Objective To investigate the association between four single nucleotide polymorphisms(SNP)(rs9340 in MAPK1,rs14804 in NRAS,rs712 and rs7973450 in KRAS)in the 3'UTR of ERK1/2 signaling pathway-related genes and non-small cell lung cancer(NSCLC).Methods A total of 478 NSCLC patients and 480 healthy controls were enrolled in this study.Four SNPs were genotyped by using TaqMan assays.The association between the four SNPs and NSCLC was analyzed.Results The distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the non-small cell squamous cell carcinoma(SCC)group(P = 0.009),suggesting that the G allele of rs9340 may be a protective factor for non-small cell lung squamous cell carcinoma(OR = 0.67,95%CI:0.50～0.91).In addition,in the<50 years age group,the distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the NSCLC group(P = 5.07×10-4),indicating that the G allele of rs9340 may be a protective factor for NSCLC(OR = 0.46,95%CI:0.29～0.72).Conclusion The SNP rs9340 in MAPK1 may be associated with the risk of NSCLC.

Objective To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma(HCC)microenvironment and its impact on proliferation and stemness of HCC cells.Methods TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC.Specific expression patterns of UBE2S,intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website.We further examined UBE2S expressions in clinical samples of HCC tissues,HCC cells and T cells using immunohistochemistry and immunofluorescence staining.We also tested the effects of UBE2S knockdown on stemness of HCC-LM3 and HepG2 cells using clone formation experiments and sphere formation assay.Results Analysis based on TCGA database suggested significant overexpression of UBE2S in both paired and non-paired tumor tissues(P<0.001),and its transcriptional level increased with tumor grades.The methylation level of UBE2S promoter was significantly decreased in HCC(P<0.001),and its transcription level increased obviously in HCC with TP53 mutation(P<0.001).Analysis of CPTAC database also demonstrated overexpression of UBE2S protein in HCC tissues(P<0.001).Three prognostic models suggested that HCC patients with high UBE2S expression had poorer prognosis(P<0.001).Single-cell sequencing data analysis revealed high expressions of UBE2S in T cells and high intensities of interaction between endothelial cells,epithelial cells and fibroblasts in HCC microenvironment.Immunohistochemistry and immunofluorescence staining demonstrated high UBE2S expressions in clinical samples of HCC tissues,HCC cells and T cells.In HCC-LM3 and HepG2 cells,UBE2S knockdown significantly inhibited cell clone formation and tumor sphere formation(P<0.05).Conclusion UBE2S is highly expressed in T cells in HCC microenvironment in close correlation with a poor prognosis.High UBE2S expression promotes the stemness of HCC cells.

Objective To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma(HCC)microenvironment and its impact on proliferation and stemness of HCC cells.Methods TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC.Specific expression patterns of UBE2S,intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website.We further examined UBE2S expressions in clinical samples of HCC tissues,HCC cells and T cells using immunohistochemistry and immunofluorescence staining.We also tested the effects of UBE2S knockdown on stemness of HCC-LM3 and HepG2 cells using clone formation experiments and sphere formation assay.Results Analysis based on TCGA database suggested significant overexpression of UBE2S in both paired and non-paired tumor tissues(P<0.001),and its transcriptional level increased with tumor grades.The methylation level of UBE2S promoter was significantly decreased in HCC(P<0.001),and its transcription level increased obviously in HCC with TP53 mutation(P<0.001).Analysis of CPTAC database also demonstrated overexpression of UBE2S protein in HCC tissues(P<0.001).Three prognostic models suggested that HCC patients with high UBE2S expression had poorer prognosis(P<0.001).Single-cell sequencing data analysis revealed high expressions of UBE2S in T cells and high intensities of interaction between endothelial cells,epithelial cells and fibroblasts in HCC microenvironment.Immunohistochemistry and immunofluorescence staining demonstrated high UBE2S expressions in clinical samples of HCC tissues,HCC cells and T cells.In HCC-LM3 and HepG2 cells,UBE2S knockdown significantly inhibited cell clone formation and tumor sphere formation(P<0.05).Conclusion UBE2S is highly expressed in T cells in HCC microenvironment in close correlation with a poor prognosis.High UBE2S expression promotes the stemness of HCC cells.

The anterior disc displacement (ADD) leads to temporomandibular joint osteoarthritis (TMJOA) and mandibular growth retardation in adolescents. To investigate the potential functional role of fibrocartilage stem cells (FCSCs) during the process, a surgical ADD-TMJOA mouse model was established. From 1 week after model generation, ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis (OA)-like joint cartilage degeneration, manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis. Lineage tracing using Gli1-CreER⁺; Tm^fl/-mice and Sox9-CreER⁺;Tm^fl/-mice showed that ADD interfered with the chondrogenic capacity of Gli1⁺ FCSCs as well as osteogenic differentiation of Sox9⁺ lineage, mainly in the middle zone of TMJ cartilage. Then, a surgically induced disc reposition (DR) mouse model was generated. The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice. And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment. In conclusion, ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage, resulting in cartilage degeneration and loss of subchondral bone homeostasis, finally causing TMJ growth retardation. DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.
Animals ; Mice ; Osteogenesis ; Zinc Finger Protein GLI1 ; Fibrocartilage ; Temporomandibular Joint ; Disease Models, Animal ; Osteoarthritis ; Stem Cells ; Growth Disorders

Objective:To evaluate the 2-dimension and 3-dimension changes of upper airway of patients who were diagnosed with idiopathic condylar resorption (ICR) and anterior open bite as well as received bilateral temporomandibular joint (TMJ) prostheses replacement or bimaxillary orthognathic surgery.Methods:This study is a retrospective study. Seventeen patients diagnosed as ICR and anterior open bite in Department of Orthognathic and TMJ surgery, West China Hospital of Sichuan University were selected (January 2018 to December 2021) and divided into bilateral TMJ protheses replacement group (group R, n=8) and orthognathic group (group O, n=9), according to which surgery they have performed. In order to compare variation of upper airway before and after surgery in different dimensions and sections within the same group or between groups, Spiral computed tomography data were obtained before (1 month) and after operation (10 to 12 months) to measure the total volume of airway (VT), the maximum sagittal area (MSA), the maximum cross-sectional area (MACA), the minimum cross-sectional area (MICA), the area of the most posterior plane(PPA), the area of soft-palate plane (SPA), the area of the most posterior point of tongue base plane (PTA), the area of the root of epiglottis plane (EA), the oropharyngeal airway volume (VO), the glossopharyngeal airway volume (VG) and the laryngeal airway volume (VL). Wilcoxon signed-rank test were used to complete statistical analyses for VO (T2),SPA (T2),ΔMSA,ΔMACA in group R as well as PTA (T1),EA (T2) in group O. Statistical analyses of other items were performed with student′s t test. Results:VT, VO, VG, VL, MSA, MACA, MIC, PPA, PTA and EA of group R (T2) were significantly increased after TMJ prosthesis with Lefort Ⅰ osteotomy ( P<0.05). Meanwhile the VT, VO, VG, MSA, MACA, MICA, PPA and SPA of group O (T2) were significantly increased ( P<0.05). There were significant difference in ΔVT and ΔVL between group R [(6 854.80±3 197.82) mm 3, (2 252.85±1 527.96) mm 3] and group O [(3 367.91±3 124.62) mm 3, (413.21±1 244.44) mm 3]( t=2.27, P=0.038; t=2.74, P=0.015). Conclusions:Bilateral temporomandibular joint (TMJ) prostheses replacement and bimaxillary orthognathic surgery can both enlarge the areas and volumes of upper airway in patients who suffer from ICR and anterior open bite. Compared with bimaxillary orthognathic surgery, bilateral temporomandibular joint prostheses replacement plays a more pronounced role in enlargement and reconstruction of middle-inferior section of upper airway.

Target identification of bioactive compounds is important for understanding their mechanisms of action and provides critical insights into their therapeutic utility. While it remains a challenge, unbiased chemoproteomics strategy using clickable photoaffinity probes is a useful and validated approach for target identification. One major limitation of this approach is the efficient synthesis of appropriately substituted clickable photoaffinity probes. Herein, we describe an efficient and consistent method to prepare such probes. We further employed this method to prepare a highly stereo-congested probe based on naturally occurring triterpenoid betulinic acid. With this photoaffinity probe, we identified tropomyosin as a novel target for betulinic acid that can account for the unique biological phenotype on cellular cytoskeleton induced by betulinic acid.

Since the founding of the People′s Republic of China in 1949, China′s vaccination work has been making remarkable achievements. However, under the state of emergency, such as major infectious disease outbreaks, major natural disasters, vaccine-related events, large-scale population entry at the border, vaccination services confront many challenges, and the emergency plan for vaccination services in most areas is still in the exploratory stage. Based on the experience at home and abroad, combined with China′s relevant policies, technical guidelines and evidence, this study provides suggestions for vaccination services in aforementioned emergency events, in order to standardize the development and implementation of vaccination services under the state of emergency in China.

Since the founding of the People′s Republic of China in 1949, China′s vaccination work has been making remarkable achievements. However, under the state of emergency, such as major infectious disease outbreaks, major natural disasters, vaccine-related events, large-scale population entry at the border, vaccination services confront many challenges, and the emergency plan for vaccination services in most areas is still in the exploratory stage. Based on the experience at home and abroad, combined with China′s relevant policies, technical guidelines and evidence, this study provides suggestions for vaccination services in aforementioned emergency events, in order to standardize the development and implementation of vaccination services under the state of emergency in China.

Objective:To study the feasibility and safety in treatment of trauma to right posterior liver using laparoscopic surgery with patients in the left semiprone position.Methods:The clinical data of consecutive patients who were diagnosed to have trauma to the right posterior liver and were treated with laparoscopic surgery with patients in the left semiprone position at the Department of Hepatobiliary Surgery, the Affiliated Hospital of Youjiang Medical University for Nationalities between February 2016 and August 2020 were retrospectively analysed. The patients’ gender, age, mechanisms of injury, operative methods, operative time, amounts of abdominal effusion, degrees of liver injury, extents of intraoperative bleeding, amounts of postoperative drainage, lengths of postoperative hospital stay, and major postoperative complications were recorded and analyzed.Results:Among the 18 patients, there were 16 males and 2 females, aged (41.6±14.4) years. The mechanisms of liver trauma were caused by fall injury ( n=10), traffic accidents ( n=4), blunt injury ( n=2) and penetrating injury ( n=2). The levels of injuries were level Ⅲ in 16 patients and level Ⅳ in 2 patients. Laparoscopic suture repair was performed in 8 patients, partial hepatectomy in 4 patients, electrocoagulation hemostasis in 4 patients and ligation of bleeding vessels in 2 patients. All were successful in hemostasis. Abdominal effusion was (1 528.8±373.2) ml, intraoperative blood loss (80.6±16.7) ml, operation time (88.5±9.1) min, postoperative hospital stay 7 days and postoperative total drainage (93.8±13.6) ml. Ten patients were complicated with right pleural effusion, and they recovered with conservative treatment. There were no bile leakage, infection and other complications. Conclusion:Trauma to right posterior liver treated with laparoscopic with surgery patients in the left semiprone position had the advantages of adequate exposure which facilitated surgical hemostasis, resulting in minimal collateral damages and short hospital stay. The treatment was feasibility and safe.

Objective:To explore the value of three-dimensional speckle tracking imaging (3D-STI) and conventional echocardiography in evaluating left ventricular function characteristics of sarcomere mutation carriers in hypertrophic cardiomyopathy.Methods:Totally 91 subjects with sarcomere mutations in family HCM but without left ventricular hypertrophy (G + /P - group), and 100 normal family members with gender and age matched as the control group (G -/P - group) were enrolled from the center of hypertrophic cardiomyopathy of Xijing Hospital affiliated to the Air Force Military Medical University from February 2013 to April 2017. They all received the comprehensive evaluation of 3D-STI and conventional echocardiography. The ultrasonic paramaters between the two groups were compared. And the diagnostic performance of these paramaters with sarcomere mutations was evaluated. Results:Compared with the G -/P - group, the G + /P -group had larger left atrial diameter (LAD), longer left ventricular isovolumic relaxation time (IVRT), reduced mitral annular systolic velocity (e′), elevated E/e′ ratio, as well as impaired left ventricular global longitudinal and radial strain(GLS and GRS) ( P<0.05). Moreover, the GLS≤19.9%(AUC 0.861, sensitivity 61.4%, specificity 98.5%) and IVRT≥75.5 ms(AUC 0.762, sensitivity 61.4%, specificity 72.6%) showed the best diagnostic performance with sarcomere mutations ( P<0.05). Conclusions:In HCM family members, the sarcomere mutations carriers without left ventricular hypertrophy exhibit impaired left ventricular diastolic function, reduced longitudinal and radial systolic function.Moreover, the GLS and IVRT show the best diagnostic performance for those with sarcomere mutations.