BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Hypertrophic cardiomyopathy (HCM) in children is one of the most common hereditary cardiomyopathies caused by gene mutations encoding cardiac carcomeric proteins. It is mainly characterized by ventricular hypertrophy and non-enlarged cardiac chambers, with a potential risk of sudden cardiac death. Usually, the assessment is based on the general condition, clinical symptoms, imaging examination results, family history, and genetic testing of the patients, thereby providing a basis for judging the risk of sudden cardiac death, and then identifying the risk factors for sudden cardiac death in hypertrophic cardiomyopathy. Based on the relevant domestic and foreign literature in recent years and the accumulated work experience in the department of cardiology of Beijing Children's Hospital, these risk factors are divided into major and minor risk factors. A comprehensive understanding of these risk factors can guide the clinical early warning of high-risk children with possible sudden death, which is helpful for more accurate assessment of the prognosis of hypertrophic cardiomyopathy in children and the implementation of targeted intervention. This article reviewed the research progress of related risk factors for the prognosis of hypertrophic cardiomyopathy in children.

Objective To investigate the predictive value of lactate/albumin ratio(LAR),interleukin-6(IL-6)and CD4+T lymphocyte count in 28-day mortality in patients with severe pneumonia and sepsis.Methods A total of 73 patients with severe pneumonia and sepsis admitted to the Respiratory Intensive Care Unit(RICU)of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2022 to June 2023 were enrolled and divided into the survival group(n=43)and the death group(n=30)according to their 28-day outcomes.The clinical data of the patients were collected from their electronic medical records,including age,gender,comorbidities with hypertension,diabetes,and coronary artery heart disease(CHD),as well as sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,mean arterial pressure(MAP),confusion,uremia,respiratory rate,blood pressure,age ≥65 years(CURB-65)score,total bilirubin(Tbil),serum creatinine(Scr),platelet count(PLT),white blood cell(WBC)count,procalcitonin(PCT),and C-reactive protein(CRP)at admission to RICU.On the 1st,3rd,and 7th day after admission to RICU,the patients'arterial blood was drawn,and the lactate level was detected by a fully automated blood gas analyzer.The peripheral venous blood was drawn,and the serum albumin and IL-6 levels were detected by enzyme-linked immunosorbent assay,and the CD4+T lymphocyte subset count was measured by flow cytometry.The LAR of patients on the 1st,3rd and 7th day was calculated.The clinical data of the patients and the LAR,IL-6 level and CD4+T lymphocyte count on the 1st,3rd,and 7th day were compared between the two groups.The influencing factors of 28-day mortality in patients with severe pneumonia and sepsis were analyzed by logistic regression,and the predictive value of each influencing factor on the 28-day mortality in patients with severe pneumonia and sepsis was evaluated by the receiver operating characteristic(ROC)curve.Results There was no significant difference in gender,age,proportions of comorbidities with hypertension,diabetes and CHD,length of stay in RICU,and Tbil,MAP,PLT,Scr,WBC,PCT and CRP at admission to RICU(P＞0.05).The APACHE Ⅱ and CURB-65 scores of the patients in the death group were significantly higher than those in the survival group(P＜0.05).On the 1st,3rd and 7th day,the CD4+T lymphocyte count in the death group was significantly lower than that in the survival group,while the SOFA score was significantly higher than that in the survival group(P＜0.05).On the first day,there was no significant difference in the LAR and IL-6 level be-tween the death group and the survival group(P＞0.05).However,on the 3rd and 7th day,the LAR and IL-6 level in the death group were significantly higher than those in the survival group(P＜0.05).The LAR,IL-6 level and SOFA score on the 3rd and 7th day in the survival group were significantly lower than those on the 1st day,and these indicators on the 7th day were sig-nificantly lower than those on the 3rd day(P＜0.05);the CD4+T lymphocyte count on the 3rd and 7th day was significantly higher than that on the 1st day(P＜0.05),while it showed no significant difference on the 7th and 3r day(P＞0.05).The IL-6 level on the 7th day in the death group was significantly lower than that on the 1st and 3rd day(P＜0.05),while there was no significant difference in IL-6 level on the 1st day compared with the 3r day(P＞0.05);moreover,there was no significant difference in LAR,CD4+T lymphocyte count and SOFA score between each time point(P＞0.05).Pearson correlation analy-sis showed that on the 3rd day,the LAR and IL-6 level were significantly positively correlated with the SOFA score in patients with severe pneumonia and sepsis(r=0.385,0.394;P＜0.05).On the 7th day,the LAR and IL-6 level were also significantly positively correlated with the SOFA score(r=0.418,0.402;P＜0.05).On the 3 rd and 7 th day,CD4+T lymphocyte count was significantly negatively correlated with the SOFA score(r=-0.451,-0.454;P＜0.05).Logistic regression analysis showed that the APACHE Ⅱ score,LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day,and the IL-6 level and CD4+T lym-phocyte count on the 7th day were the influencing factors for 28-day mortality in patients with severe pneumonia and sepsis(P＜0.05).The ROC curve showed that the APACHE Ⅱ score,LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day and the combination of the three,IL-6 level and CD4+T lymphocyte count on the 7th day and the combination of the two had certain predictive value for the 28-day mortality in patients with severe pneumonia and sepsis(P＜0.05).The area under the ROC curve(AUC)of LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day combined to predict 28-day mortality in patients with severe pneumonia and sepsis was 0.891,and the AUC of APACHE Ⅱ score for predicting 28-day mortality in pa-tients with severe pneumonia and sepsis was 0.769.The AUC values of LAR,IL-6 level and CD4+T lymphocyte count on the 3rd day for predicting 28-day mortality in patients with severe pneumonia and sepsis were 0.795,0.757 and 0.770,respective-ly,and the AUC values of IL-6 level and CD4+T lymphocyte count on the 7th day and their combination for predicting 28-day mortality in patients with severe pneumonia and sepsis were 0.743,0.802 and 0.888,respectively.Conclusion The 3-day LAR,IL-6 level and CD4+T lymphocyte count,and the 7-day IL-6 level and CD4+T lymphocyte count after admission are re-lated to the 28-day mortality in patients with severe pneumonia and sepsis.The combined LAR,IL-6 level and CD4+T lympho-cyte count on the 3rd day can better assess the severity and prognosis of patients.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

Objective:To investigate the pathogenic genes, clinical features and treatment as well as follow-up of children with congenital long QT syndrome (LQTS).Methods:The clinical data, genetic test results and follow-up data of 16 congenital LQTS children with syncope as the first manifestation admitted to the Department of Cardiology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to March 2023 were collected and retrospectively analyzed.Results:Among the 16 LQTS patients, the age of first syncope onset was 1.3-13.3 (7.37±3.41) years, and the interval between first syncope onset and clinical diagnosis was 0-48 (14.8±16.2) months.A total of 13 (81.3%) patients had triggers of syncope, of which nine were exercise-induced and four were emotional induced.Genetic testing was performed in 13 patients with LQTS, of which 12 (92.3%) were found to have pathogenic or suspected pathogenic mutations from KCNQ1, KCNH2, and SCN5A gene.The corrected QT interval of 16 patients was (550.0±50.2) ms, all cases≥460 ms.Schwartz scored 6.0 (5.0, 6.0) points, all cases≥4 points.All patients were initially treated with metoprolol or propranolol, of which 14 patients were followed up to date, three patients had recurrent syncope, and five patients stopped taking the medicines by themselves.One patient with high-dose metoprolol (LQT2) was treated with mexiletine after recurrent episodes.One patient who was intolerant to high-dose propranolol underwent left cardiac sympathectomy and was followed up after surgery without syncope episodes.None of the patients underwent implantable cardioverter defibrillator implantation. Conclusion:Children with LQTS and syncope symptoms have high positive rate of genetic tests.The genetic results could assist typing of patients with LQTS and guide treatment.Routine electrocardiogram screening in children with syncope may diagnose LQTS earlier and reduce misdiagnosis and missed diagnosis.β-blockers are the cornerstone of treatment for patients with LQTS.Strengthening follow-up management and improving patients′ treatment compliance is conducive to further improving the treatment response rate of patients.

Objective:To analyze the clinical features and follow-up of children with cardiogenic syncope (CS), and accurately and efficiently guide clinical diagnosis as well as improve the prognosis of children with CS.Methods:Ninety-eight children with CS who were hospitalized in the Department of Cardiology, Beijing Children′s Hospital Affiliated to Capital Medical University from April 1, 2016 to June 31, 2023 were selected as the study objects.According to the etiology type, the children with CS were divided into arrhythmia group, organic cardiovascular disease group and mixed group.The causes of syncope episodes, type of aura, frequency of syncope at first diagnosis, duration of loss of consciousness, concomitant symptoms, past history, family history, physical examination and follow-up were collected and statistically analyzed in each group.Results:A total of 98 children with CS were included, including 59 males and 39 females.The age of first onset was (8.69±3.90) years old.There were 60 cases in arrhythmia group, 18 cases in organic cardiovascular disease group and 20 cases in mixed group.There were no statistically significant differences among three groups of children in whether had inducement, whether had aura, incidence of aura types, duration of loss of consciousness, incidence of urinary and fecal incontinence and associated symptoms of fall injury, incidence of liver macrosis, and recurrence of syncope during follow-up.The children in arrhythmia group were more likely to induce syncope due to intense exercise than those in mixed group ( χ2=9.785, P<0.05). Compared with the organic cardiovascular disease group and the mixed group, the number of syncope attacks in the arrhythmia group was more than five times at the first diagnosis ( P=0.020). Compared with the organic cardiovascular disease group, the children in mixed group and arrhythmia group were more likely to have accompanying symptoms during syncope( P<0.05), and the incidences of convulsion were the higher in both groups.The positive signs of heart in mixed group were more than those in arrhythmia group and organic cardiovascular disease group( P<0.05). Compared with arrhythmia group, facial cyanosis was more common in mixed group and organic cardiovascular disease group ( P<0.05). Of the 87 children with CS who were followed up regularly, 73 (83.9%) did not have recurrent syncope after timely treatment and regular outpatient medication adjustment. Conclusion:Children with CS have special clinical characteristics, such as syncope is easily induced by strenuous exercise or emotional excitement, syncope is often preceded by no aura of seizure, loss of consciousness lasts for a relatively short period of time, the main accompanying symptom of syncope is convulsions, positive cardiac signs can be seen on physical examination, and there can be cardiac disorders in the past history or sudden death in the family history.It is of great significance to improve the diagnosis and prognosis of children with CS by mastering its characteristics and giving timely and appropriate treatment.

Objective:To investigate the short-term efficacy of left-sided three-port total laparoscopic distal gastrectomy (TPTLDG).Methods:The prospective randomized controlled study was conducted. The 68 patients undergoing laparoscopic distal gastrectomy in the First Affiliated Hospital of Air Force Medical University from March 2022 to March 2023 were collected. All patients were randomly assigned to the TPTLDG group with a double number, and to the five-port laparoscopic distal gastrectomy (FPLDG) group with a single number, respectively. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of perioperative condition; (3) comparison of complications during postoperative 30 days; (4) comparison of pathological examination. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or continuous correction chi-square test. Comparison of ordinal data was analyzed using the non‐parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 59 patients of gastric cancer were selected for eligibility. There were 40 males and 19 females, aged 59.00(52.00, 67.00)years. The gender (male, female), age, body mass index (BMI), Caprini score (≤2, ≥3), nutritional risk screening 2002 (<3, ≥3), Eastern Coopera-tive Oncology Group performance status (0, 1), preoperative hypersensitive C-reactive protein, preoperative IL-6, preoperative white blood cell count, preoperative albumin were 19, 11, 59.00(51.25,65.25)years, 21.92(20.93,22.73)kg/m 2, 7, 23, 24, 6, 18, 12, 0.78(0.78,1.46)mg/L, 3.07(1.50,10.56)μg/L, 6.07(4.94,7.19)×10 9/L, 44.30(40.83, 46.15) g/L in the 30 patients of TPTLDG group, versus 21, 8, 57.00(51.00, 67.00)years, 21.90(20.95, 23.35)kg/m 2, 11, 18, 24, 5, 17, 12, 1.13(0.78,11.40)mg/L, 5.56(1.88,15.12)μg/L, 5.54(4.71,6.70)×10 9/L, 43.55(40.25,44.88)g/L in the 29 patients of FPLDG group, showing no significant difference in the above indicators between the two groups ( χ2=0.557, Z=-0.444, -0.805, χ2=1.482, 0.074, 0.012, Z=-1.259, -1.262, -0.819, -1.199, P>0.05), confounding bias ensured comparability between the two groups. (2) Comparison of perioperative condition. The length of incision, time to removing drainage tube, IL-6 at postoperative day 3, cost of hospital stay were 6.65(6.48,6.93)cm, 3.00(0,3.00)days, 29.18 (13.67, 43.53)μg/L, 84 164.15(73 084.72, 96 782.14)yuan in the TPTLDG group, versus 8.00(7.50,8.35)cm, 3.00(3.00,4.00)days, 47.56(21.31,85.79)μg/L, 92 120.43(87 069.33, 113 089.74)yuan in the FPLDG group, showing significant differences in the above indicators between the two groups ( Z=-11.065, -2.141, -2.940, -2.220, P<0.05). (3) Comparison of complications during postoperative 30 days. The incidence rate of complications during postoperative 30 days was 30.00%(9/30) and 24.14%(7/29) in the TPTLDG group and FPLDG group, respectively, showing no significant difference between the two groups ( χ2=0.256, P>0.05). (4) Comparison of pathological examination. Cases with pathological N staging as 0 stage, 1 stage, 2 stage, 3 stage were 22, 2, 4, 2 in the TPTLDG group, versus 13, 7, 4, 5 in the FPLDG group, showing a significant difference between the two groups ( Z=-2.021, P<0.05). Conclusion:TPTLDG is safe and feasible for gastric cancer, with a good short-term efficacy.

Myostatin (Mstn) is known as growth/differentiation factor-8 (GDF-8). Knockout or knockdown of Mstn gene promotes muscle development and reduces fat content. Here we prepared Mstn knockdown mice by RNA interference, then the morphology of the skeletal muscle, the content of triglyceride (TG), the content and composition of fatty acids in the skeletal muscle were detected. The expression of Mstn reduced in muscle of Mstn knockdown mice compared to the controls. The cross sectional areas of the skeletal muscle myofibers were significantly larger while the content of TG was less than that of the controls, and the ratios of n-3/n-6 and unsat/sat in the knockdown mice increased significantly. Subsequently, we detected the expression of genes associated with fatty acid metabolism. The expression of the genes associated with lipolysis and fatty acid transportation were up-regulated, while the genes associated with fatty acid synthesis were down-regulated. Of these genes, the up-regulation of a gene associated with β oxidation, Cpt1b, was up-regulated remarkably. We further detected the enzyme activity of CPT1 in skeletal muscle and obtained the same results with gene expression. Moreover, chromatin immunoprecipitation assay was performed and we found that SMAD3, a transcription factor downstream of Mstn, directly binds to the promoter of Cpt1b gene. These results showed that knockdown of Mstn up-regulated the expression of Cpt1b through the binding of SMAD3 to the promoter of Cpt1b, then promoted the β oxidation metabolism of intramuscular fatty acids.
Animals ; Carnitine O-Palmitoyltransferase/metabolism* ; Fatty Acids ; Lipid Metabolism ; Mice ; Mice, Knockout ; Muscle, Skeletal/metabolism* ; Myostatin/metabolism* ; Oxidation-Reduction ; Up-Regulation