Zhigang Huang

Head and neck mucosal melanoma is one of the most common types of melanoma in China, but the prognosis is worse than other types, and there is no effective treatment plan to improve patient survival. This study analyzes the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitor in the treatment of head and neck mucosal melanoma, as well as its impact on the tumor immune microenvironment. NPSG mice were used to construct a humanized bilateral lesion tumor model of the humanized immune system. The models were divided into an RT (8 Gy)+anti PD-1 group, an RT (2 GyX4)+anti PD-1 group, an Anti PD-1 group, an RT (8 Gy) group, and a blank group. Differences in efficacy and immune cells in blood, lymph nodes, and tumor tissues were compared between different treatment groups. The treatment effect of RT (8 Gy)+anti PD-1 was better than the other groups with a tumor growth inhibition value (TGI) over 60%. Significant recruitment and activation of CD8+T cells were found in the blood, lymph nodes, and tumor tissues and significantly inhibited the level of PD-1+CD8+T cells in the group of RT (8 Gy)+anti PD-1. This study confirmed the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitors, which can inhibit tumor growth and produce distant effects. The appearance of a distant effect is related to the enhancement in the number and activity of CD8+T cells in the local tumor and peripheral blood and lymph nodes. This study confirms the therapeutic and immune regulatory effect of hypofractionation radiotherapy combined with PD-1 inhibitors.

Purpose To investigate the cross-sectional associations of daytime sleepiness with coronary plaque volume and composition in patients with obstructive sleep apnea (OSA), and whether or not these associations are modified by age, gender, and obesity. Methods Patients who were confirmed with OSA through respiratory polygraphy and also underwent coronary CTA at a tertiary hospital were consecutively enrolled. The interval between the sleep monitoring and coronary CTA scan was < 3 months. Every patient completed the Epworth sleepiness scale (ESS) to assess daytime sleepiness, and an ESS score of ≥ 11 was recognized as excessive daytime sleepiness (EDS). Coronary plaque volume and composition were measured using semi-automatic software. Results Of the 394 patients with OSA (median [IQR] age, 56.0 [49.0–64.0] years; median [IQR] body mass index, 27.9 [25.5–30.2] kg/m²; median [IQR] apnea–hypopnea index, 21.3 [11.7, 36.3] events/h), a total of 200 patients had EDS. In the overall participants, a significant dose–response relationship between ESS scores and low-attenuation plaque volume was found in the fully adjusted model (P = 0.019). Further analysis demonstrated that there was a significant interactive effect of ESS levels and obesity on coronary plaque volume (all P values for interaction analysis < 0.05). Specifically, ESS levels were associated with total plaque volume, volumes of noncalcified, low-attenuation, and calcified plaque (P = 0.008, 0.006, 0.005, and 0.043 respectively) in obese patients with OSA. Conclusion Daytime sleepiness is significantly correlated with increased coronary plaque burden among patients with OSA. Thus, clinicians should recognize that patients with OSA reporting high ESS scores, especially those with obesity, are more prone to experience adverse coronary events.

(1) Aim: We aim to evaluate the association between arousals during sleep and subclinical coronary atherosclerosis detected by coronary computed tomography angiography (CTA) in patients with obstructive sleep apnea (OSA). (2) Methods: This was a cross-sectional study. Consecutive newly diagnosed OSA patients, who underwent coronary CTA examinations within 3 months of the sleep study, were eligible. We used the arousal index (ArI) derived from polysomnography to assess arousals during sleep and a semi-automated plaque quantification software to characterize and quantify the subclinical coronary atherosclerosis. Multiple regression models were used to evaluate the associations of the ArI with the coronary atherosclerotic plaque presence, volume, and composition. (3) Results: A total of 99 patients with OSA were included in the study. In the multivariable models, patients with a high ArI (ArI > 32.2 events/h) were more likely to have coronary plaques compared to those with a low ArI (ArI ≤ 32.2 events/h) (OR: 3.29 [95% CI: 1.284 to 8.427], p = 0.013). Furthermore, the ArI exhibited significant associations with total (β = 0.015), noncalcified (β = 0.015), and low-attenuation (β = 0.012) coronary plaque volume after accounting for established risk factors (p = 0.008, 0.004, and 0.002, respectively). However, no association between the ArI and calcified plaque volume was found. (4) Conclusion: Repetitive arousals during sleep are associated with an increased coronary plaque burden in patients with OSA, which remained robust after adjusting for multiple established cardiovascular risk factors.

Background: Although poorly differentiated is rare in head and neck squamous cell carcinoma (HNSCC), its prognosis are worse with high rate of local recurrence and distant metastasis (DS). Therefore, this study hopes to carry out prospective clinical research on different treatment options for poorly differentiated patients and explore the treatment scheme more suitable for these patients. Methods: This study is a prospective cohort study. We selected patients with poorly differentiated carcinoma in larynx or hypopharynx (stage I–IV, T1–4a, N0–2, M0). The intervention treatment methods for stage I–II patients are as follows: surgery, induction chemotherapy (IC) + surgery, surgery + adjuvant therapy; The intervention treatment methods for stage III–IV patients are as follows: surgery, IC + surgery + adjuvant therapy, surgery + adjuvant therapy. The patients were followed up for at least 1 year, and the disease progression and survival were counted. Results: From September 2016 to October 2020, 62 patients were included (29 patients in stage I/II and 33 patients in stage III/IV). We found that there was no significant difference in survival between treatment groups in stage I/II patients [overall survival (OS): P=0.447; progression free survival (PFS): P=0.504], but the surgery + adjuvant treatment group had a significant advantage in 3-year OS (100%). In stage III/IV patients, there were significant differences in DS, OS and PFS between different treatment groups (DS: P=0.013; OS: P=0.021; PFS: P=0.020). Among them, the survival rate of IC + surgery + adjuvant treatment group was the best, with 3-year OS of 78%. Conclusions: Our study found that postoperative radiotherapy may improve the OS rate of patients with early (stage I/II) poorly differentiated HNSCC; For advanced patients (stage III/IV), surgery combined with IC and postoperative adjuvant radiotherapy may better control DS and improve the survival rate. However, our study draws the above conclusions based on small sample data, and we will continue to summarize and expand the sample size for verification.

The purpose of this study is to review the efficacy of radiotherapy combined with immune checkpoint inhibitors (ICIs) in the treatment of melanoma and systematically evaluate the efficacy and safety of this combined treatment compared with ICIs alone. We searched a number of online databases up to 1 July 2021. Comprehensive Meta-Analysis 2.0 and RevMan 5.0 were used for summary analysis. The overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and treatment adverse effects (AEs) were calculated. In total, 624 patients were included from 12 studies, including nine published studies and the results of three clinical trials. Radiotherapy combined with ICIs had a higher ORR compared with ICIs alone (35.00 vs. 20.39%). In terms of survival effect, radiotherapy combined with ICIs had no obvious advantage in OS. There was no statistically significant difference between 6-month and 12-month OS (P = 0.13; P = 0.69). There was no significant difference in PFS at 6 months (P = 0.08), but there was a significant difference in PFS at 12 months (P = 0.005). For patients with melanoma, radiotherapy combined with ICIs can improve the effective rate of treatment. Although there is no obvious OS advantage, it can improve PFS without serious adverse effects. Most of the studies included in this article are retrospective analyses, and there are few randomized controlled studies at present. Therefore, more prospective studies are still needed to explore the efficacy of radiotherapy combined with immunotherapy in melanoma.

Background: This study sought to establish a rat model of hypoparathyroidism by removing the rat parathyroid glands, and compare the effects of different transplantation sites and transplantation methods using a primary culture of parathyroid cells in vitro on the hormone secretion of the model rats. Methods: Male Sprague Dawley (SD) rats were selected for in vivo parathyroid gland removal, and rats with abnormal postoperative water intake, weight gain, parathyroid hormone (PTH), and blood calcium ion concentration were selected as transplant recipients and divided into the model group, brachioradialis muscle cell transplantation group, gelatin sponge group, and subcutaneous transplantation group. The parathyroid tissue was removed and the primary cell culture was performed in vitro using homozygous SD rats as graft donors. When the parathyroid cells were able to secrete PTH, transplantation was performed, and the postoperative recovery of the PTH function of the rats with different transplantation sites and methods were observed. Results: A recipient model with low PTH was successfully established, and parathyroid progenitor cells with obvious PTH secretion were obtained. Better secretion was observed in the brachioradialis cell group compare with other groups. Conclusions: The in vitro primary cell culture of the donor parathyroid cells combined with cell transplantation significantly improved the physiological function of the hypoparathyroid rats, and could potentially replace traditional clinical brachioradialis muscle tissue transplantation.

Wallerian degeneration (WD) involves the recruitment of macrophages for debris clearance and nerve regeneration, and the cause of the foamy macrophages that are frequently observed in peripheral transection injuries is unknown. Recent studies indicated that these foamy cells are generated by gasdermin D (GSDMD) via membrane perforation. However, whether these foamy cells are pyroptotic macrophages and whether their cell death elicits immunogenicity in peripheral nerve regeneration (PNR) remain unknown. Therefore, we used GSDMD-deficient mice and mice with deficiencies in other canonical inflammasomes to establish a C57BL/6 J mouse model of sciatic nerve transection and microanastomosis (SNTM) and evaluate the role of GSDMD-executed pyroptosis in PNR. In our study, the GSDMD^−/− mice with SNTM showed a significantly diminished number of foamy cells, better axon regeneration, and a favorable functional recovery, whereas irregular axons or gaps in the fibers were found in the wild-type (WT) mice with SNTM. Furthermore, GSDMD activation in the SNTM model was dependent on the NLRP3 inflammasome and caspase-1 activation, and GSDMD-executed pyroptosis resulted in a proinflammatory environment that polarized monocytes/macrophages toward the M1 (detrimental) but not the M2 (beneficial) phenotype. In contrast, depletion of GSDMD reversed the proinflammatory microenvironment and facilitated M2 polarization. Our results suggested that inhibition of GSDMD may be a potential treatment option to promote PNR.

Oral/head and neck cancer is the sixth most common human malignancies in the world. Despite the treatment advances in surgery, chemotherapy, and radiotherapy, the patient survival has not been significantly improved in the past several decades. As a new methodological approach, metabolomics may help reveal the metabolic reprogramming mechanisms underlying head and neck cancer cell proliferation, invasion, and metastasis and may be used to identify metabolite biomarkers for clinical applications of the disease. In this chapter, we briefly review recent metabolomic applications in head and neck cancer.