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.

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

The research on the cardiovascular toxicity of air pollutants is in urgent need of collaborative innovation across multiple models. This paper systematically reviewed the advantages and limitations of four principal research models of cardiotoxicity, including epidemiological model, mammalian model, zebrafish model, and in vitro model. Epidemiological models have been used to demonstrate a significant correlation between exposure to PM_2.5 and both the incidence and mortality of cardiovascular diseases within populations; however, these models face challenges in establishing causal inferences and interpreting individual mechanisms. Mammalian models have been applied to elucidate the pathogenic mechanisms of PM_2.5 at both the systemic and organ-specific levels, yet they encounter difficulties related to interspecies differences and throughput constraints. Zebrafish models, with their transparent embryos and observable development, offer a distinctive opportunity for high-throughput screening and mechanistic investigation of PM_2.5-induced cardiac developmental toxicity. Nonetheless, their cardiac physiological structure diverges from that of mammals, limiting their capacity to accurately model chronic conditions such as coronary heart disease. In vitro models, particularly human heart organoids and chip technologies, have provided profound insights into the direct toxic mechanisms of PM_2.5, including disruptions in calcium homeostasis, cellular senescence, and electrophysiological irregularities at the cellular and molecular levels. Despite these advancements, the complexity and developmental maturity of these models present challenges to their broader application. This paper proposed that the key to overcoming the bottlenecks of single models lies in the construction of an integrated evaluation system that combines “epidemiological studies, mammalian models, zebrafish models, and in vitro models”. By focusing on three aspects, namely model integration, technological convergence, and policy support, it is intended to collaboratively address issues such as standardization of multi-model data, simulation of complex exposure scenarios and susceptible life stages, and transformation pathways. This will provide innovative methodological support for the analysis of the cardiotoxic mechanisms of air pollutants, the assessment of environmental health impacts, and the formulation of precise prevention and control strategies.

The anterior cruciate ligament (ACL), anterolateral complex (ALC) and lateral meniscus (LM) maintain the anterolateral rotatory stability of the knee and control the internal rotation of the tibia. Anterolateral rotatory instability (ALRI) of the knee is not uncommon in clinic, and its main injury mechanism is non-contact injury. A pivot shift test or a tibial internal rotation test can indicate ALRI while X-ray, CT, MRI and ultrasound can assist in its diagnosis and differential diagnosis. For acute ALRI, good technique of ACL reconstruction is the basis to avoid postoperative residual ALRI, and anterolateral ligament reconstruction and extra-articular tenodesis are optional as appropriate. For chronic cases, however, both anterolateral ligament reconstruction and extra-articular tenodesis are effective. This article reviews the progress in research on the diagnosis and treatment of ALRI of the knee, hoping to provide references for its clinical diagnosis and treatment.

Objective To analyze the short-term clinical efficacy and prognosis of one-stop transcatheter aortic valve replacement (TAVR)+percutaneous coronary intervention (PCI) in the treatment of aortic valve disease with coronary heart disease. Methods The clinical data of patients with aortic valve disease complicated with coronary heart disease who underwent one-stop TAVR+PCI treatment at the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from January 2018 to June 2023 were retrospective analyzed. The preoperative and postoperative clinical data were compared, and 1-month follow-up results were recorded. Results A total of 37 patients were enrolled, including 22 males and 15 females, with an average age of 69.14±6.47 years. Thirty-six patients recovered and were discharged after the surgery, and 1 (2.7%) patient died during the surgery. Self-expanding TAVR valves were implanted through the femoral artery in all patients. One coronary artery was opened by PCI in 35 (94.6%) patients, and two coronary arteries were opened by PCI in 2 (5.4%) patients. All PCI opened arteries had a stenosis>70%. During the postoperative hospitalization, the complications included pulmonary infection in 11 (30.6%) patients, severe pneumonia in 10 (27.8%) patients, liver function injury in 14 (38.9%) patients, renal function injury in 5 (13.9%) patients, cerebral infarction in 1 (2.8%) patient, atrial fibrillation in 1 (2.8%) patient, ventricular premature beats in 2 (5.6%) patients, atrioventricular block in 2 (5.6%) patients, and complete left bundle branch block in 5 (13.9%) patients. The median postoperative ventilation assistance time was 12.0 (0.0, 17.0) h, the ICU monitoring time was 1.0 (0.0, 2.0) d, and the postoperative hospitalization time was 5.0 (4.0, 7.0) d. There was a significant improvement in the New York Heart Association cardiac function grading after surgery (P<0.001). After surgery, there were 21 (58.3%) patients had minor perivalve leakage, 6 (16.7%) patients had minor to moderate perivalve leakage, and no moderate or above degree of perivalve leakage. After one month of postoperative follow-up, 36 patients showed significant improvement in heart function. There were no patients with recurrent acute coronary syndrome, re-PCI, or cardiovascular system disease related re-hospitalization. Conclusion The one-stop TAVR+PCI treatment for patients with aortic valve disease and coronary heart disease can obtain satisfactory short-term clinical efficacy, which is worth further trying and studying.

This paper reports a case of reparing the tissue defect after resection of a malignant tumor in the glabellar nasion with bilateral modified horizontal advancement flaps. The patient, a 20-year-old female, was admitted to the hospital because of a mass on the nasion between the eyebrows for more than 5 years, with enlargement and ulceration for 5 months. Surgical resection of the tumor was performed. Intraoperative rapid frozen sections showed that the tumor was basal cell carcinoma, and there were no cancer cells at the margins. Bilateral modified horizontal advancement flap repair was performed. At three months after the operation, the incision area healed well, the appearance and eyelid function were normal, and there was no sign of recurrence of basal cell carcinoma. Bilateral modified horizontal advancement flap was effective in repairing the tissue defect after resection of glabellar nasal root basal cell carcinoma.

Objective:To explore the surgical effects of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty.Methods:A retrospective study was conducted on patients who underwent the operation of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty at the Department of Plastic and Aesthetic Surgery of Qingdao Municipal Hospital from September 2021 to September 2023. Six points were marked on the skin surface of the designed double eyelid line on patient' s upper eyelid, 8 points were marked on the corresponding conjunctival surface of the designed double eyelid line. A 6-0 nylon thread attached with one needle on each end was used for suturing, with two ends running through and between the subcutaneous and subconjunctival layers alternatively, forming a " trapezoidal" shape of path. Finally, two ends exited at the same point on the most lateral side of the designed double eyelid line on skin surface and were tied together with the knot hidden within the orbicularis oculi muscle. The morphology of the double eyelids and postoperative complications were observed and evaluated after surgery, the follow-up period was at least 6 months. At the last time of follow-up, the satisfaction rates were evaluated by patients themselves. Four aspects of the surgical effects of the double eyelids were put into the evaluation system, which were radian, width, smoothness and symmetry, with score from 0-5 points for each. The total score was 0-20 points, of which 17-20 points indicated high satisfaction, score of 13-16 points indicated relative satisfaction, ≤ 12 points indicated dissatisfaction.Results:A total of 52 female patients were included, aged 18 to 29 years old, with an average age of 22.5 years. Among all patients, 33 cases had shallow double eyelid lines while 19 cases had single eyelids. All patients’ upper eyelids were relatively thin and without obvious looseness. The surgical procedures were all done smoothly and successfully, with an average operation time of (0.72±0.13) h. Immediately after surgery, the radian of the double eyelid lines on both sides looked smooth, the widths of the double eyelids were also basically symmetrical. During the follow-up period of 6-12 months postoperatively, the morphologies of the double eyelids were relatively natural and realistic, the double eyelid lines and widths remained deep and stable, and the incision scars were left unobvious for all patients. Besides, no complications such as ptosis, incomplete upper eyelid closure and ectropion were observed. Among the 52 patients, 45 cases were highly satisfied with the surgical result (17-20 points) , 7 were relatively satisfied (13-16 points) , while none of them required reoperation.Conclusions:The continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty has advantages of short operation time, good and stable surgical effects such as natural and realistic morphology of double eyelids, few complications, and high patients' satisfaction rate.

Objective:To explore the surgical effects of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty.Methods:A retrospective study was conducted on patients who underwent the operation of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty at the Department of Plastic and Aesthetic Surgery of Qingdao Municipal Hospital from September 2021 to September 2023. Six points were marked on the skin surface along the designed double eyelid line on patient’s upper eyelid, 8 points were marked on the corresponding conjunctival surface along the designed double eyelid line. A 6-0 nylon thread attached with one needle on each end was used for suturing, with two ends running through and between the subcutaneous and subconjunctival layers alternatively, forming a "trapezoidal" shape of path. Finally, two ends exited at the same point on the most lateral side of the designed double eyelid line on skin surface and were tied together with the knot hidden within the orbicularis oculi muscle. The morphology of the double eyelids and postoperative complications were observed and evaluated after surgery, the follow-up period was at least 6 months. At the last time of follow-up, the satisfaction rates were evaluated by patients themselves. Four aspects of the surgical effects of the double eyelids were put into the evaluation system, which were radian, width, smoothness and symmetry, with score from 0-5 points for each. The total score was 0-20 points, of which 17-20 points indicated high satisfaction, 13-16 points indicated relative satisfaction, ≤12 points indicated dissatisfaction.Results:A total of 52 female patients were included, aged 18 to 29 years old, with an average age of 22.5 years. Among all patients, 33 cases had shallow double eyelid lines while 19 cases had single eyelids. All patients’ upper eyelids were relatively thin and without obvious looseness. The surgical procedures were all done smoothly and successfully, with an average operation time of (0.72±0.13) h. Immediately after surgery, the radian of the double eyelid lines on both sides looked smooth, the widths of the double eyelids were also basically symmetrical. During the follow-up period of 6-12 months postoperatively, the morphologies of the double eyelids were relatively natural and realistic, the double eyelid lines and widths remained deep and stable, and the incision scars were unobvious for all patients. Besides, no complications such as ptosis, incomplete upper eyelid closure and ectropion were observed. Among the 52 patients, 45 cases were highly satisfied with the surgical result, 7 cases were relatively satisfied, while none of them required reoperation.Conclusion:The continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty has advantages of short operation time, good and stable surgical effects such as natural and realistic morphology of double eyelids, few complications, and high patients’ satisfaction rate.