Objective:To explore the clinical and genetic etiology of a Chinese pedigree affected with type 2 Long QT syndrome (LQTS).Methods:A pedigree with type 2 LQTS presented at Fuwai Central China Cardiovascular Hospital on August 23, 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out for the proband, and candidate variant was screened through functional annotation and protein-protein interaction (PPI) analysis. Sanger sequencing was conducted to verify the pathogenicity of candidate variant. This study was approved by Medical Ethics Committee of the Fuwai Central China Cardiovascular Hospital (Ethics No. 2019-15).Results:WES revealed that the proband has harbored a missense variant of the KCNH2 gene, namely c. 1478A>G (p.Tyr493Cys), which was confirmed by Sanger sequencing to have inherited from her father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_supporting+ PM5+ PP3+ PP4). Conclusion:The KCNH2 gene c. 1478A>G (p.Tyr493Cys) variant probably underlay the type 2 LQTS in this pedigree.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective:To explore the factors affecting changes of disc angle (ΔDA) during oblique lateral interbody fusion (OLIF) and establish a predictive model of ΔDA.Methods:This retrospective study included 119 patients with 174 segments undergoing OLIF procedures between July 2017 and August 2019 in Beijing Jishuitan Hospital. 45 males and 74 females with an average age of 62.1±9.8 years (33-86 years) were included. The lordotic cages were all 6 degrees. Radiographic parameters included preoperative and postoperative disc angle (DA), disc height (DH), ΔDA on flexion-extension views (ΔDA-FE), cage location and cage inclination. Pearson correlation coefficient and machine-learning techniques were utilized to identify factors related to ΔDA. Based on machine leaning techniques, ten-fold cross-validation for model training and validation were used to develop a predictive linear model for ΔDA.Results:The average ΔDA was 3.9°±4.8° with preoperative disc angle (preoperative DA) of 5.3°±5.0°. The average change of posterior DH (ΔPDH) was 3.1±2.1 mm with preoperative posterior DH of 6.6±1.9 mm. The average change of anterior DH was 6.1±3.2 mm. Pearson correlation analysis showed a significant negative correlation between ΔDA and preoperative DA ( r=-0.713, P<0.001), cage location ( r=-0.183, P=0.016), and ΔDA-FE ( r=-0.153, P=0.044). PDH changes were significantly negatively correlated with preoperative PDH ( r=-0.444, P<0.001) and positively correlated with cage location ( r=0.218, P=0.004). ΔDA was 10.8°±3.2° for negative preoperative DA (indicating kyphotic), 5.0°±3.7° for preoperative DA between 0° and 6°, and 1.0°±4.1° for preoperative DA>6°. A predictive model was developed using ten-fold cross-validation, resulting in the formula ΔDA=7.9°-0.8×preoperative DA ( R=0.707, MAE=2.837). Conclusion:Disc angle changes in OLIF primarily depend on the preoperative disc angle, secondly on cage location. The predicting model based on machine-learning techniques using preoperative disc angle facilitates preoperative planning for OLIF procedures.

AIM:To evaluate the effectiveness of heparin-binding protein(HBP)in combination with organ function indicators for early diagnosis and prognosis prediction in patients with severe trauma complicated with sepsis.METHODS:A retrospective analysis was conducted on 184 patients with multiple injuries who were admitted to the Emergency Medicine Department of the Second Affiliated Hospital of Zhejiang University Medical College between January 2019 and September 2020 and underwent HBP testing.Patients were classified according to the SEPSIS 3.0 diagnostic cri-teria into a sepsis group(n=89)and a non-sepsis group(n=95).Clinical outcomes were tracked,dividing patients into a deceased group(n=43)and a survival group(n=141).HBP levels were continuously measured,and the peak values of the two groups were compared to assess the efficacy of diagnosing sepsis.Further analysis on the correlation of HBP peak value median with clinical prognosis was conducted.The effectiveness of HBP alone and in combination with total biliru-bin(TBil)and white blood cell(WBC)count in prognosis assessment was evaluated.RESULTS:(1)No significant dif-ference was found in the peak level of HBP between the sepsis group(n=89)and the non-sepsis group(n=95)(71.7±68.6 vs 52.5±56.1,P=0.051).(2)Among the 184 patients,the peak level of HBP was positively correlated with WBC count(r=0.244,P<0.01)and TBil levels(r=0.241,P<0.01).(3)The area under curve(AUC)for independent diag-nosis of sepsis using TBil levels,WBC count,and PCT levels were 0.618,0.631,and 0.718,respectively,and the com-bined AUC was 0.684,with a diagnostic sensitivity of 60.7%and specificity of 71.6%(P<0.05).(4)Prognostic analy-sis of mortality showed that patients in the high HBP level group had a significantly higher mortality rate than those in the low-level group(30.4%vs 16.3%,P<0.05).The WBC count was also significantly higher in the deceased group than in the survival group(17.5±6.9 vs 12.8±4.7,P<0.01),especially in those with sepsis(P<0.01).The AUCs for predict-ing sepsis mortality prognosis using HBP peak level,TBil levels,WBC count,SOFA score,and APACHE-II score were 0.618,0.603,0.719,0.823,and 0.811,respectively.The combined AUC of HBP with TBil and WBC for assessing sepsis prognosis was 0.750,with a sensitivity of 74.4%and specificity of 74.5%,showing statistically significant differ-ences(P<0.05).(5)The combined assessment of these three indicators showed no statistically significant difference from artificial scoring systems in predicting sepsis prognosis(P>0.05).CONCLUSION:The combination of HBP,TBil,and WBC is highly effective in predicting the risk of sepsis in patients with multiple injuries and has significant clinical value in predicting the mortality risk of trauma patients with sepsis.

Diabetes mellitus(DM)stands as a chronic metabolic ailment predominantly characterized by elevated blood glucose lev-els,stemming from either a resistance to insulin or aberrations in insulin secretion.The ensuing persistent hyperglycemia,a direct con-sequence of pancreatic β-cell devastation,acts as a catalyst for a myriad of complications,inclusive of extensive neuropathies.The dis-ease has substantial prevalence and mortality rates,underscoring the gravity of its impact on public health.Dental pulp stem cells(DPSCs)are readily obtainable,and they exhibit a profound capacity for self-renewal,multi-lineage differentiation,and vigorous pro-liferation.Remarkably,DPSCs can differentiate into pancreatic β-cells,subsequently participate in insulin secretion and play a pivotal role in immune modulation.This has achieved notable advancements in the therapeutic domain,particularly in the treatment of chronic diseases.Furthermore,DPSCs harbor the potential to mitigate symptoms in patients afflicted with type 1 diabetes.They navigate this therapeutic pathway through mechanisms that involve suppressing autoimmunity,modulating inflammatory responses,and counteracting oxidative stress.This article meticulously reviews the biological characteristics inherent to DPSCs and explores their multifaceted thera-peutic potential in addressing DM and its associated complications.Through this endeavor,the article aims to contribute to the refine-ment and enhancement of DM management strategies.

Taking into consideration the characteristics and current development status of air medical rescue,an analysis is conducted from the perspective of hospitals to examine the focal points and challenges in establishing the capability of hospital air medical rescue.A capability framework comprising five modules,namely planning system,service model,professional teams,hardware platform,and operational procedures,is proposed.The key tasks for each module are sorted out.Furthermore,the ex-ploration and practical experience of The First Affiliated Hospital of Sun Yat-sen University are shared,with the aim of providing a reference for the construction of hospital air medical rescue capabilities in the modern era.

Objective To compare the clinical outcomes between oblique lumbar interbody fusion(OLIF)and transforaminal lumbar interbody fusion(TLIF)for patients with degenerative spondylolisthesis during 2-year follow-ups.Methods Patients with symptomatic degenerative spondylolisthesis who underwent OLIF(46 cases)and TLIF(45 cases)between July 2017 and September 2020 with 2-year follow-ups were retrospectively reviewed.One level or two-level lumbar fusion were included.The primary outcomes were Visual Analogue Scale(VAS)and Oswestry Disability Index(ODI)at 2 years after surgery.The secondary outcomes included radiographic parameters,fusion rate,cage subsidence rate,and permanent nerve injury rate.Results No significantly different changes were noted in VAS-back[2(2,3)vs.2(2,2),P=0.943],VAS-leg[2(2,2)vs.2(2,2),P=0.988],and ODI[17％(10％,22％)vs.14％(10％,22％),P=0.417]between the OLIF group and the TLIF group,respectively.Greater restoration of disc height and segmental lordosis were obtained in the OLIF group[mean,(11.9±1.5)mm and 15.7°±7.2°]than in the TLIF group[mean,(9.2±2.0)mm and 12.5°±5.9°]at postoperative 2-year(P＜0.001 and P=0.029).The subsidence rate was lower in the OLIF group than in the TLIF group[19.6％(9/46)vs.40.0％(16/40),P=0.037].The fusion rates at postoperative 2-year were 93.5％(43/46)in the OLIF group and 87.5％(35/40)in the TLIF group,having no significant difference(P=0.562).The rates of permanent nerve injury were similar between the two groups[4.3％(2/46)vs.6.7％(3/45),P=0.980]at postoperative 2-year.Conclusion Short segment OLIF doesn't show better clinical outcomes and fusion rate than TLIF for degenerative spondylolisthesis,except for greater disc height restoration,greater segmental lordosis,and lower subsidence rate at postoperative 2-year.

Objective:To observe any effect of high-intensity exercise on cardiac remodeling and nitroso-redox imbalance in rats modeling type 1 diabetes so as to provide a theoretical basis and targets for prescribing rehabilitation exercise for patients with diabetic cardiomyopathy.Methods:Forty-five 8-week-old healthy, male Sprague-Dawley rats were randomly divided into a normal control group (NC) of 10, a diabetic control group (DMC) and a diabetic exercise group (DME). Type 1 diabetes was induced in the DMC and DME groups by injecting streptozotocin. The NC and DMC group rats were then fed quietly in their cages, while the DME group rats performed high-intensity treadmill exercise 5 times a week for 4 weeks. Forty-eight hours after the last training, cardiac structure and function were detected by echocardiography, and fasting blood glucose was measured by the glucose oxidase method. Cardiomyocyte cross-sectional area (CSA) and interstitial collagen volume fraction (CVF) were observed. Myocardial tetrahydrobiopterin (BH4) content was determined chromatographically, and myocardial p47 phox and p67 phox protein, endothelial nitric oxide synthase (eNOS), and eNOS dimer and monomer protein levels were detected using western blotting. Results:Compared with the NC group, the average blood glucose, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), myocardial CSA and CVF, and p47 phox and p67 phox protein expression had all increased significantly, but the eNOS dimer/monomer ratio and BH4 content had decreased significantly in the DMC group. In the DME group the average blood glucose, LVEDD, LVESD, myocardial CSA and CVF were significantly lower than in the DMC group, while there was no significant difference between the two groups in p47 phox or p67 phox protein expression, the eNOS dimer/monomer ratio or BH4 content. Conclusion:Short-term, high-intensity exercise can inhibit cardiac remodeling in rats with diabetic cardiomyopathy, but it does not relieve the nitro-redox imbalance.

Objective: To explore the relationship between mobile phone dependence (MPD) and academic burden among junior middle school students in Guizhou Province, under the "double reduction" policy by using a multi level model, so as to provide a basis for preventing the occurrence of MPD. Methods: From December 2021 to January 2022, 7 868 students from grade 1 to grade 3 in 3 cities (prefecture) of Guizhou Province were selected by multi stage stratification random sampling method, and on site investigation was conducted by self compiled questionnaire and Self rating Questionnaire for Adolescent Problematic Mobile Phone Use(SQAPMPU). Using MLwiN 2.30 to fit a multi level model of the relationship between MPD and academic burden among junior middle school students. Results: The MPD detection rate of junior middle school students in Guizhou Province was 20.9%. The multi level model revealed that MPD of junior middle school students was clustered at the level of school and class ( χ 2= 1 565.32 , P <0.01), and high perceived academic pressure had a positive predictive effect on MPD among junior middle school students ( β =1.96). Homework duration ≥90 min/d at weekends had a negative predictive effect on MPD ( β =-0.55), while participation in off campus training on learning days had a positive predictive effect ( β =1.66)( P <0.05). Conclusion The MPD occurrence level is higher among junior middle school students in Guizhou Province. Perceived academic pressure, time spent on homework during weekends, off campus training and other academic burdens have an impact on MPD among junior middle school students, which should be a cause of concern for schools, families and social departments.