Objective To analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective To analyze the clinical application value of cinematic rendering(CR)reconstruction technology in acute aortic dissection(AAD),and to compare the imaging quality between CR and volume rendering(VR)reconstruction.Methods Patients with suspected A AD who underwent aortic computed tomography angiography(CTA)were analyzed retrospectively.All images were uploaded to Siemens Syngo.via post-processing workstation for VR and CR three-dimensional reconstruction,respectively.The optimized view angle,staining and transparency were selected and segmented by a radiologist to display the lesion to the full extent.All subjective evaluations of post-processing images were randomly evaluated on Siemens Syngo.via post-processing workstation by two radiologists.The two radiologists reached a consensus after consultation,and the results without consensus were evaluated by another senior radiologist.The 3-point scale was used in the subjective evaluation of post-processing images.The scores of rupture,endometrium,and true and false cavity were recorded.The diagnostic confidence was also recorded.Results A total of 21 ADD patients were enrolled,11 patients(52.3％)were Debakey Ⅲ type.The scores of rupture in CR and VR reconstruction were 2.952 points and 2.619 points,respectively,which had significant difference(P=0.016).For the endometrium of AAD,the score of all 21 patients in the CR reconstruction was 3 points,while only 7 patients(33.3％)in the VR reconstruction had 3 points,which showed significant difference between the both(P＜0.001).For the true and false cavity of AAD,only 1 patient(4.8％)in the VR reconstruction was 3 points,while all 21 patients in the CR reconstruction had 3 points(P＜0.001).The scores of CR reconstruction on the diagnostic confidence were significantly higher than those of VR reconstruction(P＜0.001).Conclusion CR reconstruction can provide photorealistic anatomical post-processing images,and can improve the display and evaluation of AAD.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective:To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness.Methods:This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives.Results:30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day.Conclusions:Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

ObjectiveTo explore the association between telomere length of leukocytes and chronic heart failure （CHF）. MethodsA total of 224 patients were recruited in this study. The patients were divided into non-CHF （Non-CHF） group （involving 117 patients） and CHF group （involving 107 patients） according to left ventricular ejection fraction. Telomere length of peripheral blood leukocytes was measured by real-time fluorescence quantitative polynucleotide chain reaction （qPCR）. Telomere length of leukocytes was compared between Non-CHF group and CHF group. Binary Logistic regression model was used to analyze the association between telomere length and CHF. ResultsTelomere length in Non-CHF patients and CHF patients was 0.9（0.64~1.18）， 0.7（0.53~0.89）， respectively. Telomere length was shorter in CHF patients than in Non-CHF patients （P<0.001）. Further results showed that telomere length was associated with CHF ［OR=0.17， 95% CI was （0.07， 0.40）， P<0.05］. After adjusting confounding factors， telomere length was still associated with CHF ［OR=0.14， 95% CI was （ 0.05， 0.33）， P<0.05］. ConclusionThe results show that telomere length of peripheral blood leukocytes is independently associated with CHF.

Objective: To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell. Methods: The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay. Results: ①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8⁺ T cell acquired dim expression of CD4 membrane protein after activation. CD4⁺T cell and CD8⁺CD4^dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01). Conclusions: CD4 targeted CAR-T has an immunophenotype of CD8⁺CD4^-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4⁺T cell and CD4⁺T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4^dim target cell.
CD4 Antigens ; CD8-Positive T-Lymphocytes ; Cell Line, Tumor ; Humans ; Lymphoma ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen