Objective To develop and validate a fatigue risk nomogram model in Chronic Obstructive Pulmonary Disease(COPD)patients.Methods A prospective study design was adopted,and 430 COPD patients recruited from a tertiary A hospital in Huzhou City from January to December 2022 were conveniently selected for model construction,and 129 patients were recruited from the same hospital from January to June 2023 for external validation of the model.The general information questionnaire,Pittsburgh Sleep Quality Index,2-item Generalized Anxiety Disorder Scale,2-item Patient Health Questionnaire,modified British Medical Research Council Dyspnea Index,International Physical Activity Questionnaire,and Fatigue Severity Scale were used for questionnaire survey.The risk prediction model and nomograms model were constructed using Logistic regression analysis and R 4.3.2 software,and the area under the receiver operating characteristic(ROC)curve was used to test the prediction effect of the model.Results Univariate and binary logistic regression analysis results showed that age(OR=1.095),gender(OR=2.077),dyspnea(OR=3.309),sleep quality(OR=1.979),anemia(OR=3.289),the number of acute exacerbation(OR=2.991)were independent influencing factors for fatigue in COPD patients.The internal evaluation and external validation results of the model showed that the areas under the curve are 0.912 and 0.844 respectively,and the Hosmer-Lemeshow goodness of fit test P values were 0.806 and 0.526 respectively.The average absolute errors were 0.013 and 0.019 respectively.Conclusion The COPD fatigue risk prediction model constructed in this study has good prediction effect.The visual nomogram is intuitive,convenient and easy to operate.It can provide a tool for early screening of fatigue in COPD patients.

OBJECTIVES: To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.
Adolescent ; Infant ; Child, Preschool ; Humans ; Child ; Critical Illness ; Prognosis ; Child, Hospitalized ; Chronic Disease ; Intensive Care Units, Pediatric

The pathogenesis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is highly heterogeneous and still unclear. Additional novel variants have been recently detected in the population. The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization. To address this problem, we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency. Marked deficiencies in fatty acid oxidation (FAO) and other mitochondrial defects were observed in cells carrying one of these six variants (c.541C>T, c.863T>G, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A), including reductions in mitochondrial respiratory-chain function and adenosine triphosphate (ATP) production, and increased levels of mitochondrial reactive oxygen species (ROS). Intriguingly, higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress. Moreover, the stability of the mutant homodimer was disturbed, and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics (MD) simulation. The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.

【Objective】 To investigate the expressions of ubiquitin-conjugating enzyme(UBE2) family and ubiquitin-conjugating enzyme E2T(UBE2T) gene and their relationships with the clinicopathology in lung adenocarcinoma. 【Methods】 Based on Linkedomics database, the expression levels of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA and their associations with the clinical characteristics of lung adenocarcinoma were collected and detected. Kruskal-Wallis H test was applied to compare the differences of pathologic stage, T stage and N stage, Wilcoxon rank sum test for M stage and Cox regression test for overall survival(OS). The expression profiles of UBE2T gene in lung adenocarcinoma and paracancerous tissues were obtained from the Cancer Genome Atlas(TCGA) database and then analyzed with independent samples t test. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway and the enrichment were examined by using Gene Set Enrichment Analysis(GSEA) software. 【Results】 The expressions of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA correlated with the clinicopathological features of lung adenocarcinoma. Compared with low UBE2T expression, high UBE2T expression predicted shorter OS time and advanced TNM stage. Their differences were statistically significant(P < 0.05). The UBE2T mRNA expression level was significantly upregulated in lung adenocarcinoma(P < 0.01). The gene enrichment analysis showed that the overexpression of UBE2T was closely related to 36 signal pathways(FDR < 0.05), including cell cycle(FDR = 0), spliceosome(FDR = 0), DNA repair(FDR = 0) and the glucose metabolism. The expressions of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA in UBE2 family correlated with the clinicopathological features of lung adenocarcinoma. UBE2T was further identified as a factor most closely related with pathological grade, prognosis in lung adenocarcinoma and glycolysis process of tumor cells. 【Conclusion】 UBE2 family correlates with clinicopathological features of lung adenocarcinoma. UBE2T mRNA could be a new biomarker for lung adenocarcinoma.

OBJECTIVE: To investigate the epidemiological characteristics, phenotype, genotype, and prognosis of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in the Chinese population. METHODS: A retrospective analysis was performed for the clinical data of the neonates who underwent screening with high-performance liquid chromatography-tandem mass spectrometry from January 2009 to June 2018 and were diagnosed with MCADD by gene detection. RESULTS: A total of 2 674 835 neonates underwent neonatal screening, among whom 12 were diagnosed with MCADD. Gene detection was performed for 10 neonates with MCADD and found 13 mutation types at 16 mutation sites of the ACADM gene, among which there were 7 reported mutations (p.T150Rfs*4, p.M1V, p.R206C, p.R294T, p.G310R, p.M328V, and p.G362E), 5 novel mutations (p.N194D, p.A324P, p.N366S, c.118+3A>G, and c.387+1del G), and 1 exon 11 deletion; p.T150Rfs*4 was the most common mutation (4/16). The detection rate of mutation sites in the ACADM gene was 80%. No phenotype-genotype correlation was observed. Dietary guidance and symptomatic treatment were given after confirmed diagnosis. No acute metabolic imbalance was observed within 4-82 months of follow-up. All neonates had good prognosis except one who had brain dysplasia. CONCLUSIONS MCADD is relatively rare in southern China, and p.T150Rfs*4 is a common mutation in the Chinese population. Cases with positive screening results should be evaluated by octanoylcarnitine C8 value and gene detection.
Acyl-CoA Dehydrogenase ; deficiency ; Carnitine ; China ; Follow-Up Studies ; Humans ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; Mutation ; Neonatal Screening ; Retrospective Studies

Dendrobium officinale is not only an ornamental plant, but also a valuable medicinal herb that is widely used in traditional Chinese medicine. However, distinguishing D. officinale from other Dendrobium species is usually a difficult task. In this study, we developed a rapid identification protocol for D. officinale using the loop-mediated isothermal amplification (LAMP) method. A set of primers were specifically designed to detect a modified internal transcribed spacer region of D. officinale at 65 °C within 40 min after adding SYBR Green I, which was used for the detection of D. officinale. Unlike commonly used adulterants, reaction mixtures containing D. officinale DNA changed from orange to green, and this color change was easily observed with the naked eye. Thus, this methodology can be used to accurately differentiate D. officinale from other Dendrobium species, is quick as all D. officinale samples were amplified within 40 min, and specific as samples of the adulterants were not amplified. The specificity of this LAMP-based method was confirmed by testing 17 samples of D. officinale and 32 adulterant samples from other Dendrobium species. This LAMP-based rapid identification method does not require expensive equipment or specialized techniques and can be used in field surveys for accurate and fast on-site identification.

Primary carnitine deficiency is an autosomal recessive hereditary disease caused by the mutation of SLC22 A5 gene,which leads to increased carnitine excretion in urine and low level of carnitine in blood,tissues and cells. Due to the heterogeneity and non-specificity of the clinical manifestations of PCD,it is easy to be misdiagnosed or missed and it is potentially fatal without timely treatment. This disease can be detected early through the newborn screening. Maternal carnitine deficiency and the secondary carnitine deficiency caused by other diseases should be excluded. Genetic test can give a clear diagnosis. Avoiding hunger and use of oral L-carnitine supplementation to maintain normal plasma carnitine concentrations are effective treatments.

Molecular pharmacognosy( MP) is a new interdisciplinary science,which integrates the pharmacognosy and molecular biology,and focuses on the crude drugs' classification and identification,cultivation and protection,and production of active ingredients at the molecular level. Pogostemon cablin is one of the ten major southern medicines in China,MP research on this famous herb has developed on the basis of traditional research methods,and achieved certain results. This article summarized the MP research achievements of P. cablin in recent years,the prospect of this field is also discussed to provide references for the protection,development and utilization of P. cablin resources.
China ; Lamiaceae ; Molecular Biology ; Pharmacognosy ; Pogostemon

The aim of this paper is to study the effect of astragaloside Ⅳ on renal fibrosis mice with ischemia-reperfusion injury (IRI) and discuss the mechanism. Male C57BL/6 50 mice were randomly divided into four groups, namely Sham-operated group, model group, AS-Ⅳ prevention group and AS-Ⅳ treatment group. Since the day of surgery, the mice in astragaloside Ⅳ prevention group were treated with astragaloside Ⅳ by gavage for 30 days at the dose of 30 mg·kg⁻¹·d⁻¹. At the 60th day after surgery, the mice in astragaloside Ⅳ treatment group were treated with astragaloside Ⅳ 100 by gavage for 30 days at the dose of 30 mg·kg⁻¹·d⁻¹. The mice in Sham-operated group and model group were treated with double distilled water containing 0.1% ethanol instead of astragaloside Ⅳ. Serum creatinine and blood urea nitrogen were detected by chemical methods. Histopathological changes and collagen deposition of affected kidneys were observed under optical microscope by HE and Masson staining. The expression levels of Toll like receptor pathway related molecules (TLR4,MyD88,TRAF6,TRAM,TRIF,NF-κB,TNF-α,IL-6, IFN-) in affected kidneys were observed by immunohistochemistry, Western blot methods and reverse transcription-PCR atprotein and mRNA levels in each group. The results showed that the degrees of fibrosis and histopathological damage of affected kidneys of mice in model group were the most obvious. And the expression levels of TLR4/MyD88 dependent signaling pathway-related molecules (TLR4 and MyD88, TRAF6 and NF-κB) in affected kidneys of mice in model group were the highest. At the same time, there was no difference in the expression levels of TLR4/MyD88 independent signaling pathway-related molecules（TRAM, TRIF）among sham-operated group, model group, astragaloside IV prevention group and astragaloside Ⅳ treatment group. In astragaloside Ⅳ prevention group and astragaloside Ⅳ treatment group, the injury of affected kidney was obviously reduced, and the protein expression levels of TLR4/MyD88 dependent signaling pathway-related molecules were also correspondingly reduced; at the same time, the expressions of terminal inflammatory cytokines (TNF-α,IL-6, IFN-) were suppressed. Therefore, astragaloside Ⅳ may improve renal interstitial fibrosis in mice after IRI by inhibiting the expression of TLR4/MyD88 dependent signaling pathway and the release of inflammatory cytokines (TNF-α,IL-6, IFN-), while the TLR4/MyD88 independent signaling pathway may not be involved in the process of renal fibrosis after ischemia-reperfusion injury.

Objective To explore the ultrasound features and levels of cervical lymph node metastases in primary and recurrent/persistent papillary thyroid cancer (PTC).Methods We retrospectively analyzed the clinical data of 2181 patients who underwent cervical lymph nodes dissection for PTC from January 12015 to January 12016.Totally 418 PTC patients (with 622 lymph nodes) who met the inclusion criteria entered the final analysis.Patients who had not received any prior thyroid treatment (surgery with or without radioactive iodine) were categorized as the primary group (352 patients with 527 metastatic lymph nodes),and patients who had received prior treatment (thyroidectomy with or without radioactive iodine) for PTC were categorized as recurrent/persistent group (66 patients with 95 metastatic lymph nodes).Pathological results from lymph node dissections were used as the gold standards by means of level-to-level analysis.Results The mean of the minimum axis diameter of the lymph nodes in the primary group was (6.7±3.6)mm,and that of the recurrent/persistent group was (6.6±3.1)mm (U=0.180,P=0.857).The proportion of metastasis in the central area of primary group was 40.0%,which was significantly higher than that in the recurrent/persistent group (12.6%);the proportion of metastasis in the lateral area was 60.6% in the primary group,which was significantly lower than that in the recurrent/persistent group (87.4%)(χ=26.288,P<0.001).In lateral metastatic lymph nodes,Ⅲ level was the most common place in both groups.Level Ⅴ metastatic lymph was rare in both primary group and recurrent/persistent group.Calcifications (63.1% vs. 48.2%;χ=7.207,P=0.007) and peripheral vascularity (81.1% vs. 59.4%;χ= 16.147, P<0.001) were more common in the recurrent/persistent group.The round shape,absence of an echogenic hilum,hyperechogenicity,and cystic aspects were not significantly different between these two groups (all P>0.05).Conclusions Primary metastatic lymph nodes often occur in the central area of lymph nodes,while lateral metastatic lymph nodes are more common in recurrent/persistent PTC.For metastatic lymph nodes,calcifications and peripheral vascularity are more common in recurrent/persistent PTC.