OBJECTIVE To investigate the effects of alirocumab combined with atorvastatin on clinical efficacy and safety of patients with acute coronary syndrome （ACS） who underwent percutaneous coronary intervention （PCI）. METHODS A total of 207 patients with ACS who underwent PCI in our hospital from January 2021 to December 2023 were randomly divided into alirocumab group， ezetimibe group and control group， with 69 cases in each group. All patients received routine thrombosis prevention and antihypertensive treatment after PCI. On this basis， patients in the control group were treated with atorvastatin （20 mg/time， once a day）； patients in the ezetimibe group were treated with ezetimibe （10 mg/time， once a day） + atorvastatin （20 mg/time， once a day）； patients in the alirocumab group were treated with alirocumab （75 mg/time， once every 2 weeks） + atorvastatin （20 mg/time， once a day）. All patients in the three groups were treated for 8 weeks and followed up for another 6 months after treatment. The levels of cardiac function and lipid metabolism indices before and after treatment， as well as the occurrence of major adverse cardiovascular event （MACE） and other adverse drug reaction （ADR） during the follow-up period were compared among the three groups. RESULTS After treatment for 8 weeks， the levels of cardiac function and lipid metabolism indices in the three groups were significantly improved compared with those before treatment （P＜0.05）. Compared with the control group and ezetimibe group， the left ventricular ejection fraction in the alirocumab group was significantly increased， and the left ventricular end-diastolic diameter （LVEDD） was significantly shortened （P＜0.05）. Compared with control group， LVEDD of ezetimibe group was significantly shortened （P＜0.05）， the levels of total cholesterol， triglyceride and low-density lipoprotein cholesterol in the alirocumab group and ezetimibe group were significantly decreased （P＜0.05）. During the follow-up period， there was no significant difference in the total incidence of MACE and the total incidence of other ADR such as headache and abdominal pain among the three groups （P＞0.05）. CONCLUSIONS Alirocumab combined with atorvastatin can significantly improve cardiac function and regulate lipid metabolism indices in patients with ACS after PCI without increasing the risk of MACE or other ADR.

Objective:To explore the genetic etiology of a child with primary hypertrophic osteoarthropathy(PHO).Methods:A child who was admitted to Zhongnan Hospital of Wuhan University on July 27, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing. Suspected splicing variant was verified by Sanger sequencing of family members. In vitro function was validated through a minigene assay, whilst the suspected exonic deletion was validated by long-fragment PCR. This study was approved by the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-011). Results:Whole exome sequencing revealed that the child has harbored compound heterozygous variants of HPGD gene, including a heterozygous deletion (Exon 3 del) derived from his father and a splicing variant (c.421+ 1G>T) derived from his mother. Long-fragment PCR verified that the child and his father had both harbored a 7 565 bp heterozygous deletion (c.218-1304_324+ 6156del), whilst the minigene assay proved that the splicing variant has resulted in skipping of exon 4. Conclusion:The heterozygous c. 218-1304_324+ 6156del deletion and the c. 421+ 1G>T splicing variant of the HPGD gene probably underlay the pathogenesis in this child. Above finding has enriched the mutational spectrum of the HPGD gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

Aim To analyze the risk factor of the cardiac rupture(CR)in patients with acute ST-segment eleva-tion myocardial infarction(STEMI).Based on this,the nomogram model of acute STEMI patients with CR was estab-lished.Methods Through Ningxia Medical University General Hospital's big data research platform and hospital in-formation system retrieval,5 412 patients with acute STEMI from January 2015 to December 2019 were continuously includ-ed in the study,of which 91 patients with CR were included as CR group;5 321 patients non-combined with CR were in-cluded as non-CR group.LASSO regression,univariate and multivariate Logistic regression were used to analyze the risk factors of CR in patients with acute STEMI,and the CR nomogram predictive model was established.The nomogram mod-el was validated and evaluated by using receiver operating characteristic(ROC)curve,Hosmer-Lemeshow test and clinical decision curve analysis(DCA).Results LASSO regression results showed that age,female,hypertension history,first medical contact time,shock index,Killip grade,white blood cell count,d-dimer,lactic acid,anterior myocardial in-farction,β-blocker administration within 24 hours,angiotensin converting enzyme inhibitor/angiotensin receptor antagonist(ACEI/ARB)administration within 24 hours,emergency percutaneous coronary intervention(PCI)were 13 risk factors of CR(P＜0.05).The screened 13 risk factors were analyzed by univariate and multivariate Logistic regression,the results suggested that age,Killip grade,first medical contact time,white blood cell count,not undergoing emergency PCI and not taking ACEI/ARB drugs within 24 hours were the risk factors of CR in patients with acute STEMI.The acute STEMI with CR nomogram model was established according to the above 6 risk variables.The area under the ROC curve before and after the internal verification of the nomogram model was 0.946(95％CI:0.927～0.961),0.947(95％CI:0.927～0.959),and the sensitivity was 0.957 and 0.904,respectively,the specificity was 0.858 and 0.876,respectively,which indicated that the model had good discrimination degree.The Hosmer-Lemeshow test showed that the deviation between the predicted value and the observed value was not statistically significant(x2=12.70,P=0.122),indicating that the no-mogram model had a good calibration.The DCA curve indicated that the predictive probability threshold of the model was from 0.00 to 0.40,and the clinical net benefit was the highest,indicating that the model had good clinical efficacy.Conclusion The nomogram model established in this study has better distinction,calibration and clinical effectiveness.It can effectively predict the probability of acute STEMI with CR,and provide some help for clinical diagnosis and treat-ment,so as to reduce the incidence of CR.

Objective To analyze the risk factors of cardiac rupture(CR)still occurrence after emer-gency percutaneous coronary intervention(PCI)in the patients with acute myocardial infarction(AMI).Methods The patients with AMI admitted and treated in this hospital from January 2017 to February 2021 were retrospectively analyzed.The patients with AMI who still developed CR after successful emergency PCI treatment were included in the CR group(n=27),and the patients with AMI who matched the gender,age,myocardial infarction location,acute ST-segment elevation myocardial infarction(STEMI)and successful e-mergency revascularization with the CR group according to the ratio of 1∶2,moreover without complicating CR served as the non-CR group(n=54).The gender,age,comorbidities,clinical indicators,laboratory indica-tors,drug use situation were collected for conducting the analysis.The univariate and multivariate logistic re-gression were used to analyze the risk factors of CR.Results There were no statistically significant differ-ences in the gender,age,comorbidities(hypertension,diabetes,hypercholesterolemia,old myocardial infarc-tion,old cerebral infarction,renal insufficiency,hyperuricemia)and myocardial infarction location between the two groups(P＞0.05).In the comorbidities,the incidence rate of atrial fibrillation in the CR group was higher than that in the non-CR group(25.9％vs.9.3％),and the difference was statistically significant(P＜0.05).The heart rate,serum creatinine,serum uric acid,N-terminal brain natriuretic peptide precursor(NT-proB-NP),cardiac troponin Ⅰ(cTnⅠ),proportion of no reflow in PCI,and the proportion of blood flow grade 3 in myocardial infarction thrombolysis test(TIMI)after PCI in the CR group were significantly higher than those in the non-CR group,while the proportions of systolic blood pressure,albumin,LVEF,use of β receptor block-ers and renin-angiotensin-aldosterone system(RAAS)inhibitors were lower than those in the non-CR group,and the differences were statistically significant(P＜0.05).Atrial fibrillation was an independent risk factor for CR(OR=3.06,95％CI:1.16-8.10,P＜0.05).High level of albumin(OR=0.93,95％CI:0.88-0.99,P＜0.05)and high level of LVEF(OR=0.92,95％CI:0.86-0.99,P＜0.05)were the independent protective factors for CR.Conclusion The occurrence of CR is correlated with multifactors,atrial fibrillation is an independent risk factor for CR,and the high levels of albumin and LVEF are the independent protective factors for CR.

Purpose To evaluate the effect of PCSK9 gene knockout on myocardial function in obese mice via ultrasound strain technology,and to discuss the related mechanisms.Materials and Methods Twenty six-week-old wild-type C57BL/6 male mice were selected and randomly divided into a normal group(n=10)and an obese group(n=10).Additionally,ten six-week-old PCSK9-/-C57BL/6 male mice were selected as the PCSK9-/-group.Mice in the obese group and PCSK9-/-group were fed with high-fat feed to create models,while those in the normal group were fed with regular feed.After 12 weeks,mice that were successfully modeled were selected from the obese group and PCSK9-/-group.Then,the three groups of mice were subjected to cardiac ultrasound,transmission electron microscopy and immunofluorescence staining to observe relevant indicators.Results The interventricular septal end-diastolic thickness of mice in obese group,normal group,and PCSK9-/-group were(0.98±0.13)mm,(0.77±0.07)mm,(0.78±0.13)mm,respectively,with statistically significant difference(F=5.10,P=0.02).The obese group was thicker than the normal group(t=2.73,P＜0.05),while the PCSK9-/-group was thinner than the obese group(t=-2.92,P＜0.05).There were statistically significant differences in global longitudinal strain and global circumferential strain of the left ventricle among the three groups(F=7.44,15.40,P＜0.05),with the obese group showing a decrease in global longitudinal strain and global circumferential strain compared to the normal group(t=3.79,5.50,P＜0.05).The PCSK9-/-group showed an increase in global longitudinal strain and global circumferential strain compared to the obese group(t=-2.53,-3.37,P＜0.05).Electron microscopy and immunofluorescence results showed that the myocardial ultrastructure of the obese group was damaged,and the expression of NLRP3 and Caspase-1 were higher than that of the normal group(t=12.53,-4.73,P＜0.05),the myocardial ultrastructure damage in the PCSK9-/-group was significantly improved,the expression of NLRP3 and Caspase-1 were lower than that in the obese group(t=-6.23,2.05,P＜0.05).Conclusion Ultrasound strain can more sensitively detect changes in myocardial function in obese mice with PCSK9 gene knockout compared with conventional cardiac ultrasound parameters.Knockout of the PCSK9 gene may improve myocardial function in obese mice by inhibiting the expression of NLRP3 and Caspase-1.

Objective To investigate the correlation between neuropeptide S receptor(NPSR)single nucleotide polymorphism(SNP)(rs323917,rs323920,rs323922,rs2530547,rs324957)and primary insomnia(PI).Methods A total of 157 patients diagnosed with PI in the outpatient department of Center of Sleep Medicine,Gansu Provincial People's Hospital from December 2016 to May 2019 were selected as PI group,and 133 healthy physical examination subjects during the same period were selected as control group.Venous blood samples were collected and DNA,polymerase chain reaction(PCR)amplification and agarose gel electrophoresis were extracted.rs323917,rs323920,rs323922,rs2530547,rs324957 single nucleotide loci were genotypized by target site sequencing.Meanwhile,standard polysomnosis monitoring was performed to analyze the correlation between gene polymorphism and PI.Results There were no significant differences in the genotype distribution of NPSR SNP sites(rs323917,rs323920,rs323922,rs2530547)and allele frequency and rs324957 allele frequency between two groups(P＞0.05).There was significant difference in genotype distribution of rs324957(P=0.034).There was no significant difference in the frequency of different haplotypes between two groups(P＞0.05).Conclusion The expression of rs324957 SNP genotypes in NPSR may be related to PI,and AG genotype is dominant.

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

‍Traditionally， the progression from compensated liver cirrhosis to decompensated liver cirrhosis has been considered an irreversible point in the natural history of the disease； however， with the suppression of underlying etiology， cure， and disease regression， this view is challenged by an increasing number of new evidence， and the idea of “recompensation of liver cirrhosis” is gradually being accepted. In recent years， scholars in China and globally have been exploring the specific definition of recompensation of liver cirrhosis and the clinical features of patients. By summarizing the recent studies on recompensation of liver cirrhosis in China and globally， integrating existing views， and analyzing related research evidence， this article points out the main challenges in the field of recompensation at this stage， including the lack of in－depth clinical and basic research， the need to define recompensation in the context of NAFLD， and related ethical issues， in order to provide new directions for future research in this field.

‍Nonalcoholic fatty liver disease （NAFLD） is a group of highly heterogeneous diseases closely associated with metabolic dysfunction. Sarcopenia is a syndrome caused by a continuous decline in muscle mass， strength， and function， and it is often accompanied by NAFLD. Insulin resistance is the main pathological mechanism for sarcopenia and NAFLD， and in addition， factors such as changes in proteins and branched‍-‍chain amino acid， hyperammonemia， intestinal flora， and endocrine dysfunction can also lead to sarcopenia and NAFLD. With the deepening of clinical research， many published prospective studies have confirmed the existence of a bidirectional and complex pathophysiological relationship between sarcopenia and NAFLD. This article reviews the bidirectional relationship between sarcopenia and NAFLD， discusses the common pathogenesis of sarcopenia and NAFLD， summarizes the challenges faced in this field， and proposes new directions for the research on the bidirectional relationship between NAFLD and sarcopenia.

OBJECTIVE: To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities. METHODS: A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay. RESULTS: WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3). CONCLUSION The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Male ; Pregnancy ; Exons ; Intellectual Disability/genetics* ; Mothers ; Mutation ; p21-Activated Kinases/genetics* ; Parents ; RNA Splicing