[Summary]_ Severe hypertriglyceridemia is the third common cause of acute pancreatitis following after alcohol abuse and cholelithiasis. Moreover, it is also an important risk factor of cardiovascular events. However, the cases of severe hypertriglyceridemia caused by autoimmune disease were rare in clinical, which would bring the difficulty for diagnosis and treatment. A better understanding of the clinical characteristics, possible pathogenesis, and corresponding therapy of the disease would be helpful, which would reduce the risk of complications, and finally improve both the survival rate as well as quality of life of these patients.

[Summary] In newly diagnosed diabetic patients, fasting plasma glucose, HbA1C , and plasma lipid profiles were measured to analyze the association between HbA1C and plasma lipid profiles. HbA1C might affect plasma lipid profiles in newly diagnosed diabetic patients. Higher HbA1C was associated with the worse plasma lipid profiles and more severe insulin resistance.

Objective To analyze recent 30 years’ regularities in point selection for acupuncture treatment of Parkinson disease and provide reference for its treatment. Methods Parkinson disease, parkinsonism and acupuncture were used as key words. Recent 30 years’ Chinese literature was searched using Wanfang, CNKI, VIP and Chinese biomedical literature database. Selection of main acupoints and scalp acupuncture points, syndrome differentiation-based point selection and meridian tropism of main acupoints were metrologically studied. Results The Du meridian, the large intestine meridian and the gallbladder meridian were mainly selected for acupuncture treatment of Parkinson disease. Taichong(LR3), Baihui(GV20), Hegu(LI4) and Fengchi(GB20) were used as main points. Chorea-tremor control area, motor area and parietotemporal anterior oblique line were often selected as main scalp acupuncture points. Fenglong (ST40), Qihai(CV6), Sanyinjiao(SP6), Yinlingquan(SP9) and Zusanli(ST36) were often used according to syndrome differentiation-based point selection. Conclusion Modern acupuncture doctors select Taichong(LR3), Baihui(GV20), Hegu(LI4) and Fengchi(GB20) as main points, often use scalp acupuncture points and combine points mainly from the Du meridian according to syndrome differentiation in the treatment of Parkinson disease.

Objective To explore the correlation between the triglyceride glucose-waist-to-height ratio (TyG-WHtR) and advanced cardiovascular-kidney-metabolic (CKM) syndrome. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 were used and analyzed, including a total of 14 322 adult participants. The CKM syndrome is classified into 5 stages, with stages 0-2 categorized as the early phase and stages 3-4 as the advanced phase, which were subjected to dichotomous classification analysis. The TyG-WHtR was calculated using triglycerides, glucose, waist circumference, and height. Multivariate logistic regression was used to analyze the correlation between TyG-WHtR and advanced CKM syndrome, adjusting for variables such as age, sex, race, education level, poverty-income ratio (PIR), smoking status, and alcohol consumption. Restricted cubic spline (RCS) analysis was conducted to evaluate the nonlinear relationship between the TyG-WHtR and advanced CKM syndrome. Results Among the 14 322 participants, advanced CKM syndrome accounted for 16.99%. The TyG-WHtR level in the advanced CKM syndrome group was significantly higher than that in the early CKM syndrome group (5.60±0.03 vs 5.02±0.02, P＜0.001). Logistic regression showed that TyG-WHtR was an independent related factor for advanced CKM syndrome (OR＝1.48, 95%CI 1.36-1.61, P＜0.001). Subgroup analyses revealed that the TyG-WHtR was consistently associated with advanced CKM syndrome across different sex, rase, and age groups, with no significant interaction effects observed. RCS analysis revealed a nonlinear positive association between TyG-WHtR and advanced CKM syndrome (P_overall＜0.001, P_nonlinear＝0.014). When the TyG-WHtR exceeded 5, the risk of advanced-stage CKM syndrome showed a significant elevation. Conclusions The TyG-WHtR is an independent related factor for advanced CKM syndrome, with a particularly significant risk increase when TyG-WHtR exceeds 5.

Objective To evaluate myocardial microvascular lesions in patients with type 2 diabetes mellitus(T2DM)by 2D-speckle tracking echocardiography(2D-STE)and myocardial contrast echocar-diography(MCE).Methods A total of 45 T2DM patients admitted to the Endocrine Department of The First Affiliated Hospital of Air Force Military Medical University from August to November 2022 were enrolled in this study.All the patients were divided into two groups:simple T2DM group(n=22)and T2DM with microvascular complication group(MIC,n=23).In addition,24 healthy subjects were included as normal control(NC)group.2D-STE obtained the global longitudinal strain(GLS)and global circumferential strain(GCS);MCE obtained the average acoustic intensity(A),perfusion slope(b)of left ventricular segment,then myocardial blood flow(Aβ)was calculated and compared between groups.Results Compared with NC group,GLS,GCS,β and Aβ were lower in T2DM and MIC group(P＜0.05).Among the parameters of 2D-STE and MCE,GLS and Aβ have high diagnostic performance(P＜0.05)and GCS and β have medium diagnostic performance(P＜0.05).ROC curve analysis showed that the early warning values of myocardial microcirculation disorders were-17.63%(GLS),-21.55%(GCS),0.845 s-1(β),7.045 dB/s(Aβ)in patients with T2DM.Conclusion The mechanical strain and perfusion of myocar-dium in T2DM patients have already decreased even no lesion was shown in the peripheral micro-vessels.2D-STE combined with MCE can assess the changes of myocardial elasticity and microcirculation in T2DM in real time,which is helpful for early clinical diagnosis of diabetes cardiomyopathy and intervention guidance.

OBJECTIVE: To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function. METHODS: Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization. RESULTS: The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene. CONCLUSION The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.
DNA Mutational Analysis ; Female ; Frameshift Mutation ; HEK293 Cells ; HeLa Cells ; Humans ; Male ; Pedigree ; Polycystic Kidney, Autosomal Dominant/physiopathology* ; Protein Kinases/genetics* ; Protein Transport/genetics* ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation and speech delay. METHODS: Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy. RESULTS: The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c.5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c.56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c.5314dupA variant of the KAT6A gene in the fetus. CONCLUSION The heterozygous c.5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.
Child ; Humans ; Male ; Pregnancy ; Histone Acetyltransferases ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.
China ; Female ; Humans ; Mutation ; Pedigree ; Polydactyly/genetics* ; Thumb ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for a Chinese patient with amyotrophic lateral sclerosis (ALS). METHODS: Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Genetic variant was identified by whole exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and healthy controls. RESULTS: The patient was found to harbor a heterozygous c.420C>G (p.Asn140Lys) variant of the SOD1 gene. The same variant was not detected in his parents and 100 healthy controls. The variant has not been included in HGMD, dbSNP and other databases. CONCLUSION The c.420C>G variant of the SOD1 gene may underlie the ALS in this patient. Above finding has enriched the spectrum of SOD1 gene variants.
Amyotrophic Lateral Sclerosis/genetics* ; China ; Heterozygote ; Humans ; Superoxide Dismutase-1/genetics* ; Whole Exome Sequencing

Objective To investigate the effect of fenofibrate on glucolipid metabolism and insulin sensitivity in lipoprotein lipase heterozygous knockout ( LPL+/-) mice, and to explore its mechanism. Methods LPL+/- mice and wild type ( WT) C57 mice were selected and divided into 3 groups ( n=6 each group):LPL+/-( FB) group, LPL+/-(W)group,andWTgroup.MiceinLPL+/-(FB)groupweregavagedwithfenofibrate(50mg·kg-1·d-1)for8 weeks. Mice in LPL+/-( W) and WT groups were orally fed with the same volume water as that in LPL+/-( FB) group for 8 weeks. Body weight was observed. Plasma triglyceride ( TG ) and free fatty acid ( FFA ) were measured. Intraperitoneal glucose tolerance test in 3 groups of mice were performed. The glucose area under the curve ( AUCG) and homeostasis model assessment for insulin resistance index ( HOMA-IR) were calculated. Insulin-stimulated Ser473 Akt phosphorylation in liver and skeletal muscle was measured by Western blot. Reactive oxygen species ( ROS) levels in liver and skeletal muscle were determined by dihydroethidium staining method and superoxide dismutase ( SOD) and catalase ( CAT) mRNA expression levels were detected by real-time PCR. Results Compared with LPL+/-( W) mice, body weight of LPL+/-( FB) mice was lowered, plasma TG and FFA levels were decreased by about 46.0％and 76.5％respectively, and fasting insulin level and HOMA-IR were decreased while there were no significant differences in fasting glucose level and AUCG between two groups. Insulin-stimulated Ser473 Akt phosphorylation levels in liver and skeletal muscle of LPL+/-mice were enhanced by fenofibrate. ROS level in skeletal muscle of LPL+/-( FB) mice was lower than that in LPL+/-( W) mice while there was no significant difference in ROS of liver between two groups. Fenofibrate significantly increased SOD and CAT mRNA expressions in skeletal muscle of LPL+/-mice, but not in liver. Conclusion Fenofibrate reduces body weight, ameliorates lipid metabolism, and improves insulin sensitivity in LPL+/- mice, with reduced oxidative stress.