Objective To evaluate the value of rs61330082 and rs4730153 polymorphisms of Visfatin locus for the diagnosis of type 2 diabetes mellitus(T2DM)in a high-risk population.Methods SNPscanTM high-throughput single nucleotide polymorphism typing technique was used to genotype Visfatin gene loci rs61330082 and rs4730153 in 346 T2DM patients(T2DM group)and 1426 normal controls(NC group).Logistic regression analysis was used to analyze T2DM risk factors.ROC curves were used to analyze the optimal cut-off values of Visfatin gene rs61330082 and rs4730153 for the diagnosis of T2DM.Results The proportion of women,age,obesity,smoking,hypertension,FPG,HbA1c and TG were higher in T2DM group than those in NC group(P<0.01)and HDL-C was lower than in NC group(P<0.01).The frequency of G allele and GG genotype was higher in T2DM group compared with NC group(P<0.05).Logistic regression analysis showed that age,female,obesity,hypertension,TG,and GG genotype at rs4730153 locus were risk factors for T2DM,HDL-C was a protective factor for T2DM.The area under the ROC curve of GG genotype at Visfatin rs4730153 mutation for diagnosis of T2DM was 0.668 and the optimal cut-off point for predicting T2DM was 20.04%,with sensitivity 60.1%and specificity 66.1%,respectively.Conclusion The GG genotype of Visfatin gene rs4730153 locus is associated with the risk of T2DM and can beused as a candidate gene for predicting phenotype of T2DM.

Aortic aneurysm and dissection are critical cardiovascular diseases that threaten human life and health seriously. No pharmacological treatment can effectively prevent disease progression. The imbalance of aortic wall cells and non-cellular components leads to structural or functional degeneration of the aorta, which is a prerequisite for disease occurrence. As the important non-cellular component, extracellular matrix (ECM) is crucial to maintain the aortic structure, function, and homeostasis. Abnormal production of elastin and collagen, destruction of cross-linking between elastic fibers and collagen fibers, and the imbalance of metalloproteinase and inhibitors leads to excessive degradation of ECM proteins, all of which have destroyed the structure and function of aorta. It will provide more ideas for disease prevention and treatment by learning ECM proteins and their metabolic mechanism. Here, we focus on the ECM proteins that have been reported to be involved in aortic aneurysm and dissection, and discuss the regulatory mechanism of metalloproteinase and inhibitors.

Objective To investigate the effect of the glutathione peroxidase 4(GPx4)on mouse so-matic cell reprogramming.Methods To compare the expressions of GPx4 in OG2 mouse embryonic fibroblast(OG2-MEF)cells(MEFs group)and mouse embryonic stem cells(mESC,mESCs group),the expression lev-el of intracellular GPx4 was determined by transcriptome sequencing technique and Western blot.To verify the effect of GPx4 on the efficiency of the somatic cells reprogramming,the complete open reading frame se-quence of GPx4 gene and its selenocysteine insertion sequence(SECIS)were connected to the retroviral vector pMXs for constructing the overexpressed plasmid pMXs-GPx4.Gpx4-targeting short hairpin RNA(shRNA)was synthesized and connected to pSUPER vector,GPx4 shRNA1 and GPx4 shRNA2 were constructed to knockdown GPx4 expression.The above plasmids were co-transfected with pMXs-Sox2,pMXs-Klf4 and pMXs-Oct4 into MEF cells for reprogramming induction to obtain the pMXs no-load control group(pMXs NC),pMXs GPx4 group,pSUPER no-load control group(pSUPER NC),GPx4 shRNA1 group and GPx4 shRNA2 group.The expressions of GPx4 gene and multifunctional marker genes Rex1,Sox2,Dappa3,Sall4,Oct4 and Nanog were detected by real-time fluorescence quantitative PCR.The induced pluripotent stem cells(iPSC)were detected by immunofluorescence staining;the number of iPSC clones generation was detected by alkaline phosphatase staining of pluripotent stem cells;the GPx4 protein expression was detected by Western blot.Results The mRNA and protein expression of GPx4 in the mESCs group was higher than that in the MEFs group;compared with the pMXs NC group,the expression level of GPx4 mRNA in the pMXs GPx4 group was significantly increased;compared with the pSUPER NC group,the GPx4 mRNA and protein levels in the GPx4 shRNA1 group and GPx4 shRNA2 group were decreased(P＜0.05);the iPSC clone number in the pMXs GPx4 group was higher than that in the pMXs NC group,but the difference was not statistically significant(P＞0.05).The number of iPSC clones in the GPx4 shRNA1 group and GPx4 shRNA2 group was significantly lower than that in the pSUPER NC group,and the difference was statistically significant(P＜0.05).After completing the reprogramming,compared with the original MEF cells,the expression levels of various pluripotent marker genes Rex1,Sox2,Dappa3,Sall4,Oct4 and Nanog in the generated iPSC of each group were increased.Conclusion GPx4 knockdown could inhibit the efficiency of somatic cell reprogram-ming,its generated induced pluripotent stem cells have the normal pluripotent gene expression ability.

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.

At present,the commonly used clinical protocols of oral comestic restoration are mostly based on the aes-thetic indicators proposed by Western developed countries(referred to as Western aesthetics).Mechanically copying the Western aesthetic scheme,ignoring the difference between it and the Chinese oral aesthetic indicators(referred to as Chinese aesthetics),is unable to effectively support personalized cosmetic restoration diagnosis and treatment.In addition,new technologies and new solutions for cosmetic restoration,which are developing rapidly in recent years,are emerging one after another,but many popular concepts are confusing and lack of proper hierarchical diagnosis and treatment norms,and there is indeed an urgent need for discussion and clarity.From the perspective of serving clinical application,this paper discusses the deficiencies of the Chinese translation of the word"aesthetics",the diffe-rence and connection between aesthetics and cosmetolo-gy,and the relationship between cosmetic restoration and fixed restoration.It also discusses the difference be-tween anterior teeth,esthetic zone and exposed zone,the diagnostic and therapeutic value of oral aesthetic analysis,as well as the application methods of desensitization,suggestion,and other therapies in difficult oral cosmetic restoration cases.We further introduce the decision tree and the clinical pathway for restoration and reconstruction of teeth in ex-posed zone guided by aesthetic analysis,and introduce the clinical process of aesthetic analysis and evaluation,the clinical triclassification of oral cosmetic restoration,and the corresponding clinical classification diagnosis and treat-ment points.

At present,the commonly used clinical protocols of oral cosmetic restoration are mostly based on the oral aesthetic indexes proposed by Western developed countries(referred to as Western aesthetics),which are different from the oral aesthetic indexes unique to Chinese people(referred to as Chinese aesthetics).In the design of restoration schemes and the evaluation of restoration effects,these differences have a large or small effect on the doctor-patient-tech-nology triad.Improper handling could directly weaken the cooperation efficiency of the three parties,reduce patient satis-faction,and even lead to medical disputes in serious cases.From doing a good job of oral cosmetic restoration in China,the connotative characteristics of Chinese oral aesthetics are introduced in this paper,and the value of oral aesthetic anal-ysis in diagnosis and treatment is discussed.The process and method of aesthetic analysis and assessment through the modified Chinese psychosocial impact of dental aesthetics questionnaire and the evaluation ruler of the expected value of oral cosmetic restoration are further introduced in detail.

Objective To provide a scientific basis for the prevention and control of rheumatoid arthritis(RA)in China by analyzing the current status and trend of disease burden in China from 1990 to 2019.Methods The incidence,prevalence,mortality,and disability adjusted life years of RA from 1990 to 2019 were analyzed based on GBD data.DALYs and other indicators,and comparative analysis of the annual development trend of the levels in China,the United States,Japan and the world through the scaling rates of the four indicators.Results In 2019,the incidence,prevalence,mortality,DALYs rate and standardized rate of RA in China were higher in females than in males,and the mortality rate increased with age,and peaked in the age group over 95 years old.The incidence rate,prevalence rate and DALYs rate increased firstly and then decreased with theincrease of age,and reached the peak in age group 60～,70～and 85～years old,respectively.From 1990 to 2019,the incidence,prevalence,mortality and DALYs of RA in China showed an increasing trend.After eliminating the differences in population age composition,the standardized incidence and prevalence of RA in China showed an increasing trend.The normalized RA mortality rate and the normalized DALYs rate showed a steady trend in China.In 2019,the normalized incidence,prevalence and DALYs of RA in China were lower than those in Japan,the United States and the world.In 2019,the standardized mortality rate was higher than that of Japan,the United States and the world.Conclusion In the past 30 years,the disease burden of RA in China has been on the rise.It is necessary to strengthen the publicity and education of RA prevention and control,especially the prevention and control of middle-aged and elderly women,and formulate reasonable policies to further reduce the disease burden of RA in China.

Objective:To evaluate the changes of ventricular function in the twin-to-twin transfusion syndrome (TTTS) fetuses before and after fetoscopy laser photocoagulation (FLP) by fetal heart qualifiction (fetal HQ) technology.Methods:A total of 30 TTTS pregnant women who underwent FLP and delivered in the Third Affiliated Hospital of Zhengzhou University from January 2023 to November 2023 were prospectively selected as the TTTS group, including 30 donor fetuses and 30 recipient fetuses. The control group included 34 normal monochorionic diamniotic (MCDA) twins (68 fetuses) at the same gestational age. The changes of cardiac function of donor and recipient fetuses before and one day, one week and one month after FLP treatment were investigated by fetal HQ. The correlations between stage and global strain(GS) and fractional area change(FAC) of ventricle were analyzed. The inter-observer and intera-observer repeatability tests were performed.Results:①Before FLP treatment, fractional shortening(FS)10-24 of left ventricle and FS10-11 of right ventricle in donor group were lower than the control group (all P<0.05).GS, FAC, FS10-24 of left ventricle and GS, FAC, FS1-24 of right ventricle in recipient group were lower than the control group (all P<0.05). In the donor group, Quintero stage was moderately positively correlated with GS of right ventricle and moderately negatively correlated with FAC of right ventricle ( rs=0.535, -0.515; P=0.004, 0.006). But there were no correlation between Quintero stage and GS and FAC of left and right ventricle in recipient group (all P>0.05). ②After FLP treatment, the left ventricular systolic function of the donor group recovered to the normal level one day after operation ( P>0.05). But the FS16-24 of left ventricle were lower than the control group one week after operation, and the FS21-24 of left ventricle were still lower than the control group one month after operation(all P<0.05). One day after operation, the systolic function of the right ventricle in the donor group decreased, and GS, FAC and FS6-24 of the right ventricle were lower than the control group (all P<0.05). However, the right ventricular systolic function recovered to the normal level one week after operation ( P>0.05). ③After FLP, the systolic function of left ventricle and right ventricle recovered in recipient group, especially for right ventricle. One month after operation, only FS12-16 of left ventricle were lower than the control group ( P<0.05). But GS and FAC of left and right ventricle and 24 segments FS of right ventricle recovered to the control level (all P>0.05). ④The ICC of left and right ventricular parameters were greater than 0.75, indicating good repeatability ( P<0.05). Conclusions:Fetal HQ technology can sensitively evaluate fetal heart function in TTTS fetuses with good repeatability. Before FLP, the ventricular function of donor and recipient fetuses are affected to varying degrees.After FLP, the left and right ventricular function of the donor and recipient fetuses are improved to varying degrees and have different recovery rules.

Objective:To verify the feasibility and advantages of ARCHER-NM, a GPU-based fast Monte Carlo (MC) dose calculation engine, in calculating individualized doses of radiopharmaceutical therapy (RPT) through simulation experiments.Methods:The calculation reliability and efficiency of ARCHER-NM were verified by comparing its result with those of the MC software GATE in the water phantom experiments of radionuclide point sources and the dose calculations for RPT-treated patients. In the water phantom experiments, the generality of ARCHER-NM on different radionuclides was verified using common radionuclides like 67Cu, 89Sr, 90Y, 131I, 177Lu, and 188Re. The calculations of individualized doses for RPT-treated patients were tested based on the data of two patients from the University of Michigan′s public dataset for 177Lu-DOTATATE-treated cases. Gamma passing rates, dose volume histograms (DVHs), and average organ doses were employed to assess the consistency of ARCHER-NM and GATE in patients′ dose calculation result. The computing time was statistically analyzed to assess the efficiency of MC calculations. Results:In the water phantom experiments for all radionuclides, the relative differences of average doses between ARCHER-NM and GATE ranged from -1.63% to 2.29%, with an average absolute difference of 1.15%, suggesting high consistency. As indicated by the dose result of the two patients, the average doses for all organs between ARCHER-NM and GATE exhibited percentage errors of below 4%. The gamma passing rates for the two patients were 98.8% and 98.6%, respectively, under the 2 mm/1% standard within the 3% maximum dose isodose line. The simulation of 5 × 10 9decay required 90 s for ARCHER-NM on a personal host configured with a 24 GB Nvidia Titan RTX, whereas GATE took over 9 h on a 112-thread server for the same simulation. Conclusions:The water phantom experiments substantiate the accuracy and generality of ARCHER-NM for dose calculations. Based on the organ dose calculations of 177Lu-DOTATATE-treated patients, ARCHER-NM proves accurate and quick in calculating the individualized internal doses for RPT-treated patients. Therefore, ARCHER-NM plays a positive role in the dose planning of subsequent treatment and the protection of organs at risk including kidneys.

Objective:To evaluate the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without ribavirin in the treatment of patients diagnosed with chronic hepatitis C (CHC) and chronic kidney disease (CKD).Methods:From June 2018 to May 2022, a total of 75 patients with CHC and CKD, and treated with SOF/VEL±ribavirin at the Kunming Third People′s Hospital were enrolled in this study. The basic information of patients were collected. Assessments of renal function, liver function, virologic response rate and adverse events were conducted at baseline, four weeks and 12 weeks of treatment and 12 weeks after treatment withdrawal. Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used for statistical analysis.Results:Among the 75 patients, 51 cases(68.0%) were classified as CKD stage 2, 12 cases (16.0%) as CKD stage 3, four cases (5.3%) as CKD stage 4, eight cases (10.7%) as CKD stage 5. Additionally, 26 cases (34.7%) were classified as HCV type 3a, while 37 cases (49.3%) were classified as type 3b. Among the patients, 51 cases (68.0%) had cirrhosis, including 15(20.0%) compensated cirrhosis and 36(48.0%) decompensated cirrhosis. Twelve weeks after treatment withdrawal, there was a statistically significant improvement in the estimated glomerular filtration rate (eGFR) compared to baseline (81.76(60.94, 94.34) mL/(min·1.73 m 2) vs 70.99(52.86, 82.38) mL/(min·1.73 m 2), Z=8.12, P=0.040). From baseline to 12 weeks after treatment withdrawal, eGFR of patients with CKD stage 2 and stage 3 were both gradually increased, with statistical significance ( H=8.91 and 8.03, respectively, both P<0.05). For CKD stage 2 patients, eGFR increased from 78.82(70.98, 84.80) mL/(min·1.73 m 2) to 86.94 (75.91, 96.01) mL/(min·1.73 m 2), while CKD stage 3 patients had an increased from 51.24 (45.92, 53.37) mL/(min·1.73 m 2) to 64.58 (44.54, 74.34) mL/(min·1.73 m 2). Renal function was improved to CKD stage 1 in 21 patients (28.0%). Compared to baseline, CKD stage 2 patients exhibited a decrease of aspartate aminotransferase to platelet ratio index 12 weeks after treatment withdrawal, and alanine aminotransferase and aspartate aminotransferase levels were also significantly improved with statistical significance ( Z=8.03, 21.57 and 43.74, respectively, all P<0.05). The rate of sustained virological response (SVR)12 at 12 weeks after treatment withdrawal was 98.7%(74/75). Among these cases, 51 patients in CKD stage 2, 11 patients in CKD stage 3, 12 patients in CKD stage 4 and stage 5 reached SVR12. Adverse events occurred in 32 patients (42.7%), including 18 cases of mild hemolytic anemia, four cases of skin itching, three cases of rash, two cases of chest tightness, and five cases of fatigue. Conclusions:SOF/VEL with or without ribavirin for the treatment of patients with CHC and CKD has good effectiveness and safety. The renal function, liver function and liver fibrosis degree have been improved after antiviral treatment.