Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Study on carotid artery stenosis after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: This study investigated carotid artery stenosis (CAS) and associated risk factors in patients with nasopharyngeal carcinoma (NPC) post-radiotherapy. MATERIALS AND METHODS: The observation group comprised 86 reexamined patients with NPC, divided into Group 1 and Group 2 based on post-radiotherapy duration, alongside 34 newly diagnosed patients with NPC (Group 0). Carotid artery ultrasonography and chi-square analysis were performed. RESULTS: Moderate-to-severe vascular abnormalities were exclusively in Group 2. Considering mild vascular abnormalities as the standard, the overall vascular abnormality rates in Group 2 and Group 0 were 65.9% and 41.2%, respectively. In Group 2 and Group 0, the abnormality rates for unilateral carotid artery (UCA), common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA) were 47.4% and 30.9%, 44.3% and 22.1%, 44.3% and 16.2%, and 39.8% and 5.9%, respectively. Comparing group 1 to group 0, only UCA abnormalities were statistically significant (45.4% vs. 30.9%). Considering moderate-to-severe vascular abnormalities as the standard, Group 2 had higher overall vascular, UCA, CCA, ICA, and ECA abnormality rates compared to Group 0. The age at revisit over 45 years, T stage, and N stage may influence CAS. CONCLUSION: Radiation increasing CAS incidence after 3 years. So, regular examinations are recommended to dynamically monitor CAS after 3 years of radiotherapy.

Prediction of severe radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma using the combined systemic immune-inflammatory index and prognostic nutritional index.

OBJECTIVE: Severe radiation-induced oral mucositis (sRIOM) can seriously affect patients' quality of life and treatment compliance. This study was to investigate the utility of the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) in predicting sRIOM in patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: 295 patients with LANPC were retrospectively screened. The pre-radiotherapy SII and PNI were calculated based on peripheral blood samples. A receiver operating characteristic (ROC) curve was used to determine the cut-off value. Logistic regression was used for univariate and multivariate analyses. Patients were classified into three groups based on the SII-PNI score: score of 2, high SII (> cut-off value) and low PNI (≤ cut-off value); score of 1, either high SII or low PNI; score of 0, neither high SII nor low PNI. RESULTS: The SII-PNI demonstrated significant predictive ability for sRIOM occurrence, as evidenced by an area under the curve (AUC) of 0.738. The incidence rates of sRIOM with SII-PNI score of 2, 1, and 0 were 73.86%, 44.35%, and 18.07%, respectively. Multivariate analysis confirmed that the SII-PNI score was an independent risk factor for sRIOM. CONCLUSION: The SII-PNI score is a reliable and convenient indicator for predicting sRIOM in patients with LANPC.

Dickkopf-1 is an immune infiltration-related prognostic biomarker of head and neck squamous cell carcinoma.

Immunotherapy is currently one of the most viable therapies for head and neck squamous cell carcinoma (HNSCC), characterized by high immune cell infiltration. The Wnt-signaling inhibitor and immune activation mediator, Dickkopf-1 (DKK1), has a strong correlation with tumor growth, tumor microenvironment, and, consequently, disease prognosis. Nevertheless, it is still unclear how DKK1 expression, HNSCC prognosis, and tumor-infiltrating lymphocytes are related. To better understand these associations, we examined how DKK1 expression varies across different tumor and normal tissues. In our study, we investigated the association between DKK1 mRNA expression and clinical outcomes. Next, we assessed the link between DKK1 expression and tumor immune cell infiltration. Additionally, using immunohistochemistry, we evaluated the expression of DKK1 in 15 healthy head and neck tissue samples, and the expression of CD3, CD4, and DKK1 in 27 HNSCC samples. We also explored aberrant DKK1 expression during tumorigenesis. DKK1 expression was remarkably higher in HNSCC tissues than in healthy tissues, and was shown to be associated with tumor stage, grade, lymph node metastasis, histology, and a dismal clinical prognosis in HNSCC. DKK1 expression in HNSCC tissues was inversely correlated with CD3+ (P < 0.0001) and CD4+ (P < 0.0001) immune cell infiltration, while that in immune cells was inversely associated with HNSCC prognosis. These findings offer a bioinformatics perspective on the function of DKK1 in HNSCC immunotherapy and provide justification for clinical research on DKK1-targeted HNSCC treatments. DKK1 is a central target for improving the efficacy of HNSCC immunotherapy.

Mutation analysis of the TGFBI gene in pedigrees of lattice corneal dystrophy in Eastern China.

BACKGROUND: To delineate the mutations of the TGFBI gene in Eastern China by whole-exome sequencing (WES) in eight Chinese families with lattice corneal dystrophy (LCD). MATERIALS AND METHODS: This retrospective study included eight families with LCD from Eastern China. Clinical features were examined using slit-lamp examination, anterior segment optical coherence tomography, and in vivo confocal microscopy. Peripheral blood samples of probands were collected for WES, and saliva samples from family members were collected for TGFBI screening using Sanger sequencing. The physicochemical effects of mutations were investigated using bioinformatics tools. RESULTS: Family 1 presented a classic LCD I with a p.R124C mutation of the TGFBI gene, while the other seven families were diagnosed with LCD IIIA. Six of the seven LCD IIIA families had heterozygous single-gene mutations (p.A546D, p.L565 H, p.T621P), and one had a compound heterozygous (cis) mutation (p.P501T and p.N622 H). The mutation of p.L565 H was the first time of integrated family report in contrast to the cases reported in 2019, and the p.T621P mutation was first reported in a Chinese population. Notably, the family with the compound mutation was associated with an obvious early-onset (in the 2nd decade of life) compared to the LCD IIIA patients with each single mutation (p.P501T or p.N622 H) showing late-onset (in the 7th decade of life). CONCLUSIONS: WES is efficient for the genomic testing of LCD and genetic relationship identification in different families with the same mutated gene. We identified a compound heterozygous mutation (p.P501T and p.N622 H) and two mutations (p.T621P and p.L565 H) uncommon in China.

Puerarin inhibits the development of osteoarthritis through antiinflammatory and antimatrix-degrading pathways in osteoarthritis-induced rat model.

Puerarin is an isoflavone isolated from the medicinal plant Pueraria lobata. The purpose of this study was to study the antiinflammatory and antimatrix-degrading effects of puerarin in a rat osteoarthritis (OA) model and its protective effects on joints. The rat OA model was established by anterior cruciate ligament transection (ACLT) surgery. Rats (n = 40) were divided into nontreated OA, OA + celecoxib (2.86 mg/kg), OA + puerarin (50 and 100 mg/kg), and control groups. Two weeks after surgical induction, puerarin was administered by gavage daily for 8 weeks. After 8 weeks, macroscopic observation and histopathological images showed that cartilage damage was reduced after puerarin and celecoxib treatment, the intensity of Safranin O staining was high, and the OARSI scores were significantly reduced compared to the OA group. Puerarin reduced the expression of MMP-3, MMP-13, ADAMTS-5, and COX-2 in the cartilage tissue of ACLT rats, inhibited the production of IL-1ß, IL-6, and TNF-α inflammatory factors, increased Type II collagen content, and altered the expression of serum OA cartilage degradation/bone turnover biomarkers (CTX-I, CTX-II, COMP, and PIINP). Based on these findings, we speculate that puerarin supplement to attain recovery from OA damage.

Effect of ketamine combined with DHA on lipopolysaccharide-induced depression-like behavior in rats.

Depression has become a common mental illness, and studies have shown that neuroinflammation is associated with depression. Ketamine is a rapid antidepressant. In order to obtain better antidepressant effects, it is necessary to explore the efficacy of combination therapy with ketamine and other antidepressants. DHA is an unsaturated fatty acid with excellent application prospects due to its safety and antidepressant effects. This study was designed to investigate the effect of ketamine combined with DHA on lipopolysaccharide-induced depression-like behavior. In behavioral experiments, lipopolysaccharide prolongs the immobility time of the forced swimming and tail suspension tests in rats and reduces the sucrose preference. The combination of ketamine and DHA can reverse these changes and work better than the single application. Nissl staining showed that ketamine combined with DHA can reverse the nerve damage caused by lipopolysaccharide. Cell morphology observation the combination of ketamine and DHA group was more complete than that of LPS group. The combination of ketamine and DHA significantly decreased the levels of IL-1, IL-6 and TNF-ɑin hippocampus and PC12 cells and increased the content of BDNF. Immunofluorescence results showed that ketamine combined with DHA can effectively inhibit PP65 nuclear translocation. Western blot results showed that ketamine combined with DHA can effectively inhibit the expression of NF-KB in hippocampus and PC12 cells, and increase the expression of P-CREB and BDNF. In summary, the combination of ketamine with DHA may be a more effective treatment for depression caused by inflammation and is mediated by inhibition of the inflammatory pathway.

Neoadjuvant Chemotherapy Based on Abraxane/Human Neutrophils Cytopharmaceuticals with Radiotherapy for Gastric Cancer.

Gastric cancer remains one of the most lethal cancers with high incidence and mortality worldwide. The majority of gastric cancer patients are those who have first been diagnosed in advanced stage, in which the standard chemo-radiotherapy produces limited benefit along with severe general toxicity, thus the demand for improved therapeutic efficacy and decreased side effects drives the development of novel therapeutic strategies. Here, a neoadjuvant chemotherapy based on Abraxane/human neutrophils (NEs) cytopharmaceuticals with radiotherapy is presented for effective cancer treatment. Human NEs, the most abundant white blood cells in peripheral blood, are developed to carry Abraxane, the commercial albumin-bound paclitaxel nanoparticle, to form cytopharmaceuticals (Abraxane/NEs) which have been confirmed to maintain the intrinsic functions of human NEs. The modest radiation is applied not only to exert tumor disruption, but also to increase the release of inflammatory factors which guide the NEs homing to the tumoral sites. These amplified inflammatory factors at tumor sites excessively activate Abraxane/NEs to form neutrophil extracellular traps, along with a burst release of Abraxane to induce superior tumor suppression. This adjuvant chemo-radiotherapy based on cytopharmaceuticals may provide new opportunities for advanced cancer treatment, which reveals the huge clinical potential of human neutrophils as drug delivery vectors.

Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence.

Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain. The highly concentrated inflammatory signals in the brain trigger the release of liposomal PTX from the NEs, which allows delivery of PTX into the remaining invading tumour cells. We show that this NE-mediated delivery of drugs efficiently slows the recurrent growth of tumours, with significantly improved survival rates, but does not completely inhibit the regrowth of tumours.