BMs in cervical cancer, although they are an established option for recurrent/metastatic disease. Hence, we report a case involving a 54-year-old post-surgery patient with cervical cancer with a body mass index of 19.5 kg/m2 and Eastern Collaborative Oncology Group (ECOG) performance status of 3; the disease recurred with BMs 1 year later. Intensity-modulated radiation therapy concurrent with temozolomide and bevacizumab was initiated, following which zimberelimab immunotherapy combined with anlotinib was administered to extend tumor control. The patient had a progression-free survival duration of 10 months, the tumor response was assessed as a partial response based on the evaluation criteria for solid tumors (RECIST1.1), and the ECOG status improved to 1 after therapy. These findings suggest that immunotherapy-based combination therapy following radiotherapy may be a good choice for patients with cervical cancer and BMs.

Costunolide attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that can further evolve towards liver fibrosis and hepatocellular carcinoma in the end stage. Costunolide (Cos) is a natural sesquiterpene lactone that exhibits both anti-inflammatory and antioxidant properties. However, the therapeutic effect of Cos on NAFLD is not clear. In this study, we explored the potential protective effect and mechanism of Cos on NAFLD. C57BL/6 mice were fed with high-fat diet (HFD) to induce NAFLD. Cos was administered by gavage to observe the effect of Cos on NAFLD. We demonstrated that oral administration of Cos reduced HFD-induced hepatic fibrosis and the release of inflammatory cytokines, limiting the generation of reactive oxygen species. In vitro experiments revealed that pretreatment with Cos significantly decreased PA-induced production of inflammatory cytokines and fibrosis in AML-12 cells. Mechanism study showed that the effect of Cos was correlated to the induction of Nrf-2 and inhibition of NF-κB pathways. Collectively, these findings indicated that Cos exerts hepatoprotective effect against NAFLD through blocking inflammation and oxidative stress. Our study suggested that Cos might be an effective pharmacotherapy for the treatment of NAFLD.

Lecanicilliums A-F, Thiodiketopiperazine-Class Alkaloids from a Mangrove Sediment-Derived Fungus Lecanicillium kalimantanense.

Six new thiodiketopiperazine-class alkaloids lecanicilliums A-F were isolated from the mangrove sediment-derived fungus Lecanicillium kalimantanense SCSIO41702, together with thirteen known analogues. Their structures were determined by spectroscopic analysis. The absolute configurations were determined by quantum chemical calculations. Electronic circular dichroism (ECD) spectra and the structure of Lecanicillium C were further confirmed by a single-crystal X-ray diffraction analysis. Lecanicillium A contained an unprecedented 6/5/6/5/7/6 cyclic system with a spirocyclic center at C-2'. Biologically, lecanicillium E, emethacin B, and versicolor A displayed significant cytotoxicity against human lung adenocarcinoma cell line H1975, with IC50 values of 7.2~16.9 µM, and lecanicillium E also showed antibacterial activity against four pathogens with MIC values of 10~40 µg/mL. Their structure-activity relationship is also discussed.

Enhancing Prognostic Assessment for Influenza-Associated Pneumonia: An Examination of Contributing Risk Factors.

Objective: This study aims to analyze the prognostic risk factors influencing patient outcomes in cases of influenza-associated pneumonia. Methods: We comprehensively analysed clinical data from patients admitted to the First Affiliated Hospital of Wenzhou Medical University between December 2017 and April 2019. Patients with confirmed influenza-associated pneumonia, determined through nucleic acid detection in throat swabs or sputum samples, were included in the study. The collected data were meticulously analyzed to identify significant prognostic risk factors. Results: A total of 151 patients diagnosed with influenza-associated pneumonia were included in the final analysis, yielding a fatality rate of 19.87% (30/151). The application of multivariate regression analysis revealed that several independent risk factors significantly affected the prognosis of patients afflicted with influenza-associated pneumonia. These included lymphocyte count (L), oxygenation index (O), albumin (A), and urinary (U) levels. Receiver operating characteristic (ROC) curve analysis further elucidated the prognostic value of these factors. Specifically, the Composite Index LOAU (Lymphocyte, Oxygenation index, Albumin, Urinary) demonstrated a robust area under the curve (AUC) of 0.909 (95% CI: 0.851-0.950), surpassing the performance of established scoring systems, such as the pneumonia severity index (PSI) (AUC = 0.746), Apache II (AUC = 0.732), and CURB-65 (AUC = 0.662). These differences were statistically significant (P < .05). Conclusions: The prognosis of influenza-associated pneumonia can be effectively predicted by assessing peripheral blood parameters, including lymphocyte count, albumin level, urinary markers, and the oxygenation index upon admission. Notably, the Composite Index LOAU, as a comprehensive amalgamation of these factors, holds promising potential to enhance prognostic precision and management outcomes in cases of influenza-associated pneumonia.

Pyrrospirones K-Q, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Penicillium sp. SCSIO 41512.

Seven new decahydrofluorene-class alkaloids, pyrrospirones K-Q (1-7), together with six known analogues (8-13) were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41512. Their structures were determined by extensive spectroscopic analysis, and their absolute configurations were established by single-crystal X-ray diffraction analysis and quantum chemical calculations of electronic circular dichroism spectra. Compounds 1 and 3 possess a novel decahydrofluorene-class alkaloid skeleton with a 6/5/6/8/5/6/13 and a 6/5/6/5/6/13 polycyclic system, respectively. Biologically, 13 displayed significant inhibitory activity against protein tyrosine phosphatases CD45, TCPTP, SHP1, and PTP1B with IC50 values of 8.1-17.8 µM, and 1, 2, 5, 8-10, 12, and 13 showed antibacterial activity against six pathogens. Their structure-activity relationship is also discussed.

TRIM35 functions as a novel tumor suppressor in breast cancer by inducing cell apoptosis through ubiquitination of PDK1.

Breast cancer is the most common cancer in women. Novel mechanisms and targets are urgently needed to understand and treat this disease due to the complexity of breast cancer. In this study, we evaluated the expression level of tripartite motif-containing (TRIM) 35 in various breast cancer cell lines by qPCR and immunoblot. Cell proliferation assay and flow cytometry were performed upon overexpression and depletion of TRIM35. Xenograft tumor model was applied to validate the findings observed in vitro. The correlation between TRIM35 and outcomes of breast cancer patients was investigated by analyzing The Cancer Genome Atlas database. We observed differential expression of TRIM35 in various breast cancer cell lines. Overexpression of TRIM35 significantly inhibited cell proliferation and promoted cell apoptosis. On the contrary, depletion of TRIM35 exerted the opposite effects on cell proliferation and apoptosis. Mechanistically, TRIM35 reduced PDK1 by ubiquitination, resulting in the degradation of PDK1. Overexpression of TRIM35 significantly suppressed ZR7530 cell line-derived xenograft tumor growth by inducing apoptosis. Finally, a lower level of TRIM35 was associated with a poor prognosis in patients. In conclusion, TRIM35 functions as a tumor suppressor to suppress breast cancer proliferation by inactivating AKT signaling through the increased ubiquitination of PDK1, resulting in the promotion of apoptosis.

Isoquinoline Alkaloids as Protein Tyrosine Phosphatase Inhibitors from a Deep-Sea-Derived Fungus Aspergillus puniceus.

Puniceusines A-N (1-14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the structures of 6 and 12 were further confirmed by a single-crystal X-ray diffraction analysis. Compounds 3-5 and 8-13 unprecedentedly contained an isoquinolinyl, a polysubstituted benzyl or a pyronyl at position C-7 of isoquinoline nucleus. Compounds 3 and 4 showed selective inhibitory activity against protein tyrosine phosphatase CD45 with IC50 values of 8.4 and 5.6 µM, respectively, 4 also had a moderate cytotoxicity towards human lung adenocarcinoma cell line H1975 with an IC50 value of 11.0 µM, and 14, which contained an active center, -C=N+, exhibited antibacterial activity. An analysis of the relationship between the structures, enzyme inhibitory activity and cytotoxicity of 1-14 revealed that the substituents at C-7 of the isoquinoline nucleus could greatly affect their bioactivity.

Chemical Characterization and Immunomodulatory Activity of Fucoidan from Sargassum hemiphyllum.

Fucoidan is a sulfated algal polyanionic polysaccharide that possesses many biological activities. In this paper, a fucoidan (SHF) polysaccharide was extracted from Sargassum hemiphyllum collected in the South China Sea. The SHF, with a molecular weight of 1166.48 kDa (44.06%, w/w), consisted of glucose (32.68%, w/w), galactose (24.81%, w/w), fucose (20.75%, w/w), xylose (6.98%, w/w), mannose (2.76%, w/w), other neutral monosaccharides, and three uronic acids, including glucuronic acid (5.39%, w/w), mannuronic acid (1.76%, w/w), and guronuronic acid (1.76%, w/w). The SHF exhibited excellent immunostimulatory activity. An immunostimulating assay showed that SHF could significantly increase NO secretion in macrophage RAW 264.7 cells via upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) levels based on both gene expression and protein abundance. These results suggest that SHF isolated from Sargassum hemiphyllum has great potential to act as a health-boosting ingredient in the pharmaceutical and functional-food fields.

Identification of a new inhibitor of KRAS-PDEδ interaction targeting KRAS mutant nonsmall cell lung cancer.

Oncogenic KRAS is considered a promising target for anti-cancer therapy. However, direct pharmacological strategies targeting KRAS-driven cancers remained unavailable. The prenyl-binding protein PDEδ, a transporter of KRAS, has been identified as a potential target for pharmacological inhibitor by selectively binding to its prenyl-binding pocket, impairing oncogenic KRAS signaling pathway. Here, we discovered a novel PDEδ inhibitor (E)-N'-((3-(tert-butyl)-2-hydroxy-6,7,8,9-tetrahydrodibenzo[b,dfuran-1-yl)methylene)-2,4-dihydroxybenzohydrazide(NHTD) by using a high-throughput docking-based virtual screening approach. In vitro and in vivo studies demonstrated that NHTD suppressed proliferation, induced apoptosis and inhibited oncogenic K-RAS signaling pathways by disrupting KRAS-PDEδ interaction in nonsmall cell lung cancer (NSCLC) harboring KRAS mutations. NHTD redistributed the localization of KRAS to endomembranes by targeting the prenyl-binding pocket of PDEδ and exhibited the suppression of abnormal KRAS function. Importantly, NHTD prevented tumor growth in xenograft and KRAS mutant mouse model, which presents an effective strategy targeting KRAS-driven cancer.

Normal development of costal element ossification centers of sacral vertebrae in the fetal spine: a postmortem magnetic resonance imaging study.

PURPOSE: This postmortem magnetic resonance imaging (MRI) study of the fetal spine aimed to describe the timing of appearance, shape, volume, and relative positions of the S1-S3 costal element ossification centers (CEOCs). METHODS: We obtained sagittal 3D dual-echo steady-state with water excitation T2 images of the entire spine in 71 fetuses (gestational ages (GAs), 17-42 weeks). Computed tomography and histological examinations were performed on two fetal specimens (GAs, 21 and 30 weeks) to validate the MR images. The presence/absence of each sacral CEOC was recorded according to the GA. CEOC volume was measured. We analyzed the CEOC position relative to the vertebral column and ilium. RESULTS: The S1, S2, and S3 CEOCs first appeared at 23, 22, and 29 weeks, respectively. The S1 and S2 CEOCs could be detected in all fetuses with GAs of ≥ 30 weeks and ≥ 35 weeks, respectively, while the S3 CEOCs were variably present until term. The percentages of detection of the S1 and S2 CEOCs were significantly greater than that of the S3 CEOCs at each GA. At S1 and S2, the CEOC volume increased exponentially with GA. The relative positions of the S1 and S2 CEOCs, but not the S3 CEOCs, significantly correlated with GA (P < 0.001). CONCLUSION: We have described the timeline of appearance as well as the volume and position of the S1-S3 CEOCs in the fetal spine on postmortem MRI according to GA.

A Case Report of Primary Neonatal Hypocholinesterase Caused by Homozygous Frameshift Mutation of the utyrylcholinesterase (BCHE) Gene and Review of Literature.

BACKGROUND: Primary neonatal hypocholinesterase is rare; its genetic pattern and mutation still need to be further studied. METHODS: The patient and his parents are studied using next-generation sequencing technology. RESULTS: A boy one day after birth is admitted to the Neonatal Intensive Care Unit at our hospital after experiencing intermittent vomiting for 12 hours. The patient's serum cholinesterase level (113 - 283 U/L) is lower than normal value (4,000 - 12,600 U/L). Many factors of low serum cholinesterase are excluded. We highly suspect that it may be related to congenital factors. Molecular genetic test results show that the patient carried the BCHE gene (NM_000055.2) and has homozygous frameshift mutations at exon 2 c.401dupA (p.Asn134fs) of chromosome 3q26. It is a pathogenicity mutation. This locus mutation belongs to a novel pathogenic mutation. As a result of this mutation, the 134th amino acid Asn began to frameshift and the translation is terminated early. It can cause the Encoding of protein to truncate and lose its normal function. His parents' serum cholinesterase levels (father: 5,135 U/L; mother: 4,367 U/L) are in the normal value range, but his parents carried a heterozygous BCHE gene. CONCLUSIONS: This study suggests that gene sequence detection should be carried out early in hypocholinesterase of nknown cause in neonates. This study can not only improve understanding of the etiology and pathological mechanism of hypocholinesterase, but also it can enlarge the hypocholinesterase gene mutation spectrum.

Normal development of sacrococcygeal centrum ossification centers in the fetal spine: a postmortem magnetic resonance imaging study.

PURPOSE: To describe the temporal pattern of the appearance of the S1-Co1 centrum ossification centers (COCs) and provide reference data for the S1-S5 COCs and sacral length at various gestational ages (GAs). METHODS: Postmortem magnetic resonance imaging (MRI) was performed on 71 fetuses (GA, 17-42 weeks) using the 3D dual-echo steady-state with water excitation T2 sequence in the sagittal plane. To confirm the reliability of this sequence, the MRI data were compared with the CT and histologic data obtained from two fetuses (GAs, 21 and 30 weeks). The presence or absence of each sacrococcygeal COC was recorded. Sacral length and S1-S5 COC height, sagittal diameter, transverse diameter, cross-sectional area, and volume were measured. RESULTS: All fetuses showed S1-S3 COCs by 17 weeks, S4 COCs by 19 weeks, and S5 COCs by 28 weeks. The S4, S5, and Co-1 COCs were visualized in 70 (98.59%), 51 (71.83%), and 21 (29.58%) fetuses, respectively. Sacral length, height, sagittal, and transverse diameters increased linearly, while cross-sectional area and volume increased exponentially with advancing GA. Mean growth rates of the sagittal and transverse diameters, cross-sectional area, and volume, but not of height, significantly differed among the S1-S5 vertebrae. CONCLUSION: We have presented the timing of appearance of individual sacrococcygeal COCs and the age-specific, normative MRI reference values for sacral length and the morphometric parameters of the sacral COCs, which are of clinical importance in the diagnosis of congenital sacral abnormalities and skeletal dysplasia.

SATB2-Associated Syndrome: a Case Report of a De Novo Nonsense Mutation in SATB2 from China and Review of Literature.

BACKGROUND: To study the clinical and genetic features from a Chinese child with SATB2-associated syndrome (SAS) and review of literature. METHODS: The girl, 2 years 3 months old, is admitted to the Department of Pediatric Rehabilitation in our hospital. This patient has mental retardation, language development disorder, cleft palate II0, micrognathia, malocclusion, irritability and bilateral oblique palpebral fissure as a clinical manifestation and is treated for 3 months. RESULTS: Gesell Development Scale (GDS) evaluation displays the patient's action capacity: gross motor 13.4, DQ 41%; fine motor 14.1, DQ 44%; adaptive behavior: DA 15.2, DQ 47%; speech capacity: DA 8.8; DQ 27%; person capacity: DA 11.7, DQ, 36%. Bayley Scale evaluation displays MDI < 50 and PDI < 50. Sleep EEG showed bilateral frontal pole - frontal - central - anterior temporal area presents in sharp wave, sharp and slow wave synchronization issue. A brain MRI showed that signal T2 is strengthened in the internal capsule hind leg. Flake T2FLATR high signal can been showed in the periventricular area of the parietal lobe in bilateral hemisphere. Molecular studies showed the patient carries a de novo nonsense mutation c.1285G>A (p.R429X) in SATB2. CONCLUSIONS: SATB2 mutation is not detected in the parents of the subjects. This study is important to further study the clinical features of SATB2-associated syndrome and to enlarge the SATB2 mutation spectrum.

Predictive Value of Neurodevelopmental Outcome and Serum Tau Protein Level in Neonates with Hypoxic Ischemic Encephalopathy.

BACKGROUND: Tau protein is s specific protein expressed by neurons in the central nervous system. Elevated serum Tau protein is associated with many diseases of the central nervous system. The serum Tau protein level in neonates with hypoxic ischemic encephalopathy (HIE) is still poorly understood. METHODS: Forty-one human neonates with HIE and thirty-five healthy neonates (control group) within 24 hours after birth were studied. Tau protein in serum was detected by enzyme-linked immunosorbent assay. Neurological outcome was assessed at 9 months of age according to the Gesell developmental scale. RESULTS: Tau protein in serum was significantly higher in the HIE group than in the control group (p < 0.01), in neonates with severe HIE than neonates with moderate HIE (p < 0.01), and in infants with neurodevelopmental retardation compared with those with normal neurodevelopment (p < 0.01). The result of this study showed an obvious negative correlation between the serum Tau protein level and development quotients of neonates with HIE (rs = -0.6172, p < 0.01). Receiver operator characteristic curve analysis showed that Tau protein (cutoff value 933.04 pg/mL) was a predictor of neurodevelopmental retardation outcome (AUC value = 0.860 (95% CI: 0.736 - 0.983, p < 0.01), sensitivity 100%, specificity 70.8%). CONCLUSIONS: Serum Tau protein level within 24 hours after birth can be used as a marker for the early diagnosis of neonatal HIE and predicting neurodevelopmental outcomes.

Detection and Toxicity Evaluation of Pyrrolizidine Alkaloids in Medicinal Plants Gynura bicolor and Gynura divaricata Collected from Different Chinese Locations.

Two edible plants in Southeast Asia, Gynura bicolor and G. divaricata, are not only known to be nutritive but also useful as medicinal herbs. Previous phytochemical investigation of Gynura species showed the presence of hepatotoxic pyrrolizidine alkaloids (PAs), indicating the toxic risk of using these two plants. The present study was designed to analyze the distribution of PA components and tried to evaluate the preliminary toxicity of these two Gynura species. Eight samples of G. bicolor and G. divaricata from five different Chinese locations were collected and their specific PAs were qualitatively characterized by applying an UPLC/MS/MS spectrometry method. Using a pre-column derivatization HPLC method, the total retronecine ester-type PAs in their alkaloids extracts were quantitatively estimated as well. Finally, their genotoxicity was investigated with an effective high-throughput screening method referred to as Vitotox™ test and their potential cytotoxicity was tested on HepG2 cells. It was found that different types of PAs were widely present in Gynura species collected from south of China. Among them, no significant genotoxic effects were detected with serial concentrations through the present in vitro assay. However, the cytotoxicity assay of Gynura plants collected from Jiangsu displayed weak activity at the concentration of 100 mg/ml. It is important to note that this research validates in part the indication that the use of Gynura species requires caution.