Ceruloplasmin(Cp)is a crucial protein secreted by the liver and plays a vital role in regulating the distribution and transport of copper throughout the body,thereby maintaining copper homeostasis.Additionally,Cp functions as a significant enzyme known as ferroxidase,which is involved in iron metabolism within the body.Numerous studies have suggested a close relationship between Cp and metabolic disorders,such as diabetes and cardiovascular diseases.Recent research has also shed light on the involvement of Cp in the regulation of lipid metabolism.The various activities associated with lipid metabolism,including lipid synthesis,adipose hydrolysis,fatty acid oxidation,lipid transport,and absorption,collectively contribute to maintaining lipid homeostasis.Dysregulation of lipid metabolism can lead to metabolic disorders and cardiovascular complications.Cp regulates lipid metabolism through two main mechanisms.Firstly,Cp participates in the regulation of oxidative stress by modulating iron metabolism through its ferroxidase activity and involvement in redox reaction.Secondly,copper along with copper-dependent enzymes directly participates in the processes such as cholesterol metabolism,lipoprotein metabolism,and fatty acid synthesis.As a result,the role of Cp in maintaining the homeostasis of copper and iron allows it to regulate lipid metabolism by influencing copper or iron-dependent enzymes and related pathways.Although the correlation between Cp and lipid metabolism has been identified,an in-depth exploration of the precise mechanisms by which Cp governs lipid metabolism is warranted.This article provides an overview of the role of Cp in lipid metabolism and highlights the progress in related research,with the aim of providing new insights for the development and treatment of disorders related to lipid metabolism.

Objective: To investigate the factors affecting the development of malnutrition among the elderly patients with type 2 diabetes mellitus (T2DM), so as to provide insights into the prevention of malnutrition among the elderly patients with T2DM. Methods: Elderly T2DM patients at ages of 60 years and older admitted to Hangzhou First People's Hospital affiliated to Zhejiang University School of Medicine from June 2022 to June 2023 were recruited. Patients' demographics, number of medicines administered and comorbidities were collected using questionnaire surveys, and glycosylated hemoglobin (HbA1c), serum albumin (ALB) and hemoglobin levels were collected from medical records. The nutrition status was assessed with the new version of the Mini Nutritional Assessment Short Form (MNA-SF). Factors affecting the development of malnutrition were among the elderly T2DM patients identified using a multivariable logistic regression model. Results: A total of 382 elderly T2DM patients were enrolled, including 226 men (59.16%) and 156 women (40.84%) and with a mean age of (70.06±8.41) years. The prevalence of malnutrition was 22.25% among participants. Multivariable logistic regression analysis identified age (70 to 79 years, OR=1.261, 95%CI: 1.007-1.158; 80 years and older, OR=3.285, 95%CI: 1.618-6.662), three and more types of comorbidities (OR=2.790, 95%CI: 1.254-5.191), use of multiple medicines (OR=3.501, 95%CI: 1.841-6.658), sleep disorders (OR=1.613, 95%CI: 1.120-2.322), regular exercises (OR=0.280, 95%CI: 0.115-0.614), serum ALB of 35 g/L and greater (OR=0.272, 95%CI: 0.102-0.560) and HbA1c of 7% and higher (OR=2.914, 95%CI: 1.445-5.881) as factors affecting the development of malnutrition among elderly patients with T2DM. Conclusions The risk of malnutrition is associated with age, types of comorbidities, use of multiple medicines, sleep disorders, regular exercise, HbA1c and ALB among the elderly patients with T2DM. Periodical nutrition screening and intensified health education are recommended for T2DM patients.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To analyze the phenotype and genotype of two Chinese family with inherited dysfibrinogenemia and the molecular pathogenic mechanism.Methods:In the probands and their family members, coagulation routine, fibrinogen activity(Fg∶A) and fibrinogen antigen(Fg∶Ag) were detected . To find the mutation and exclude single nucleotide polymorphisms, all the exons and exons-intron boundaries of fibrinogen genes ( FGA, FGB and FGG) were amplified by Ploymerase Chain Reaction (PCR), then sequenced. Bioinformatics prediction softwares were used to predict and score the change of function caused by the variant. PyMol were used to analyze the structure of protein caused by the variant. Clustal X software was used to analyze the conservation of the mutant amino acids. Results:The thrombin time(TT) of the two was slightly prolonged and could not be corrected by protamine sulfate, and the fibrinogen activity was significantly reduced (1.25 g/L and 1.17 g/L), but the fibrinogen antigen content was normal, respectively (3.50 g /L and 3.81 g/L). Genetic analysis showed that both probands were heterozygous missense variants( FGB exon 7 c. 1115 T>A (p.Val372Glu)), both of which originated from the paternal line. The prediction results of the four bioinformatics softwares indicate that this variant could be disease causing. Clustal X software showed that Val372 is highly conserved among homologous species. Based on the guidelines of the American College of Medical Genetics and Genomics, c. 1115 T>A was predicted to be likely pathgenic(PM2+ PP1+ PP2+ PP3+ PP4). PyMol shouwed p. Val372Glu variant changes the secondary structure and three-dimensional structure of fibrinogen protein were changed caused by p. Val372Glu variant. Conclusion:Inherited dysfibrinogenemia of the probands maybe caused by variant of FGB c. 1115 T>A(p.Val372Glu), and the variant was firstly reported.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

Objective: To analyze the characteristics of stress symptoms before and after surgery in adolescent idiopathic scoliosis (AIS) patients and their correlation with postoperative pain. Methods: Fifty-four AIS patients aged 13-18 years from January 2015 to June 2018 in Foshan Traditional Chinese Medicine Hospital were selected. The anxiety, stress and stress symptoms of the patients before and 6 months after operation were assessed by the Trauma Symptom Checklist for Children-Alternative version (TSCC-A) and the Youth Self-Report (YSR). The pain was assessed by Visual Analogue Scale. The correlation between the stress symptoms of the patients and postoperative pain were analyzed by linear regression equation. Results: The score of anxiety/depression and internalization problems in YSR before operation was (5.40±2.48) and (12.19±4.67) respectively, and 6 months after operation, the score was (4.10±1.92) and (9.81±3.46) respectively, there were significant differences between preoperative and 6 months after operation (t value was 7.266, 8.107, P < 0.05). Before operation, the scores of anger in TSCC-A, the scores of social problems and attention problems in YSR were positively correlated with postoperation pain (P < 0.05), while postoperation pain was positively correlated with the scores of anxiety in TSCC-A, the scores of social problems and attention problems in YSR 6 months after operation (P < 0.05). Conclusions Preoperative stress symptoms of AIS patients are associated with postoperative pain, while postoperative pain is associated with postoperative recovery anxiety. Preoperative intervention should be actively taken to reduce perioperative stress symptoms and postoperative pain, so as to further improve the quality of nursing.

OBJECTIVE: To explore molecular etiology and clinical characteristics of two pedigrees affected with hereditary factor VII(FVII) deficiency. METHODS: The nine exons and flanking sequences of the F7 gene of the probands were amplified by PCR. The amplicons were analyzed by direct sequencing. Suspected mutations were subjected to SWISS-MODEL modeling and analysis of protein structure change by Pymol software and conservation of amino acids across various species. RESULTS: For proband of pedigree 1, the prothrombin time (PT), FVII activity (FVII:C) and FVII antigen (FVII:Ag) were 36.3 s, 3%, 53.56%, respectively. Sequencing revealed a compound heterozygous variants of c.80_81delCT and c.1371G>T(p.Arg439Ser). His son carried a heterozygous c.1371G>T (p.Arg439Ser) variant. For proband of pedigree 2, the PT, FVII:C and FVII:Ag were 22.3 s, 4%, 1.58%, respectively. Sequencing has revealed a compound heterozygous c.278G>T(p.Arg75Met) missense variant in exon 3 and c.1278T>G (p.His408Gln) in exon 9 of the F7 gene. His mother and son both carried a heterozygous c.278G>T(p.Arg75Met) variant. Three-dimensional simulation and homology analysis revealed that the p.Arg439Ser and p.Arg75Met can respectively alter part of hydrogen bonds and two highly conserved amino acids. CONCLUSION Two novel heterozygous missense variants of the F7 gene [c.1371G>T(p.Arg439Ser) and c.278G>T(p.Arg75Met)] probably account for the decrease of factor VII in the two pedigrees.
Asian Continental Ancestry Group ; Factor VII ; Factor VII Deficiency ; Genotype ; Heterozygote ; Humans ; Mutation ; Pedigree

Sepsis is now defined as life-threatening organ dysfunction due to a dysregulated host response to infection.The identification of pathogen is usually time-consuming.Besides, it has a low positivity rate in diagnosis of sepsis.Thus, it’s crucial to find suitable biomarkers for early diagnosis , prognosis and evaluation of treatment effect of sepsis.This article reviews the diagnostic value of pro-inflammatory cytokines, anti-inflammatory cytokines,surface receptors of immune cells in nature immunity in sepsis.

Objective To explore the influence of fixed-foot stance Yunshou combined with raising handclasp of Bobath on the recovery of upper extremity in post- stroke patients with hemiplegia. Methods Meeting the criteria 59 cases of stroke patients with hemiplegia were randomly divided into experimental group (29 cases) and control group(30 cases) according to random number table.All the patients in both groups were received routine therapy and nursing,besides,the patients in the control group were given raising handclasp of Bobath,while the patients in experimental group were treated with fixed-foot stance Yunshou combined with raising handclasp of Bobath.The intervention were once a day,five days a week,lasting eight weeks.The Fugl-Meyer Assessment of Upper Extremity(FMA-UE)and Modified Barthel Index(MBI) as well as Simple Test for Evaluating Hand Function(STEF) were used to assess the patients′condition before,8 weeks after treatment respectively. Results After 8weeks intervention,the scores of FMA-UE,MBI,STEF were 40.69±8.67,76.89±1.79,59.31±7.89 and before intervention were 24.17 ± 11.98,57.14 ± 13.93,31.83 ± 5.41, the difference between the experimental group before and after intervention was statistically significant(t=13.222,8.755,18.311,P<0.01).At 8 weeks,the scores of FMA-UE, MBI, STEF in the control group were 35.47 ± 9.68,73.17 ± 2.82,49.47 ± 8.78, and were17.38 ± 4.10,37.38 ± 4.30, 74.62 ± 11.22 respectively before intervention,all the measures in control groups had significantly improved than those before training (t=-4.797, 7.372, 17.139, P<0.01).Score of FMA-UE and STEF in the experimental group were higher than those in the control group,and the difference was statistically significant (t=2.180, 4.525, P<0.05 or 0.01), while the MBI had no statistically difference between two groups (P>0.05). Conclusion Compared with training on raising handclasp of Bobath alone,fixed-foot stance Yunshou combined with raising handclasp of Bobath is more effective On the recovery of upper limb function in stroke patients with hemiplegia.

Objective To verify the infantile amnesia phenomenon and discuss the effect of rapamycin injection on infantile amnesia and hippocampal neurogenesis.Methods (1) In experiment one,17-day-old (P17) and 60-day-old (P60) male Sprague-Dawley rats (n=84) were trained in a passive-avoidance task (they were randomly sub-divided into the shocked group and non-shocked group);all rats were tested immediately,2 and 7 days after training for memory retention.(2) In experiment two,P17 rats (n=84) were randomly divided into three groups:vehicle group,20 mg/kg rapamycin group and 40 mg/kg rapamycin group (they were sub-divided into the shocked group and non-shocked group);P17 rats were immediately injected with either vehicle or rapamycin after passive-avoidance training,and memory retention was evaluated 2 and 7 days after training.(3) In experiment three,P1 7 rats (n=48) were randomly divided into four groups:normal group,vehicle group,20 mg/kg rapamycin group and 40 mg/kg rapamycin group;immunofluorescence staining of BrdU/DCX was detected to observe the hippocampal neurogenesis at post-natal day 19 (P19) and post-natal day 24 (P24) after vehicle or rapamycin injection at P17 rats.Results In experiment one,P17 and P60 shocked rats exhibited comparable levels of crossing latencies when being tested immediately (P＞0.05),when being tested after 2 days and 7 days,P17 rats forgot more rapidly than P60 rats (P＜0.05);there were no age-related differences in crossing latencies between the non-shocked groups (P＞0.05).In experiment two,three shocked groups exhibited comparable levels of crossing latencies when being tested 2 days after training (P＞0.05),however,administration of rapamycin could enhance the memory retention 7 days after training;significant differences were noted between the vehicle group and each of the rapamycin treated groups (P＜0.05);there were no dose-related differences in crossing latencies among the non-shocked groups (P＞0.05).In experiment three,less BrdU-positive and BrdU/DCX-positive cells were found in the DG of the hippocampus at 20 mg/kg and 40 mg/kg rapamycin groups as compared with those in the vehicle group at P19 and P24 rats (P＜0.05).Conclusion The infantile amnesia phenomenon is verified,and rapamycin may enhance the memory retention in infant rats by reducing the hippocampal neurogenesis.