This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

Objective:To analyze the hard tissue thickness in the crown of primary teeth by CBCT.Methods:The CBCT imaging data of 47 children were included,and the hard tissue thickness of primary teeth was measured by MIMICS software.SPSS 22.0 was used for data analysis.Results:The average thickness in the mesial surfaces was the smallest(P＜0.01),except for the libial surface of maxillary central incisor and the distal surface of mandibular first primary molar.In primary anteriors,the thickness in the same sur-face of maxillary teeth was greater than that of mandibular teeth significantly(P＜0.01)except for the libial surface of primary canine.In primary molars,the thickness of hard tissue in the same part of the distal and lingual side of the maxillary teeth was greater than that of the mandibular teeth(P＜0.01),and the thickness in the buccal side of maxillary teeth was lower than that of the mandibular teeth(P＜0.01).Conclusion:The distribution of hard tissue thickness of primary teeth in different position is different.

Objective:To establish a nomogram for preoperative differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) based on clinical, ultrasound, and contrast-enhanced ultrasound (CEUS) data.Methods:A retrospective analysis was conducted on ultrasound and CEUS data of 462 patients who underwent hepatectomy in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to December 2023, including 262 cases of HCC (56.7%) and 200 cases of ICC (43.3%). The data were randomly divided into training set ( n=324) and validation set ( n=138) in a 7∶3 ratio. Univariate analysis was used to initially screen for variables with statistically significant differences between HCC and ICC groups in the training set, and LASSO regression was performed to select the variables with higher coefficients. Logistic regression analyses were then used to predict independent risk factors for ICC. A nomogram was drawn using R software. The performance of the nomogram was then validated using ROC curve, calibration curve, and decision curve analysis (DCA). Results:Univariate analysis showed that there were significant differences in age, gender, liver cirrhosis, HBsAg (+ ), ALP >185 U/L, CA19-9 >27 kU/L, CA242>10 kU/L, irregular shape, border, cholangiectasis, portal vein tumor thrombus, enhanced pattern in arterial phase, clearance time <60 s, intra-tumoral vein between ICC and HCC groups (all P<0.05). The top 10 features were selected for LASSO regression analysis. Logistic regression analysis revealed that gender, cirrhosis, CA19-9>27 kU/L, CA242>10 kU/L, cholangiectasis, clearance time <60 s, intra-tumoral vein and enhanced pattern in arterial phase were risk factors for ICC (all P<0.05). The area under the ROC curve in the training and validation groups were 0.963 and 0.914, respectively. In the training group, the specificity and sensitivity of the nomogram were 0.926 and 0.917, respectively, and in the validation group, they were 0.875 and 0.871, respectively. The calibration curve showed that the prediction effect of the model was in good agreement with the actual situation. DCA showed that the nomogram could increase the net benefit to the different diagnosis of ICC in patients. Conclusions:The nomogram based on clinical, ultrasound and CEUS features has a good predictive value for preoperative identification of ICC and provides reliable evidence for clinical practice.

Objective:To investigate the predictive value of the ratio of tricuspid annulus plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) in the progression of heart failure with reduced ejection fraction (HFrEF) patients.Methods:A total of 172 patients with HFrEF in the First Affiliated Hospital of Zhengzhou University from January to December 2022 were prospectively selected. All participants underwent routine echocardiography, the routine cardiac ultrasound parameters, left atrial volume index (LAVi), right ventricular fractional area change (RVFAC) were measured. The ratio of early diastolic velocity E peak of the mitral valve orifice to the early diastolic mean velocity e′ of the mitral valve annulus (E/e′) and TAPSE/PASP were calculated. The online quantitative analysis software of the ultrasound instrument were used to obtain the left ventricular global longitudinal strain (LVGLS), left atrial reservior strain (LASr), left atrial conduit strain (LAScd), left atrial contraction strain (LASct), right ventricular global systolic strain (RVGLS), and right ventricular free wall strain (RVFWS). According to the median of TAPSE/PASP, the patients were divided into TAPSE/PASP≥0.50 mm/mmHg group(group 1, 85 cases) and TAPSE/PASP<0.50 mm/mmHg group(group 2, 87 cases). The endpoint events were recorded. The differences of the above parameters in two groups were compared, the correlation analysis was used to analyze the correlations between myocardial mechanical parameters and TAPSE/PASP. The Kaplan-Merier method was used to draw survival curves, and the Log-rank method was used to compare the differences in survival curves in the two groups. The univariate and multivariate Cox regression models were used to analyze the predictive value of TAPSE/PASP for end-point events.Results:There were no significant differences in age, gender, body mass index, complications and left ventricular end-diastolic volume (LVEDV) between the two groups (all P>0.05). Compared with group 1, patients in group 2 showed a significant decrease in RVFAC and TAPSE (all P<0.05), while the LAVi, left ventricular end-systolic volume (LVESV), right ventricular end-diastolic diameter (RVDd-base), E/e′ and PASP were increased (all P<0.05), the absolute values of LVGLS, LASr, LASct, RVGLS, and RVFWS were significantly decreased (all P<0.05). Correlation analysis showed that LVGLS, LASr, RVGLS, RVFAC and 6-min walking distance were linearly correlated with TAPSE/PASP ( r/ rs=-0.176, 0.181, -0.496, 0.472, 0.421; all P<0.05). The follow-up time was (11.71±1.80) months, and the incidence of death events in group 2 (28.73%) was higher than that in group 1 (10.61%), with a significant difference ( P<0.05). The results of multivariate Cox regression analysis showed that TAPAE/PASP was one of the independent predictive factors for endpoint events in HFrEF patients, with adjusted HR: 0.306, 95% CI=0.141-0.663, P=0.003. Conclusions:TAPSE/PASP can monitor the progression of chronic heart failure and is one of the independent predictive factors, providing a new reference indicator for clinical diagnosis and treatment.

Objective:To establish and evaluate a clinical and ultrasound parameters-based nomogram for the preoperative differentiating diagnosis of intrahepatic cholangiocarcinoma (ICC).Methods:A total of 723 patients undergoing hepatectomy in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2016 to August 2022 were retrospectively screened. A total of 399 patients with hepatocellular carcinoma (HCC, 198 cases) or ICC (201 cases) were enrolled in this study, including 284 males and 115 females, aged (60.5±10.5) years. Through random sampling using computer-generated random numbers, patients were divided into training ( n=279) and validation groups ( n=120) in a ratio of 7∶3. Univariate and multivariate logistic regression were performed to identify factors differentiating ICC, and a nomogram was established using R software based on independent risk factors for ICC. The accuracy of the nomogram was evaluated by receiver operating characteristic curve and calibration curves. Decision curve analysis was performed to assess the net benefit of the model. Results:Multivariate logistic regression analysis showed that irregular shape, cholangiectasis, female, cirrhosis, carbohydrate antigen 242 >10 U/ml, carbohydrate antigen 125 >30 U/ml and alpha-fetoprotein >10 μg/L were independent differentiating factors for ICC (all P<0.05). A nomogram was constructed based on those factors. The nomogram showed a better discrimination between ICC and HCC. The area under the curve of the training group and the validation group were 0.966 and 0.956, respectively. The calibration curve showed that the prediction effect of the model is in good agreement with the actual situation. Decision curve analysis showed that the nomogram was more effective than diagnosing all patients as either HCC or ICC, which yielded a net benefit at the most reasonable threshold probabilities. Conclusion:The nomogram for the preoperative diagnosis of ICC based on clinical and ultrasound features showed a good diagnostic performance.

Encephalomyocarditis virus (EMCV) is a non-enveloped, positive-sense, single-stranded RNA virus that belongs to the family Picornaviridae and the genus Cardiovirus. EMCV has the ability to infect various mammals, such as mice, pigs, and cattle. In addition, humans are susceptible to EMCV infection, and the seropositivity rate of relevant antibodies in healthy populations is steadily increasing, which poses a potential risk of epidemics. The initial step of viral infection in cells involves recognition and attachment to cell surface receptors, followed by endocytosis into the cells. Subsequently, viral proteins interact with host proteins within the cells to promote their own replication. With the progress made in protein-protein interaction studies and the development of high-throughput sequencing technologies, multiple host proteins that interact with EMCV have been identified. This article summarizes the host proteins that interact with EMCV during infection, explores the mechanisms by which these proteins facilitate or inhibit viral invasion, discusses the latest progress in EMCV-induced endocytosis and intracellular signaling, hoping to provide reference for better elucidating EMCV receptor proteins, understanding viral infection and replication mechanisms, studying virus-host interactions and tissue tropism, and developing novel targeted antiviral drugs and prevention strategies.

Objective To investigate the distribution characteristics of antibiotics in source water and their health risks to human body in Yichang City, and to provide a scientific basis for the prevention and control of new types of pollution such as antibiotics in drinking water. Methods Solid phase extraction (SPE) was used for enrichment, and ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to detect and analyze the content of five types of antibiotics including sulfonamides, tetracyclines, chloramphenicol, quinolones and β-lactams in the main drinking water sources of Yichang City. The human health risk assessment of these antibiotics was conducted. Results All five types of antibiotics were detected in the source water of Yichang City, and the detection rate was 6.25% to 81.25%. The total detection rate of β-lactam antibiotics was the highest, and the highest detection concentration of norfloxacin was 213.9 ng/L. The health risk assessment of 11 antibiotics detected in the source water showed that these antibiotics would not cause obvious health harm to human body, but the risk entropy (RQ_H) tended to increase with the younger age. Conclusion The distribution level of antibiotics in source water of Yichang City will not cause obvious health harm to human body.

Organoid is a newly developed cellular there-dimensional culture system in recent years. Organoids have a three-dimensional structure, which is similar to that of the real organs. Together with the characteristics of self-renewal and reproduction of tissue origin, organoids can better simulate the function of real organs. Organoids provide a new platform for the study of organogenesis, regeneration, disease pathogenesis, and drug screening. The digestive system is an essential part of the human body and performs important functions. To date, organoid models of various digestive organs have been successfully established. This review summarizes the latest research progress of organoids of taste buds, esophagi, stomachs, livers and intestines, and prospects future application of organoids.
Humans ; Organoids ; Intestines ; Liver