Helicobacter pylori infection increases risk of bleeding during endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is commonly used to treat early gastric cancer (EGC). The effects of Helicobacter pylori (HP) infection on ESD and the potential benefits of preoperative eradication of HP remain unclear. The study aims to evaluate the impact of HP infection on bleeding and lesion detection during ESD in patients with EGC. METHODS: We retrospectively analyzed 634 consecutive patients who underwent ESD for EGC at our center between January 2018 and January 2023. Logistic regression was used to assess the impact of HP infection status on intraoperative bleeding and lesion detection rates. We developed a predictive model based on selected indicators and evaluated its performance using the ROC curve. RESULTS: HP-positive patients experienced a higher rate of intraoperative bleeding (28.8%) compared with HP-negative patients (8.9%) (P < 0.001). HP-positive patients also had longer procedure time (median: 58.5 vs. 50.0 min, P < 0.001) and postoperative hospital stays (median: 4.35 vs. 4.07 days, P = 0.036). Multivariate analysis identified HP-positive (OR = 4.84), multiple lesions (OR = 1.81), specimen size > 40 mm (OR = 3.67), and submucosal invasion (OR = 2.27) as independent risk factors for intraoperative bleeding. The predictive model achieved an AUC of 0.807 (95%CI 0.761-0.852), with a sensitivity of 72.1% and specificity of 75.9%. Preoperative HP eradication was associated with an increased rate of lesion detection (OR = 2.82). CONCLUSIONS: Eradicating HP before ESD in patients with EGC reduces intraoperative bleeding and improves lesion detection. Preoperative HP eradication is therefore recommended in patients with EGC.

Case Report: Staged treatment of ankle deformity and first metatarsal deficiency after motorcycle spoke injury with Taylor external frame combined with fibular head grafting.

The treatment of the sequelae of severe foot injuries caused by motorcycle spoke injury, especially in pediatric patients, allows for new options and surgical protocols. The tarsometatarsal joint and the first metatarsal were reconstructed by precise preoperative design using the TSF space external fixation technique in one stage to correct the foot deformity and restore the volume and length, and free grafting of the fibular head with epiphysis in the second stage. This method is the first of its kind reported. The patient's foot deformity was corrected, walking, walking up and down stairs, and running functions were achieved, and the bone quality could grow with age. The combination of TSF six-axis spatial external fixation technique and microscopic technique can maximize the patient's appearance and function and is worth promoting.

Final analysis of a phase II trial of neoadjuvant chemoimmunotherapy for locoregionally advanced head and neck squamous cell carcinoma.

OBJECTIVES: Neoadjuvant chemoimmunotherapy has shown promising results for resectable, locoregionally advanced (LA) head and neck squamous cell carcinoma (L/A HNSCC). We published the first phase II trial of neoadjuvant camrelizumab combined with chemotherapy in resectable, L/A HNSCC, demonstrating it was safe and feasible with favorable pathological complete response (pCR). Here, we report the final analysis results for neoadjuvant chemoimmunotherapy in L/A HNSCC (minimum 2.0 years of follow-up). MATERIALS AND METHODS: Three cycles of chemoimmunotherapy were administered before surgery to patients with L/A HNSCC. Two-year disease-free survival (DFS), overall survival (OS) and quality of life (QOL) were reported. RESULTS: The overall two-year DFS and OS rates were 90 % and 100 %, respectively. With a median follow-up of 33.7 months, 9 of 10 (90 %) patients with pCR were alive and disease free. Patients with TNM stage (II/III) or < 20 % of residual viable tumor trended toward improved DFS; hazard ratio (HR), 0.44 [95 % confidence interval (CI), 0.04-5.28] and HR, 0.26 (95 % CI, 0.03-2.36), respectively. All QLQ-C30 functioning and symptom scales other than nausea and vomiting were resolved at 2 years after the completion of radiotherapy. CONCLUSION: Neoadjuvant camrelizumab in combination with chemotherapy provided encouraging clinical outcomes for patients with L/A HNSCC. Further studies with longer follow-up and larger samples are warranted. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1900025303. Registered Aug 22, 2019. https://www.chictr.org.cn/showproj.html?proj=41380.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

Interaction between long noncoding RNA and microRNA in lung inflammatory diseases.

BACKGROUND: Non-coding RNAs (ncRNAs) are a group of RNAs that cannot synthesize proteins, but are critical in gene expression regulation. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), the two major family members, are intimately involved in controlling immune response, cell proliferation, apoptosis, differentiation and polarization, and cytokine secretion. Their interactions significantly influence lung inflammatory diseases and could be potential therapeutic targets. OBJECTIVES: The review aims to elucidate the role of ncRNAs, especially the interactions between lncRNA and miRNA in lung diseases, including acute and chronic lung inflammatory diseases, as well as lung cancer. And provide novel insights into disease mechanisms and potential therapeutic methods. METHODS: We conducted a comprehensive review of the latest studies on lncRNA and miRNA in lung inflammatory diseases. Our research involved searching through electronic databases like PubMed, Web of Science, and Scopus. RESULTS: We explain the fundamental characteristics and functions of miRNA and lncRNA, their potential interaction mechanisms, and summarize the newly explorations on the role of lncRNA and miRNA interactions in lung inflammatory diseases. CONCLUSIONS: Numerous lncRNAs and miRNAs have been found to partipicate in all stages of lung inflammatory diseases. While ncRNA-based therapies have been validated and developed, there remain challenges in developing more stable and effective drugs for clinical use.

Injectable dexamethasone-loaded peptide hydrogel for therapy of radiation-induced ototoxicity by regulating the mTOR signaling pathway.

Radiation-induced ototoxicity is associated with inflammation response and excessive reactive oxygen species in the cochlea. However, the effectiveness of many drugs in clinical settings is limited due to anatomical barriers in the inner ear and pharmacokinetic instability. To address this issue, we developed an injectable hydrogel called RADA32-HRN-dexamethasone (RHD). The RHD hydrogel possesses self-anti-inflammatory properties and can self-assemble into nanofibrous structures, ensuring controlled and sustained release of dexamethasone in the local region. Flow cytometry analysis revealed that the uptake of FITC-conjugated RHD gel by hair cells increased in a time-dependent manner. Compared to free dexamethasone solutions, dexamethasone-loaded RHD gel achieved a longer and more controlled release profile of dexamethasone. Additionally, RHD gel effectively protected against the inflammatory response, reduced excessive reactive oxygen species production, and reversed the decline in mitochondrial membrane potentials induced by ionizing radiation, leading to attenuation of apoptosis and DNA damage. Moreover, RHD gel promoted the recovery of outer hair cells and partially restored auditory function in mice exposed to ionizing radiation. These findings validated the protective effects of RHD gel against radiation-induced ototoxicity in both cell cultures and animal models. Furthermore, RHD gel enhanced the activity of the mammalian target of rapamycin (mTOR) signaling pathway, which was inhibited by ionizing radiation, thereby promoting the survival of hair cells. Importantly, intratympanic injections of RHD gel exhibited excellent biosafety and do not interfere with the anti-tumor effects of radiotherapy. In summary, our study demonstrates the therapeutic potential of injectable dexamethasone-loaded RHD hydrogel for the treatment of radiation-induced hearing loss by regulating the mTOR signaling pathway.

Research progress on pharmacological effects and mechanisms of cepharanthine and its derivatives.

Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid compound found in plants of the Stephania genus, which has biological functions such as regulating autophagy, inhibiting inflammation, oxidative stress, and apoptosis. It is often used for the treatment of inflammatory diseases, viral infections, cancer, and immune disorders and has great clinical translational value. However, there is no detailed research on its specific mechanism and dosage and administration methods, especially clinical research is limited. In recent years, CEP has shown significant effects in the prevention and treatment of COVID-19, suggesting its potential medicinal value waiting to be discovered. In this article, we comprehensively introduce the molecular structure of CEP and its derivatives, describe in detail the pharmacological mechanisms of CEP in various diseases, and discuss how to chemically modify and design CEP to improve its bioavailability. In summary, this work will provide a reference for further research and clinical application of CEP.

Stabilizing oil-oil interfaces with mixed-shell polymeric nanoparticles prepared via PISA and the grafting combination.

The preparation of mixed-shell polymeric nanoparticles (MSPNs) and their stabilized non-aqueous Pickering emulsions was described in this study. Poly(methyl methacrylate)-poly(4-vinylpyridine) (PMMA-P4VP) diblock copolymer nanoparticles with different morphologies including spheres, worms and vesicles were first prepared via reversible addition-fragmentation chain transfer-based polymerization induced self-assembly in toluene. C18 alkyl chains were subsequently grafted onto the surfaces of the as-prepared PMMA-P4VP nanoparticles, affording C18/PMMA-P4VP MSPNs with P4VP blocks as the core and C18/PMMA chains as the mixed shells. MSPNs were utilized as Pickering emulsifiers to prepare non-aqueous Pickering emulsions, where [Bmim][PF6] and toluene oils were selected. Two kinds of different Pickering emulsions, [Bmim][PF6]-in-toluene and toluene-in-[Bmim][PF6], could be formed, depending on the initial location of MSPNs. However, neither of them could be generated when PMMA-P4VP diblock copolymer nanoparticles were adopted as Pickering emulsifiers, indicating MSPNs were better than diblock copolymer nanoparticle precursors in the aspect of stabilizing oil-oil interfaces. The formation mechanisms of different kinds of Pickering emulsions were unraveled in this study.

The efficacy and safety of apatinib in patients with heavily pretreated end-stage cancer: a retrospective study.

Background: Anti-angiogenesis therapy has been a vital treatment option in a variety of cancers. Assessing the efficacy and safety of apatinib in patients with heavily pretreated end-stage cancer is essential. Methods: Thirty patients with end-stage cancer who were heavily pretreated were enrolled in this study. All patients received oral administration of apatinib (125-500 mg/d) between May 2015 and November 2016. Dose reduction or elevation was conducted based on adverse events and doctors' judgments. Results: Prior to the apatinib treatment, the enrolled patients received a median of 1.2 surgeries (range, 0-7), 1.6 sessions of radiotherapies (range, 0-6), and 10.2 cycles of chemotherapy (range, 0-60); 43.3% of patients had uncontrolled local lesions, 83.3% of patients had uncontrolled multiple metastases, and 30.0% of patients had both. After the treatment, 25 patients had valuable data, 6 (24.0%) patients achieved partial response (PR), and 12 (48.0%) patients had stable disease (SD). The disease control rate (DCR) was 72.0%. The PR and SD rates were 20.0% and 40.0%, respectively, and the DCR was 60.0% in the intent-to-treat (ITT) analysis. Meanwhile, the median progression-free survival (PFS) was 2.6 (range, 0.7-5.4) months, and the median overall survival (OS) was 3.8 (range, 1.0-12.0) months. Furthermore, the PR rate and DCR in patients with squamous cell cancer (SCC) were 45.5% and 81.8%, respectively; those in patients with adenocarcinoma (ADC) were 8.3% and 58.3%, respectively. The adverse events were generally mild. The most common adverse events were hyperbilirubinemia (53.3%), elevated transaminase (36.7%), anemia (30.0%), thrombocytopenia (30.0%), hematuria (30.0%), fatigue (26.7%), and leukopenia (20.0%). Conclusions: The results of this study demonstrate the efficacy and safety of apatinib and support the further development of apatinib as a potential treatment option for patients with heavily pretreated end-stage cancer.

Development and validation of a novel nomogram to predict the overall survival of patients with large cell lung cancer: A surveillance, epidemiology, and end results population-based study.

Background: Large cell lung cancer (LCLC) is a rare subtype of non-small cell lung carcinoma (NSCLC), and little is known about its clinical and biological characteristics. Methods: LCLC patient data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. All patients were randomly divided into a training group and a validation group at a ratio of 7:3. The independent prognostic factors that were identified (P < 0.01) by stepwise multivariate Cox analysis were incorporated into an overall survival (OS) prediction nomogram, and risk-stratification systems, C-index, time-ROC, calibration curve, and decision curve analysis (DCA) were applied to evaluate the quality of the model. Results: Nine factors were incorporated into the nomogram: age, sex, race, marital status, 6th AJCC stage, chemotherapy, radiation, surgery and tumor size. The C-index of the predicting OS model in the training dataset and in the test dataset was 0.757 ± 0.006 and 0.764 ± 0.009, respectively. The time-AUCs exceeded 0.8. The DCA curve showed that the nomogram has better clinical value than the TNM staging system. Conclusions: Our study summarized the clinical characteristics and survival probability of LCLC patients, and a visual nomogram was developed to predict the 1-year, 3-year and 5-year OS of LCLC patients. This provides more accurate OS assessments for LCLC patients and helps clinicians make personal management decisions.

PD-1+ mast cell enhanced by PD-1 blocking therapy associated with resistance to immunotherapy.

BACKGROUND: Programmed cell death protein 1 (PD-1) antibody has been approved for a variety of tumors, but its effective rate is unsatisfactory. New evidence suggests that mast cells are an important component of the tumor microenvironment and are associated with resistance to immunotherapy, but the underlying mechanism is not clear. METHODS: Bioinformatics analysis of patients with melanoma in TCGA-SKCM and GSE91061 was used to determine the prognostic value of mast cells and their association with anti-PD-1 immunotherapy. HMC-1 cells (mast cell line) and bone marrow-derived mast cells (BMMCs) were used to verify the effect of PD-1 antibody and cromolyn sodium in vitro. The mouse subcutaneous melanoma model was used to verify the effect of the PD-1 antibody on mast cells in vivo. RESULTS: Bioinformatics analysis showed that mast cells were a poor prognostic factor associated with resistance to anti-PD-1 immunotherapy. PD-1 was expressed on the mast cell membrane. The PD-1 antibody promoted the release of histamine and cytokines from mast cells via the PI3K/AKT pathway and calcium signaling pathway. The activation of mast cells induced by PD-1 antibody could be partially inhibited by cromolyn sodium. In vivo, cromolyn sodium increased the efficacy of PD-1 antibody and decreased the infiltration of mast cells and the density of microvessels. CONCLUSION: PD-1+ mast cell activated by PD-1 antibody plays a negative role in the tumor microenvironment via the enhanced function of releasing histamine and cytokines. Inhibition of mast cell may provide a new solution to solve the low response rate of anti-PD-1 immunotherapy.

Metformin Improves Burn Wound Healing by Modulating Microenvironmental Fibroblasts and Macrophages.

Metformin, a biguanide, exerts different functions through various signaling pathways. In order to investigate the function and mechanism of metformin in burn wounds, we established burn rat models, subcutaneously injected metformin to treat the wounds, and observed the morphologies and the expression of collagen I, collagen III, fibronectin, and pro-inflammatory markers. In vitro experiments were performed to investigate the effects of metformin on the proliferation, migration, and collagen I synthesis of the mouse embryonic fibroblast (NIH 3T3) cell line and on the proliferation, apoptosis, and immune response of the mouse mononuclear macrophage (RAW 264.7) cell line. Finally, we studied the regulatory effects of metformin on a co-culture of RAW 264.7/NIH 3T3 cells. We found that 100 mM of metformin reduced dermal thickness, collagen I deposition, and mRNA expression of IL1ß and CCL2 in rat burn wounds. In vitro experiments revealed that metformin inhibited the proliferation of NIH 3T3 and RAW 264.7 cells. Metformin attenuated NIH 3T3 cell migration via the AMPK/mTOR pathway and attenuated collagen I synthesis through the TGFß1/Smad3 pathway. Metformin inhibited the apoptosis of RAW 264.7 cells induced by 10 µg/mL LPS. Metformin downregulated the mRNA expression of IL1ß and CCL2 in RAW 264.7 cells under 1 µg/mL LPS induction by inhibiting NF-κB p65 phosphorylation. In a RAW 264.7/NIH 3T3 co-culture, metformin attenuated collagen I synthesis in NIH 3T3 cells by inhibiting RAW 264.7 paracrine secretion of TGF-ß1. This provides new evidence related to the development of metformin for potentially improving burn wound healing.

Molecular characteristics of pediatric nasopharyngeal carcinoma using whole-exome sequencing.

OBJECTIVES: While a number of genetic and epigenetic events contributing to adult nasopharyngeal carcinomas (aNPC) development has been established, the scarcity of pediatric nasopharyngeal carcinoma (pNPC) hinders the understanding of the biology of the disease and rational treatment approach. We aim to identify the molecular characteristics of pNPC. MATERIALS AND METHODS: pNPC primary tumors with paired blood samples were collected and sequenced using whole-exome sequencing. Samples were collected from four tertiary academic medical centers in China. A total of 30 patients (25 male and 5 female) with pathologically confirmed NPC under the age of 20 were enrolled. RESULTS: Several genes such as C9orf84 (20 %), ZFHX4 (16.7 %), ZC3H6 (16.7 %), RBM38 (16.7 %) were frequently mutated in pNPC. Copy number analysis revealed highly recurring gain/amplification of the HLA class II genes at 6p21.32 (63.3 %) and losses of TOLLIP at 11p15.5 (20 %). Recurrent NUTM1 (16.7 %) fusion variants were found for the first time with pNPC. We also investigated germline genomic signatures and showed 8 of 30 (26.7 %) of the pNPC patients carrying germline pathogenic and/or likely pathogenic variants in known cancer-predisposing genes. Multi-dimensional comparison suggested that pNPC might exhibit distinct genomic profile compared to aNPC. In addition, pNPC exhibited significantly elevated level of PD-L1 expression than aNPC (percent of patients with >50 % PD-L1 expression: 92.0 % vs 32.1 %), suggesting high possibility of benefit from immunotherapy. CONCLUSION: Our results provide the first insight into the molecular basis of pNPC, and might offer novel targets and therapeutic approaches such as immunotherapy for this rare disease.

Imaging Signs for Determining Surgery Timing of Acute Intestinal Obstruction.

We aimed to analyze the computed tomography (CT) imaging signs of bowel wall ischemia in patients with acute intestinal obstruction and construct an imaging prediction model to guide clinical treatment. The CT imaging signs of patients with acute intestinal obstruction diagnosed in our center in recent 6 years were collected for retrospective analysis. The etiology of intestinal obstruction and incidence rate of bowel wall ischemia were recorded, and the specific CT findings of bowel wall ischemia, including mesenteric edema, bowel wall thickening, and fish tooth sign, were analyzed. Among the 302 patients selected, 130 surgically treated patients were eligible for analysis. Bowel wall ischemia in acute intestinal obstruction showed an incidence rate of 14.90%, and the incidence rates of bowel wall ischemia in intra-abdominal hernia, intussusception, incarcerated external abdominal hernia, and volvulus were about 92.30%, 50%, 35.71%, 33.33%, and 12.59%, respectively. The incidence rate of bowel wall ischemia in simple adhesive intestinal obstruction was about 12.59%, and that in malignancy-induced intestinal obstruction was about 6.56%. Univariate analysis revealed 5 factors with statistical significance, including bowel wall thickening, mesenteric edema, bowel wall pneumatosis, ascites, and fish tooth sign. Multivariate logistic regression analysis indicated that fish tooth sign, bowel wall thickening, and mesenteric edema were able to predict bowel wall ischemia, and the corresponding partial regression coefficients were 2.164, 1.129, and 1.173, odds ratios (ORs) were 8.707, 3.093, and 3.232, sensitivity was 0.356, 0.400, and 0.844, and specificity was 0.859, 0.835, and 0.529, respectively. Imaging signs of bowel wall thickening, mesenteric edema, and fish tooth sign are valuable in predicting bowel wall ischemia, among which bowel wall thickening and mesenteric edema have relatively high specificity and fish tooth sign has a relatively high sensitivity. Furthermore, a fish tooth sign has the most favorable predictive value for bowel wall ischemia in acute intestinal obstruction, followed by bowel wall thickening and mesenteric edema.

Neoadjuvant Chemoimmunotherapy for the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Clinical Trial.

PURPOSE: This study aimed to assess the antitumor activity and safety of neoadjuvant chemotherapy combined with PD-1 inhibitor camrelizumab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: In this single-center, single-arm, phase 2 trial, patients with resectable stage III-IVB HNSCC received chemotherapy [albumin-bound paclitaxel 260 mg/m2 (or docetaxel 75 mg/m2) plus cisplatin 75 mg/m2] and camrelizumab 200 mg on day 1 of each 21-day cycle for three cycles, followed by surgery, and adjuvant radiotherapy. Co-primary end points were pathological complete response (pCR) rate and safety. RESULTS: Thirty patients were enrolled and completed the neoadjuvant therapy, with an objective response rate (ORR) of 96.7% (29/30). Twenty-seven patients underwent surgery without delay, with an R0 resection rate of 92.6% (25/27). The clinical to pathological downstaging rate was 100% (27/27). The pCR rate was 37.0% [95% confidence interval (CI), 19.4%-57.6%], and the major pathological response (MPR) rate was 74.1% (95% CI, 53.7%-88.9%). The median follow-up duration was 16.1 months (range, 8.3-28.5), and the disease-free survival rate at 12 months was 95.8% (95% CI, 73.9%-99.4%). Grade 3 neoadjuvant therapy-related adverse events included rash (1; 3.3%), pruritis (1; 3.3%), and thrombocytopenia (1; 3.3%), and no grade 4 or 5 treatment-related events occurred. The most common surgical complication was delayed wound healing (5; 18.5%). CONCLUSIONS: Neoadjuvant chemotherapy plus camrelizumab for locally advanced HNSCC showed high ORR, pCR, and MPR rates, with an acceptable safety profile. These data support further evaluation of neoadjuvant chemoimmunotherapy for the treatment of locally advanced HNSCC.

A Bayesian network meta-analysis of the primary definitive therapies for locoregionally advanced nasopharyngeal carcinoma: IC+CCRT, CCRT+AC, and CCRT alone.

BACKGROUND: The major aim of this Bayesian network analysis was to determine the optimal treatment strategy for locoregionally advanced nasopharyngeal carcinoma (LANPC). METHOD: We systematically searched databases and extracted data from randomized clinical trials involving LANPC patients randomly assigned to receive induction chemotherapy followed by concurrent chemoradiotherapy (IC+CCRT), CCRT followed by adjuvant chemotherapy (CCRT+AC), or CCRT. RESULTS: In the network analysis, IC+CCRT was significantly better than CCRT alone for 5-year FFS (odds ratio [OR]: 1.63, 95% credible interval [CrI] 1.16-2.29), DMFS (OR: 1.56, 95% CrI 1.08-2.22), and LFRS (OR: 1.62, 95% CrI 1.02-2.59), but not OS (OR: 1.35, 95% CrI 0.92-2.00). Rank probabilities showed that IC+CCRT was ranked the best followed by CCRT+AC and CCRT for all 5-year outcomes. Although compared to IC+CCRT and CCRT, CCRT+AC did not significantly improve survival but had the highest 5-year survival rates. CONCLUSIONS: IC+CCRT could be recommended as a front-preferred primary definitive therapy for patients with LANPC.

Tumor factors associated with in-field failure for nasopharyngeal carcinoma after intensity-modulated radiotherapy.

BACKGROUND: To identify the tumor factors of in-field failure for nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. METHODS: Patterns of recurrence were classified as in-field, marginal, and out-field failures. Multivariate analyses with the Cox proportional hazards model were used to identify tumor-related factors of in-field failure. RESULTS: A total of 1039 patients with NPC received IMRT from 2012 to 2019 and 75 developed recurrences, with 88.0% (66/75) considered as having in-field failures. Multivariate analysis showed that pretreatment gross tumor volume of nasopharynx ≥68.8 mL and histopathological type of nonkeratinizing differentiated carcinoma (NKDC) were the independent tumor factors of in-field local failure, while gross tumor volume of involved lymph nodes ≥19.9 mL and cervical nodal necrosis (CNN) were associated with in-field regional failure (all p < 0.05). CONCLUSIONS: In-field failure was the major pattern of recurrence in patients with NPC. Large tumor volume, NKDC, and CNN were the tumor factors associated with in-field failure.

Evaluation of Minimal Change Lesions Using Linked Color Imaging in Patients With Nonerosive Reflux Esophagitis.

BACKGROUND AND AIMS: High prevalence of minimal change lesion (MCL) in nonerosive reflux esophagitis (NERD) patients is commonly recognized by many endoscopists. However, it is difficult to detect MCL with conventional white-light imaging (WLI) endoscopy. Linked color imaging (LCI), a novel image-enhanced endoscopy technology with strong, unique color enhancement, is used for easy recognition of early gastric cancer and detection of Helicobacter pylori infection. The aim of the study was to compare the efficacy of LCI and WLI endoscopy in evaluating MCL in patients with NER. MATERIALS AND METHODS: Forty-one patients with NERD and 38 subjects with nongastroesophageal reflux disease (non-GERD) were recruited in this study between August 2017 and July 2018. During upper gastrointestinal endoscopy, the distal 5 cm of the esophageal mucosal morphology at the squamocolumnar junction was visualized using WLI followed by LCI. MCL was defined as areas of erythema, blurring of the Z-line, friability, decreased vascularity, white turbid discoloration, and edema or accentuation of the mucosal folds. Three experienced endoscopists evaluated the color patterns for MCL on WLI images and on WLI combined with LCI images in both groups. A biopsy was taken 2 cm above the esophagogastric junction. Histologic slides were scored by a pathologist in a blinded manner. RESULTS: The proportion of MCL was higher in the patients with NERD (70.7%, 29/41) than in patients with non-GERD (39.5%, 15/38) using WLI combined with LCI. In 12 patients with NERD, both WLI and LCI showed normal mucosa. The MCL detection rate was significantly higher when using WLI combined with LCI than when using WLI (70.7% vs. 51.2%, P=0.039) in patients with NERD. The histopathologic score of MCL (+) was significantly higher than that of MCL (-) patients in both the NERD group (4.59±0.32 vs. 2.36±0.34, P<0.01) and the non-GERD group (3.47±0.50 vs. 2.00±0.28, P<0.01). The intraobserver reproducibility levels and interobserver agreement were better with LCI than with WLI alone. CONCLUSIONS: Frequency of MCL was higher in patients with NERD than in those with non-GERD. MCL can be identified by using WLI combined with LCI in patients with NERD. By enhancing endoscopic images, LCI is more sensitive in detecting MCL compared with WLI.

Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma.

The incidence of head and neck squamous cell carcinoma (HNSC) is increasing year by year. The nerve is an important component of the tumor microenvironment, which has a wide range of cross-talk with tumor cells and immune cells, especially in highly innervated organs, such as head and neck cancer and pancreatic cancer. However, the role of cancer-nerve cross-talk-related genes (NCCGs) in HNSC is unclear. In our study, we constructed a prognostic model based on genes with prognostic value in NCCGs. We used Pearson's correlation to analyze the relationship between NCCGs and immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. We used single-cell sequencing data to analyze the expression of genes associated with stage in different cells and explored the possible pathways affected by these genes via gene set enrichment analysis. In the TCGA-HNSC cohort, a total of 23 genes were up- or downregulated compared with normal tissues. GO and KEGG pathway analysis suggested that NCCGs are mainly concentrated in membrane potential regulation, chemical synapse, axon formation, and neuroreceptor-ligand interaction. Ten genes were identified as prognosis genes by Kaplan-Meier plotter and used as candidate genes for LASSO regression. We constructed a seven-gene prognostic model (NTRK1, L1CAM, GRIN3A, CHRNA5, CHRNA6, CHRNB4, CHRND). The model could effectively predict the 1-, 3-, and 5-year survival rates in the TCGA-HNSC cohort, and the effectiveness of the model was verified by external test data. The genes included in the model were significantly correlated with immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. Single-cell sequencing data of HNSC showed that CHRNB4 was mainly expressed in tumor cells, and multiple metabolic pathways were enriched in high CHRNB4 expression tumor cells. In summary, we used comprehensive bioinformatics analysis to construct a prognostic gene model and revealed the potential of NCCGs as therapeutic targets and prognostic biomarkers in HNSC.

Comparison of TPF and TP Induction Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma Based on TNM Stage and Pretreatment Systemic Immune-Inflammation Index.

PURPOSE: To evaluate the efficacy and toxicity of the two IC (induction chemotherapy) regimens, TPF (taxanes, cisplatin, and 5-fluorouracil) and TP (taxanes and cisplatin) combined with concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients. METHODS: Ultimately, we enrolled 213 patients at stage III-IVA in this retrospective study. The prognosis of TPF and TP was compared by Kaplan-Meier and Cox proportional hazard regression. The toxicities were evaluated according to CTCAE v4.0 and RTOG criteria. RESULTS: TPF was found to have a higher 5-year DMFS in stage IVA and N2-3 patients. The optimal value of pretreatment SII was 432.48. A further subgroup analysis revealed that patients in stage IVA combined with SII ≥432.48 showed superior OS (P=0.038) and DMFS (P=0.028) from TPF. Also, SII was proved to be a prognostic element for PFS (HR 2.801, P=0.018) and DMFS (HR 3.735, P=0.032) in multivariate analysis, and IC regimen (HR 2.182, P=0.049) for predicting DMFS. The rate of grade 3-4 leukopenia (P=0.038), neutropenia (P=0.021), radiation oral mucositis (P=0.048), diarrhea (P=0.036), and ear damage (P=0.046) were more common in TPF group. CONCLUSION: Our study revealed that TPF regimen showed a higher 5-year DMFS for stage IVA and N2-3 patients, while for stage III and N0-1, TP might be ample. In high-risk LA-NPC patients (stage IVA combined with pretreatment SII ≥432.48), TPF had a higher 5-year OS and DMFS, with more grade 3-4 toxicities, but most of them were endurable.