Application Value of Target Management Mode Based on Chronic Illness Trajectory Framework in Elderly Patients with Diabetes Mellitus and Cardiovascular Diseases.

Background: Diabetes and cardiovascular diseases represent significant global health challenges, leading to organ dysfunction and increased mortality rates. Managing these conditions is complex, especially in the elderly population. The study addresses this pressing issue by exploring the application of the Chronic Illness Trajectory Framework (CITF), aiming to improve self-care and quality of life in elderly patients with diabetes and cardiovascular diseases. Methods: A total of 127 patients with diabetes mellitus and cardiovascular diseases admitted to the hospital were enrolled between January 2020 and January 2022. According to the implementation of CITF management mode, they were divided into a control group (62 cases, non-implementation) and an observation group (65 cases, implementation). The control group was given routine intervention, while the observation group was given CITF-based target management mode for 3 months. The changes in blood glucose, blood lipid, negative emotions, self-efficacy, self-management, compliance, and quality of life before and after intervention in both groups were observed. This study was approved by the Ethics Committee of Zhujiang Hospital. Results: After intervention, levels of fasting plasma glucose (FPG), 2h plasma glucose (2hPG), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), scores of self-rating depression scale (SDS), self-rating anxiety scale (SAS) and Diabetes Specific Quality of Life Scale (DSQL) were decreased (P < .05), while scores of General Self-Efficacy Scale (GSES) and Scale of the Diabetes Self-Care Activities Chinese version (SDSCA), and compliance rate were increased in both groups (P < .05). The levels of FPG, 2hPG, HbA1c, TC, TG, and LDL-C, scores of SDS, SAS, and DSQL in the observation group were lower than those in the control group (P < .001), and scores of GSES and SDSCA, and compliance rate were higher than those in the control group (P < .001). These results highlight the positive role of comprehensive intervention in improving the physical and mental health of patients with diabetes and provide strong support for the application of comprehensive intervention strategies in diabetes management. Conclusion: CITF-based target management mode can alleviate negative emotions in patients with diabetes mellitus and cardiovascular diseases, improve self-management, self-efficacy, and compliance, effectively control blood glucose and lipids, and improve quality of life. The study conclusions highlight the importance of CITF management models in improving the management of patients with diabetes and cardiovascular disease. This comprehensive intervention helps reduce negative emotions, improve self-management and compliance, effectively control blood sugar and blood lipids, and improve quality of life. These results have important clinical implications and provide strong support for better care of patients with chronic diseases.

[Very-long chain acyl-coA dehydrogenase deficiency: report of a Chinese pedigree and a literature review].

OBJECTIVE: To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD). METHODS: A Chinese pedigree affected with VLCADD admitted at the First People's Hospital of Yunnan Province in February 2019 was selected as the study subject. The characteristics of disease onset, diagnosis and treatment and prognosis were retrospectively analyzed. Relevant literature was also systematically searched and reviewed. RESULTS: The proband, a 1-year-old boy, had the clinical manifestations of frequently vomiting, hypoglycemia, abnormal liver function and myocardial enzymes. Tandem mass spectrometry screening showed significantly elevated C14, C14:1, C16:1, C16:2, C18 and C14/C8. Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene, namely c.664G>A (p.G222R) and c.1345G>A (p.E449K), which were respectively derived from his father and mother. The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later. Literature review has identified 60 Chinese children with VLCADD. The clinical classifications were mainly cardiomyopathy type and liver disease type, which accounted for 73.3% (43/60). The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD. Children with one or two loss-of-function (LOF) mutations showed more severe clinical manifestation and a higher mortality. Cardiomyopathy type had the poorest prognosis, with a mortality rate of 76.9% (20/26). C14:1 may be used as an indicator for the diagnosis of VLCADD, but cannot be used for clinical subtyping and prognosis evaluation. The c.1349G>A (p.R450H) variant had the highest frequency among the Chinese patients, accounting for 10.8% (13/120). CONCLUSION: The clinical classifications of VLCADD are strongly correlated with the prognosis, and LOF mutations are more common in those with severe clinical manifestations. c.1349G>A (p.R450H) may be the most common variant among the Chinese patients, and early screening and diagnosis can greatly improve the prognosis of patients.

A typical presentation of moxifloxacin-induced DRESS syndrome with pulmonary involvement: a case report and review of the literature.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a kind of hypersensitivity drug reaction involving the skin and multiple internal organ systems. Moxifloxacin has rarely been reported to be a drug that is associated with DRESS syndrome. Lungs are less frequently involved in DRESS syndrome, but their involvements may herald more serious clinical processes. We present a rare typical case of moxifloxacin-induced DRESS syndrome with lungs involved. Valuable clinical data such as changes in the pulmonary imaging and pulmonary function tests was recorded. This case is important for the differential diagnosis of DRESS syndrome with lungs involved by providing clinical manifestations, CT imaging, pulmonary function tests, and biopsy pathological characteristics. The changes in pulmonary imaging and pulmonary function tests may help us understand the mechanism of DRESS syndrome further. CASE PRESENTATION: We report a case of a 47-year-old woman who was treated with oral moxifloxacin for community-acquired pneumonia. The patient subsequently developed a cough, fever, liver injury, skin rash, hematologic abnormalities, and shortness of breath (SOB) followed by pharyngeal herpes and peripheral neuritis. These symptoms, clinical lab index, and CT scan of the lungs improved after the withdrawal of moxifloxacin. The probability of moxifloxacin-induced DRESS syndrome was rated as "Definite", with 7 scores graded by RegiSCAR. A literature search was also performed with "fluoroquinolones," "moxifloxacin," "ciprofloxacin," "levofloxacin," "delafloxacin," and "DRESS" or "drug-induced hypersensitivity syndrome (DIHS)" as the keywords that were put into PubMed. The overall pulmonary involvement was approximately 9.1% (1/11). It is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. We summarized detailed clinical data, including pulmonary imaging and pulmonary function changes. CONCLUSION: This is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. Prompt recognition and correct diagnosis can promote appropriate treatment and accelerate recovery. This case is important for us as a reference in the differential diagnosis of DRESS syndrome and helps us further understand the mechanism of DRESS syndrome.

Gene mutations in children with permanent congenital hypothyroidism in Yunnan, China.

OBJECTIVE: To investigate molecular and clinical characteristics of children with permanent congenital hypothyroidism (CH) in Yunnan, China. METHODS: The clinical data of 40 children with CH diagnosed and treated in the First People's Hospital of Yunnan Province during January 2016 and January 2019 were retrospectively analyzed. All children were followed up to 3 years old, and Gesell intelligent score was evaluated at age of 1, 2 and 3 years, respectively. Developmental status and prognosis were evaluated. Next-generation sequencing (NGS) was used to screen all exons and exon-intron boundary sequences of the 27 known CH associated genes, and the relationship between genotypes and clinical phenotypes was analyzed. RESULTS: Among the 40 children, the thyroid related pathogenic gene mutations were detected in 23 cases with a rate of 57.5%, and a total of 32 mutations of 8 genes were detected. Mutations in DUOX2, TPO and TSHR genes were the most common ones with mutation frequencies of 65.9%(29/44), 11.4%(5/44) and 9.1%(4/44), respectively. DUOX2 gene mutations were detected in 17 children with CH, and a total of 17 mutation types were detected. p.K530* was the most common mutation in DUOX2 gene, accounting for 20.7%(6/29). There was no significant difference in physical development and intelligence assessment between children with DUOX2 heterozygous mutation and compound heterozygous mutations. None of patients could terminate medication at 3 years of the follow-up and all of them were provisionally assessed as permanent CH. The physical and mental development assessment of children with other gene mutations were also in the normal range. CONCLUSION: The detection rate of DUOX2, TPO and TSHR pathogenic mutations are high among children with permanent CH in Yunnan area, and no correlation is observed between gene mutation types and prognosis in children with CH.

Circular RNA circVAPA contributes to non-small-cell lung cancer progression via miR-342-3p-dependent regulation of ZEB2.

BACKGROUND: Accumulating evidence demonstrated that circular RNAs (circRNAs) play pivotal regulatory roles in the pathology of cancers. Disclosing the roles and molecular mechanisms of circRNAs in tumorigenesis and development is essential to identify novel diagnostic and therapeutic targets. In this study, we explored the role of circVAPA in non-small-cell lung cancer (NSCLC) progression and its associated mechanism. METHODS: The expression level of RNA was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was assessed by MTT assay and colony-forming assay. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were assessed by transwell assays. Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays were used to test the intermolecular interactions. The role of circVAPA was assessed in vivo. And xenograft tumor tissues were analyzed by immunohistochemistry (IHC) staining. RESULTS: CircVAPA expression was upregulated in NSCLC tissues and cell lines, and a high level of circVAPA was associated with a poor prognosis of NSCLC patients. CircVAPA silencing suppressed the proliferation, migration, and invasion and induced the apoptosis of NSCLC cells. CircVAPA served as a molecular sponge for microRNA-342-3p (miR-342-3p). miR-342-3p interference largely reversed circVAPA knockdown-mediated anti-tumor effects in NSCLC cells. Zinc finger E-box-binding homeobox 2 (ZEB2) was a target of miR-342-3p, and miR-342-3p overexpression suppressed the malignant behaviors of NSCLC cells largely by downregulating ZEB2. CircVAPA silence repressed xenograft tumor growth in vivo, and IHC assay confirmed that circVAPA silence restrained the proliferation and metastasis but induced the apoptosis of NSCLC cells in vivo. CONCLUSION: CircVAPA contributes to the progression of NSCLC by binding to miR-342-3p to upregulate ZEB2. CircVAPA/miR-342-3p/ZEB2 axis might be a novel potential target for NSCLC treatment.

Follow-up study of preterm infants with thyroid dysfunction after medication. / ç”²çŠ¶è ºåŠŸèƒ½å¼‚å¸¸æ—©äº§å„¿å¹²é¢„æ²»ç–—çš„éšè®¿ç ”ç©¶.

OBJECTIVES: To study the effect of levothyroxine sodium tablets on the growth and development and thyroid function in preterm infants with thyroid dysfunction. METHODS: A retrospective analysis was performed for 82 preterm infants who were born in the Department of Obstetrics of the First People's Hospital of Yunnan Province, from January 1, 2013 to December 31, 2017, and these infants were hospitalized after birth in the Department of Neonatology of the hospital. They were regularly followed up to observe growth and development and thyroid function at the outpatient service of the Department of Neonatology. According to thyroid function test results, they were divided into an abnormal thyroid function group (observation group; n=31) and a normal thyroid function group (control group; n=51). The infants in the observation group were given oral administration of levothyroxine sodium tablets, while those in the control group were not given any treatment. The two groups were compared in terms of the physical and intelligence development and thyroid function of preterm infants with various gestational ages (28-<32 weeks, 32-<34 weeks, and 34-<37 weeks) after regular follow-up to the corrected age of 12 months. RESULTS: There were no significant differences in physical development indices (body length, body weight, and head circumference) between the observation and control groups at various gestational ages after follow-up to the corrected age of 12 months (P>0.05). There were no significant differences between the two groups in the scores of each functional area of the Gesell Developmental Scale among the preterm infants with a gestational age of 28-<32 weeks and 32-<34 weeks after follow-up to the corrected age of 12 months (P>0.05). For the preterm infants with a gestational age of 34-<37 weeks, compared with the control group, the observation group had a significantly lower score of gross motor ability at the age of 3 and 12 months, significantly lower scores of fine motor ability, language ability, and adaptation ability at the age of 12 months (P<0.05), and a significantly lower score of personal-social ability at the age of 3 months (P<0.05). However, the score of personal-social ability in the observation group was not significantly different from the control group at the age of 12 months (P>0.05). After 2-4 weeks of treatment with levothyroxine sodium tablets, the thyroid function of the 31 preterm infants with thyroid dysfunction returned to normal. Among the 31 infants, 21 (68%) achieved complete drug withdrawal, with normal results of neonatal screening (100%); 10 infants (32%) failed to achieve drug withdrawal, and only 2 (20%) out of the 10 infants had normal neonatal screening results (P<0.05). CONCLUSIONS: Early diagnosis and reasonable treatment can reduce the impact on growth and development in preterm infants with thyroid dysfunction. Most preterm infants tend to have transient thyroid dysfunction, while those with positive results of neonatal screening are more likely to develop permanent thyroid dysfunction.

Baicalin attenuates inflammatory pain associated depressive symptoms via Akt-mediated adult hippocampal neurogenesis.

Depression is one of main symptoms accompanying thermal hyperalgesia and mechanical allodynia induced by inflammatory pain. On physiological level, depressive symptoms could be attenuated by sufficient level of hippocampal neural plasticity. Adult hippocampal neurogenesis (AHN) plays critical roles in clearing panic memory, increasing psychiatric adaptability and preventing depressive emotion. Thus, targeting AHN is the applicable strategy to improve neural functions impaired and attenuate inflammatory pain. Previous reports indicate natural compound baicalin (BA) is one of the effective agents to promote AHN. In present study, we tested the effects of BA in mouse model of inflammatory pain as well as its biological underpinning. Behavioral tests indicate that BA treatment attenuated thermal hyperalgesia, mechanical allodynia and depressive symptoms. Meanwhile, treatment of BA promoted growth and differentiation of neural stem cells in hippocampus. AHN blocker temozolomide (TMZ) resulted in significant suppressed effects of BA to promote AHN, suggesting the critical role of AHN in regulating behavioral effects of BA to inflammatory pain. Akt plays the critical roles in the effects of BA to attenuate inflammatory pain induced symptoms. Prohibiting of Akt with GSK960693 dramatically prevented the effects of BA in attenuating inflammatory pain induced behavioral symptoms. Taken together, BA is the potential pain killer to alleviating inflammatory pain via Akt-mediated adult hippocampal neurogenesis.

[Result of carrier screening for spinal muscular atrophy among 3049 reproductive-age individuals from Yunnan region].

OBJECTIVE: To perform carrier screening for spinal muscular atrophy (SMA) among 3049 reproductive-age individuals from Yunnan region and determine the copy number of survival motor neuron (SMN) gene and carrier frequencies. METHODS: Multiplex ligation-dependent probe amplification (MLPA) was used to determine the copy number of exon 7 of SMN1 and SMN2 genes and identify those with a single copy of SMN1 gene. Prenatal diagnosis was performed for couples whom were both found to be SMA carriers. RESULTS: In total 62 SMA carriers were identified among the 3049 subjects, which yielded a carrier frequency of 1 in 49 (2.03%). No statistical difference was found in the carrier frequency between males and females (1.91% vs. 2.30%, P>0.05). Respectively, 1.3% (41/3049) and 0.69% (21/3049) of the carriers were caused by heterozygous deletion and conversion of the SMN1 gene. The average copy number for SMN1 alleles was 1.99. Two couples were found to be both as SMA carriers, for whom the birth of an affected fetus was avoided by prenatal diagnosis. CONCLUSION: No difference was found in the carrier frequency of SMA-related mutations between the two genders in Yunnan region, which was in keeping to an autosomal recessive inheritance pattern. Determination of the carrier frequency for SMA and SMN gene variants may provide a basis for genetic counseling and prenatal diagnosis for the disease.

[Association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy].

OBJECTIVE: To study the association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy (SMA). METHODS: A total of 45 children with SMA were enrolled. Multiplex ligation-dependent probe amplification was used to measure the gene copy numbers of SMN1 and SMN2. The association of copy number of SMN1 and SMN2 with clinical phenotypes was analyzed. RESULTS: Of the 45 children with SMA, 42 (93%) had a homozygous deletion of SMN1 exons 7 and 8, and 3 (7%) had a deletion of SMN1 exon 7 alone. No association was found between SMA clinical types and the deletion types of SMN1 exons 7 and 8 (P>0.05). There was a significant difference in the distribution of SMN2 gene copy numbers between the children with SMA and the healthy children (P<0.05). The children with SMA usually had two or three copies of SMN2 gene, while the healthy children usually had one or two copies of SMN2 gene. There was a significant difference in the distribution of SMN2 copy numbers among the children with different SMA clinical types (P<0.05). The children with two copies of SMN2 gene had a significantly lower age of onset than those with three or four copies. Most of the children with type I SMA had two or three copies of SMN2 gene. Most of the children with type II SMA had three copies of SMN2 gene. Most of the children with type III SMA had three or four copies of SMN2 gene. Children with a higher copy number of SMN2 gene tended to have an older age of onset and better motor function and clinical outcome, and there was a significant association between SMN2 gene copy number and clinical outcome (P<0.05). CONCLUSIONS: The SMN2 gene can reduce the severity of SMA via the dosage compensation effect. SMN2 copy number is associated with the phenotype of SMA, and therefore, it can be used to predict disease severity.

[Genetic analysis and prenatal diagnosis for a pregnant woman with an unbalanced t(1;2), t(6;7) translocation and intellectual disability].

OBJECTIVE: To provide genetic analysis for a pregnant woman with chromosomal translocations and intellectual disability, and to provide prenatal diagnosis for her fetus. METHODS: Routine G-banding was performed to analyze the karyotypes of the woman and her fetus. Copy number variants were determined with array comparative genomic hybridization (array-CGH). RESULTS: The pregnant woman has carried an apparently balanced translocation involving chromosomes 1, 2, 6 and 7, with a karyotype of 46, XX, t(1;2) (p22;p23), t(6;7) (q21;p15). The karyotype of her fetus was ascertained as 46, XY, t(6;7) (q21;p15) mat. Array-CGH has detected a 4 Mb microdeletion at 6q22.1-q22.31 (115 311 507-119 332 956) in both individuals. As the 6q22.1-q22.31 microdeletion may be associated with the main clinical manifestations of the woman, the family decided to terminate the pregnancy. The fetus was male and appeared to have no obvious abnormality. CONCLUSION: Prenatal diagnosis for pregnant women with translocations and mental retardation is a challenging task. Combined application of cytogenetic analysis and array-CGH may facilitate the diagnosis and genetic counseling.

[Analysis of treatment efficacy for congenital hypothyroidism in some regions of Yunnan Province, China].

OBJECTIVE: To observe the effects of initial doses and treatment timing of levothyroxine (L-T4) on the clinical efficacy in children with congenital hypothyroidism (CH). METHODS: This study included 98 children who had an abnormal level of thyroid stimulating hormone (TSH) in neonatal screening in four regions of Yunnan Province and who finally had a confirmed diagnosis of CH. They received treatment with L-T4 and were divided into standard dose group (10-15 µg/kg per day) and low dose group (<10 µg/kg per day) by the therapeutic dose of L-T4. Meanwhile, these patients were also classified into two treatment groups based on the starting time of L-T4 treatment, namely under 2 months old group and more than 2 months old group. The thyroid function and physical and neural development were examined before and after treatment. RESULTS: Compared with the low dose group, the standard dose group had a significantly lower TSH level and a significantly higher free thyroxine (FT4) level at 2 weeks after treatment (P<0.05). There were no significant differences in TSH and FT4 levels at other time points after treatment between the standard and low dose groups (P>0.05). The physical and neural development were not significantly different between the two dose groups before and at all time points after treatment (P>0.05). At all time points after treatment, the levels of TSH and FT4 and physical development were not significantly different between the different starting time groups (P>0.05). However, the Gesell score was significantly higher in the under 2 months old group than in the more than 2 months old group at all time points after treatment (P<0.05). CONCLUSIONS: The standard dose group has a better treatment outcome than the low dose group, whereas the symptoms of hyperthyroidism deserve close attention. The treatment timing is vital to the neurodevelopment of children with CH. Once diagnosed, the patients should receive treatments immediately.

[Application of BoBs technique for detecting common chromosome microdeletion and microduplication syndromes].

OBJECTIVE: To establish a strategy for screening and diagnosing common microdeletion and microduplication syndromes among children with idiopathic mental retardation and development abnormalities. METHODS: Potential chromosomal variations among patients with unexplained mental retardation, cardiac anomalies, particular facial features, learning disabilities and other clinical characteristics were detected with bacterial artificial chromosome BACs-on-Beads (BoBs) technique and karyotyping. Positive results were verified with array-based comparative genomic hybridization (Array-CGH). RESULTS: Fifty eight of the 60 patients had a normal chromosome karyotype. Ten patients with microdeletion and microduplication syndromes were detected by BoBs, which included two positive cases identified through chromosome karyotyping. Two patients were respectively diagnosed as Smith-Magenis syndrome and Prader-Willi/Angelman syndrome by BoBs and the results were confirmed by Array-CGH. CONCLUSION: BoBs is capable of detecting chromosome microdeletion and microduplication with high specificity and throughput, which can compensate the shortcomings of conventional cytogenetic technology and will be widely applied for clinical diagnosis.

[Mutations of phenylalanine hydroxylase gene detected in 20 patients with phenylketonuria from Yunnan Province].

OBJECTIVE: To investigate the mutations of phenylalanine hydroxylase (PAH) gene in 20 phenylketonuria (PKU) patients from Yunnan. METHODS: The 13 exons and the splicing regions of 12 introns of the PAH gene were sequenced to detect mutations in 20 unrelated PKU patients. RESULTS: PAH gene sequencing has revealed 15 types of mutations, in which the most frequently mutation was p.R243Q (30.0%), followed by p.Y356X(10.0%), p.R111X (7.5%), IVS4+2T>A (7.5%) and p.V399V (7.5%). Exons 7, 11, 3 and introns 4, 11 were most frequently involved. Six novel mutations, including c.59A>C, c.60G>C, c.690_691insG, c.1119_1120insT, c.441+2T>A, c.842+4A>T and c.1200+1T>G were detected. CONCLUSION: PAH gene mutations identified in Yunnan are more similar to those of northern China, with R243R being the most common, though there are still certain characteristics for the type and frequency of mutations.

[Analysis of neonatal screening results for congenital hypothyroidism in parts of Yunnan Province, China].

OBJECTIVE: To summarize and analyze neonatal screening results for congenital hypothyroidism (CH) in parts of Yunnan Province, China. METHODS: A total of 236 218 newborns (121 463 males and 114 755 females) who were born in Zhaotong City, Qujing City, Lijiang City, and Diqing Tibetan Autonomous Prefecture of Yunnan Province, China, between July 2012 and April 2014 were screened for CH. The original blood smear was re-tested if the thyroid stimulating hormone (TSH) level in heel blood was ≥8 µIU/L in the initial screening. The newborns with positive TSH results were called back for further diagnosis by measuring blood TSH and free thyroxine (FT4) levels. RESULTS: Among 236 218 newborns, the pass rate of blood smears, re-acquisition rate of unqualified blood smears, and recall rate of suspected cases were 96.67%, 81.75%, and 73.02%, respectively. Sixty-six cases of CH were confirmed, among which 36 were male infants and 30 were female infants (P>0.05). The incidence rate of CH was 1/3 579, which was significantly lower than the national average rate (1/2 034; P<0.01). The gestational age of CH newborns was mostly between 37 to 42 weeks, and only 3% were born at a gestational age of >42 weeks. Most of the CH newborns had normal birth weight. The CH newborns with a body length of <50 cm accounted for 32%. CONCLUSIONS: The incidence of CH in Yunnan Province is lower than the national average. There are no specific clinical features in CH newborns. The neonatal screening in Yunnan Province needs further improvement.

In Vitro and In Vivo Supplementation with Curcumin Promotes Hippocampal Neuronal Synapses Development in Rats by Inhibiting GSK-3ß and Activating ß-catenin.

The human fetal thyroid gland is not capable of producing thyroid hormones independently until 20 weeks of gestation, and if maternal thyroid hormone synthesis is inadequate in early pregnancy, fetal brain and nerve development may be affected by maternal hypothyroidism. Curcumin, which is isolated from turmeric (Curcuma longa), has been shown to be effective in repairing neurological disorders and is effective in relieving nerve damage when consumed over a long period of time. In this experiment, we investigated the effect of curcumin supplementation on synaptic development of rat hippocampal neurons. A cell model of oxidative damage and a young rat model of hypothyroidism were constructed, and model cells and rats were treated with triiodothyronine (T3), tetraiodothyronine (T4), and curcumin, respectively. Damage of nerve cells and animal brain tissues was examined, and the effect of curcumin in alleviating the blocked neurodevelopment was investigated. Further modulation of GSK-3ß/ß-catenin was performed to investigate the mechanism of action of curcumin. Ultimately, we found that T3-, T4-, and curcumin-treated model cells and young rats had increased numbers of synapses and good neurodevelopment. At the same time, we found that curcumin inhibited the production of GSK-3ß and Axin to activate ß-catenin. The inhibition of ß-catenin weakened the therapeutic effect of curcumin, and the differences between the indicators and the model group disappeared. Both cellular and animal experiments supported that curcumin effectively alleviated the oxidative cell damage caused by thyroxine deficiency and activated the synaptogenic ability of nerve synapses by inhibiting GSK-3ß and protecting ß-catenin activity.

Quantitative assessment of inflammation and evaluation of spatial heterogeneity for non-alcoholic fatty liver disease in mice based on iron-adjustive T1.

Background: A sensitive and non-invasive method is necessary to diagnose non-alcoholic fatty liver disease (NAFLD). We explored the iron-adjustive T1 (aT1) ability to quantify the degree of liver inflammation and evaluate the spatial heterogeneity. Methods: Male C57BL/6J mice were randomly categorized as the NAFLD model (n=40), NAFLD-related liver cirrhosis model (n=20), and normal mice (n=10). T1 and T2* maps were acquired using a 3.0T scanner of magnetic resonance imaging (MRI) and aT1 maps through post-processing corrected iron's effect on T1 using T2*. Pathological changes in the left and right liver lobes were assessed using the Non-alcoholic Steatohepatitis-Clinical Research Network scoring system, though hepatic ballooning lesion were rare in models. Spearman's and partial correlation analyses were used to evaluate correlations, and the receiver operating characteristic curve was used to analyze the diagnostic performance. Results: aT1 was highly correlated with NAFLD activity score (NAS) (r=0.747, P<0.001) but not with the fibrosis stage when adjusted by NAS (r=-0.135, P=0.147). The area under the curve (AUC) of the aT1 value distinguishing groups with 0< NAS <4 and NAS ≥4 was 0.802. On analyzing the histogram features of aT1, the entropy, interquartile range, range, and variance were significantly different between the groups with 0< NAS <4 and NAS ≥4 (P<0.05). The entropy was the risk factor of NAS ≥4. Conclusions: aT1 could help evaluate the inflammatory activity in NAFLD mice unaffected by mild fibrosis, and the higher the degree of inflammation, the higher the heterogeneity of the aT1 map.

Molecular Mechanisms of Medicinal Plant Securinega suffruticosa-derived Compound Securinine against Spinal Muscular Atrophy based on Network Pharmacology and Experimental Verification.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a severe motor neuronal disorder with high morbidity and mortality. Securinine has shown the potential to treat SMA; however, its anti-SMA role remains unclear. OBJECTIVE: This study aims to reveal the anti-SMA mechanisms of securinine. METHODS: Securinine-associated targets were acquired from Herbal Ingredients' Targets (HIT), Similarity Ensemble Approach (SEA), and SuperPred. SMA-associated targets were obtained from GeneCards and Dis- GeNET. Protein-protein Interaction (PPI) network was constructed using GeneMANIA, and hug targets were screened using cytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfifiler. Molecular docking was conducted using Pymol and Auto- Dock. In vitro assays were used to verify the anti-SMA effects of securinine. RESULTS: Twenty-six intersection targets of securinine and SMA were obtained. HDAC1, HDAC2, TOP2A, PIK3R1, PRMT5, JAK2, HSP90AB1, TERT, PTGS2, and PAX8 were the core targets in PPI network. GO analysis demonstrated that the intersecting targets were implicated in the regulation of proteins, steroid hormones, histone deacetylases, and DNA transcription. KEGG analysis, pathway-pathway, and hub target-pathway networks revealed that securinine might treat SMA through TNF, JAK-STAT, Ras, and PI3K-Akt pathways. Securinine had a favorable binding affinity with HDAC1, HSP90AB, JAK2, PRMT5, PTGS2, and TERT. Securinine rescued viability suppression, mitochondria damage, and SMN loss in the SMA cell model. Furthermore, securinine increased HDAC1 and PRMT5 expression, decreased PTGS2 expression, suppressed the JAK2-STAT3 pathway, and promoted the PI3K-Akt pathway. CONCLUSION: Securinine might alleviate SMA by elevating HDAC1 and PRMT5 expression and reducing PTGS2 via JAK2-STAT3 suppression and PI3K-Akt activation.

Quantitative assessment of brown adipose tissue whitening in a high-fat-diet murine model using synthetic magnetic resonance imaging.

Purpose: This study aimed to quantitatively evaluate the whitening process of brown adipose tissue (BAT) in mice using synthetic magnetic resonance imaging (SyMRI) and analyzed the correlation between SyMRI quantitative measurements of BAT and serum lipid profiles. Methods: Fifteen C57BL/6 mice were divided into three groups and fed different diets as follows: normal chow diet for 12 weeks, NCD group; high-fat diet (HFD) for 12 weeks, HFD-12w group; and HFD for 36 weeks, HFD-36w group. Mice were scanned using 3.0 T SyMRI. T1 and T2 values of BAT and interscapular BAT (iBAT) volume were measured. After sacrifice, the body weight of mice, lipid profiles, BAT morphology, and uncoupling protein 1 (UCP1) levels were determined. Statistical analysis was performed using one-way analysis of variance or Kruskal-Wallis test followed by Bonferroni correction for pairwise comparisons. Bonferroni-adjusted significance level was set at P < 0.017 (alpha: 0.05/3 = 0.017). Results: T2 values of BAT in the HFD-12w group were significantly higher than those in the NCD group (P < 0.001), and those in the HFD-36w group were significantly higher than those in the other two groups (both P < 0.001). The iBAT volume in the HFD-36w group was significantly higher than that in the HFD-12w (P = 0.013) and NCD groups (P = 0.005). T2 values of BAT and iBAT volume were significantly correlated with serum lipid profiles and mouse body weight. Conclusions: SyMRI can noninvasively evaluate the whitening process of BAT using T2 values and iBAT volume, thereby facilitating the visualization of the whitening process.

Newborn Screening for Inborn Errors of Metabolism by Next-Generation Sequencing Combined with Tandem Mass Spectrometry.

The aim of this study was to observe the outcomes of newborn screening (NBS) in a certain population by using next-generation sequencing (NGS) as a first-tier screening test combined with tandem mass spectrometry (MS/MS). We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. The three most common IEMs were methylmalonic academia (MMA), primary carnitine deficiency (PCD) and phenylketonuria (PKU). The five genes with the most common carrier frequencies were PAH (1:42), PRODH (1:51), MMACHC (1:52), SLC25A13 (1:55) and SLC22A5 (1:63). Our study showed that NBS combined with NGS and MS/MS improves the performance of screening methods, optimizes the process, and provides accurate diagnoses.

A case report of a novel HIST1H1E mutation and a review of the bibliography to evaluate the genotype-phenotype correlations.

BACKGROUND: HIST1H1E is a member of the H1 gene family. Excess de novo likely gene-disruptive variants involving the C-terminal tail of HIST1H1E have been reported in neurodevelopmental disorders. Although clinical phenotypes in some patients have been described in single studies, few studies have reviewed the genotype and phenotype relationships using a relatively large cohort of patients with HIST1H1E variants. METHODS: Whole-exome sequencing (WES) was performed on the proband. The variant was validated using Sanger sequencing in both proband and parents. Published HIST1H1E variants in neuropsychiatric disorders were reviewed. RESULTS: Herein, we reported a new de novo frameshift mutation in HIST1H1E (NM_005321.2, c.416_419dupAGAA, p.Ala141GlufsTer56) in an individual with Rahman syndrome. To explore the genotype-phenotype correlations for HIST1H1E variants in neurodevelopmental disorders, we comprehensively curated and summarized 23 variants and the clinical features from 52 patients. Our findings revealed that likely gene-disrupting variants in HIST1H1E contribute to a wide range of neurodevelopmental phenotypes. We observed the common phenotypes including craniofacial features, ID, hypotonia, and autism/behavior problem in patients with HIST1H1E variants. While the different genotypes corresponding to different phenotypes or the same phenotype were also observed. CONCLUSION: These data provide scientific evidence for the genetic diagnosis and precision clinical management.