Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Traditional breast implant insertion method can pose risks of infection, incisional damage, mechanical damage to the implant, and other complications that can cause problems for both plastic surgeons and patients. In recent years, some scholars have applied the "no-touch" breast implant insertion devices to the surgery in order to solve these problems. This article reviews the types, advantages and disadvantages of the "no-touch" breast implant insertion devices and their development trends to provide a reference for plastic surgeons to perform implant-based breast surgery, thus improving the efficiency and safety the operation.

Traditional breast implant insertion method can pose risks of infection, incisional damage, mechanical damage to the implant, and other complications that can cause problems for both plastic surgeons and patients. In recent years, some scholars have applied the "no-touch" breast implant insertion devices to the surgery in order to solve these problems. This article reviews the types, advantages and disadvantages of the "no-touch" breast implant insertion devices and their development trends to provide a reference for plastic surgeons to perform implant-based breast surgery, thus improving the efficiency and safety the operation.

Objective:To evaluate the effects of different types of psychological interventions on the fear of cancer recurrence through a network Meta-analysis.Methods:Randomized controlled trials on the effects of different types of psychological interventions on the fear of cancer recurrence were retrieved from PubMed, PsycINFO, Web of Science, The Cochrane Library, Embase, EBSCO, China Biomedical Literature Database, CNKI, Wanfang Database and Vip Database. The retrieval period was from the establishment of the database to December, 31 2022. Two researchers conducted literature screening, extraction and quality evaluation, and used Stata14.0 software to conduct network Meta-analysis.Results:A total of 29 pieces of research involving 3 068 cancer patients and 11 psychological intervention measures. The results of network Meta-analysis showed that narrative therapy, PERMA(Positive, Engagement, Relationship, Meaning, Accomplishment) happiness theory model, acceptance and commitment therapy and cognitive behavior therapy had statistically significant differences in the intervention effect on the fear of cancer recurrence compared with conventional nursing ( SMD values were -1.93--0.83, all P<0.05); there was no significant difference among narrative therapy, PERMA happiness model, acceptance and commitment therapy and gratitude-expansion behavior theory (all P>0.05). The results of the cumulative probability map showed the best intervention was narrative therapy. Conclusions:The results of this study suggest that narrative therapy, acceptance and commitment therapy, and cognitive behavior therapy may be effective psychological intervention measures to improve the fear of cancer recurrence. However, more studies are still needed for further verification.

Acute kidney injury(AKI)is a common perioperative complication,which is associated with an increased incidence rate of other postoperative complications and death risk of the patients.Remote ischemic preconditioning(RIPC)performs multiple transient ischemia/reperfusion cycles at remote sites far from the target organs to enhance the tolerance of target organs to oxidative stress.A large number of animal experiments have shown that RIPC can improve kidney function,alleviate AKI,and increase the survival rate of AKI patients.However,there is still controversy about the mechanism of RIPC in alleviating AKI in clinical studies.In this article,the research progress on the role and mechanism of RIPC in renal protection in recent years is reviewed,in order to provide a reference for further exploration of perioperative renal protection strategies and mechanisms.

Objective:To analyze clinical efficacy, failure mode and prognostic factors of nasopharyngeal carcinoma (NPC) patients undergoing intensity modulated radiation therapy (IMRT).Methods:Clinical data of 951 locally advanced NPC patients who were newly-treated with IMRT in Hunan Cancer Hospital from January 2018 to January 2019 were retrospectively analyzed. The patients' general data, overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), local recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were analyzed. Comparison among different groups was performed by one-way ANOVA. Survival rate was calculated by Kaplan-Meier method. Survival difference was compared by log-rank test. Univariate and multivariate analyses were performed by Cox regression model.Results:The median follow-up time was 62.0 months (IQR, 58.0-65.0 months). The 5-year OS, LRFS, RRFS, LRRFS, DMFS, and PFS were 85.4%, 94.0%, 97.7%, 92.6%, 85.7% and 76.9%, respectively. According to the 8th edition staging of American Joint Committee on Cancer (AJCC), there were 10 cases (1.1%) of stage I, 76 cases (8.0%) of stage II, 445 cases (46.8%) of stage III, and 420 cases (44.2%) of stage IVA, respectively. Among them, the OS rates of stage I, II, III and IVA patients were 100%, 97.2%, 88.8% and 79.2%, respectively ( P<0.001); LRRFS rates were 100%, 90.4%, 94.7% and 90.4%, respectively( P=0.104); DMFS rates were 90.0%, 95.9%, 88.0% and 81.1%, respectively ( P<0.001); PFS rates were 90.0%, 89.1%, 80.9% and 70.1% respectively ( P<0.001). There were 183 cases of treatment failure, including 52 cases (5.5%) of local failure, 19 cases (2.0%) of regional failure, 130 cases (13.7%) of distant metastasis, 16 cases of local combined with regional failure (1.7%), 16 cases (1.7%) of local failure combined with distant metastasis, 13 cases (1.4%) of regional failure combined with distant metastasis, and 9 cases (0.9%) of local regional failure combined with distant metastasis, respectively. Multivariate regression analysis suggested that EB virus DNA copy number before treatment, T stage and N stage were the independent prognostic factors affecting OS, DMFS and PFS. Conclusions:Compared with two-dimensional radiotherapy, IMRT has improved the overall therapeutic effect for NPC, especially the local control rate. Distant metastasis is still the main failure mode. Clinical staging, prognostic risk stratification and prognostic biomarkers can be combined to deliver stratified and precise treatment, which may further improve clinical efficacy and reduce treatment-related side effects.