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Abstract A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p

Abstract Background Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6–12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. Methods AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. Results AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. Conclusions AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

Multimodality treatment provides modest survival benefits for patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC). Nevertheless, preoperative immunotherapy has continuously been shown to be promising in treating resectable NSCLC.This phase 2 trial enrolled patients with AJCC-defined stage IIIA or T3-4N2 IIIB NSCLC deemed surgically resectable. Patients received three cycles of neoadjuvant treatment with intravenous PD-1 inhibitor toripalimab (240 mg), carboplatin (area under the curve 5), and pemetrexed (500 mg/m2 for adenocarcinoma) or nab-paclitaxel (260 mg/m2 for other subtypes) on day 1 of each 21-day cycle. Surgical resection was performed 4–5 weeks afterward. The primary endpoint was major pathological response (MPR), defined as less than 10% residual tumor remaining at the time of surgery.Thirty-three patients were enrolled, of whom 13 (39.4%) had T3-4N2 stage IIIB disease. Thirty (90.9%) patients underwent resection and all except one (96.7%) achieved R0 resection. Twenty patients (60.6%) in the intention-to-treat population achieved an MPR, including 15 patients (45.5%) who achieved a pathological complete response (pCR). The MPR and pCR rates in the per-protocol population were 66.7% and 50.0%, respectively. The surgical complications included three cases of arrhythmias, one case of a prolonged air leak, and one case of chylothorax. The most common grade 3 treatment-related adverse event (TRAE) was anemia (2, [6.1%]). Severe TRAEs included one (3.0%) case of grade 3 peripheral neuropathy that resulted in surgical cancellation.Toripalimab plus platinum-based doublet chemotherapy yields a high MPR rate, manageable toxicity, and feasible resection in stage III NSCLC.Trial ClinicalTrials.gov (NCT04304248)

Adjuvant chemotherapy after surgery is the standard treatment modality for stage III and part of stage II or stage IV colorectal cancer (CRC) patients. However, the 5-year overall survival (OS) rate remains unsatisfactory. Thus, developing combination therapies is essential to improve the prognosis of patients with CRC. The present study aimed to determine the effect of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with CRC. 122 patients with CRC treated with postoperative adjuvant chemotherapy were retrospectively included in this study. Among them, 62 patients received adjuvant chemotherapy only (control group), while the other 60 patients, with similar demographic and clinical characteristics, received adjuvant chemotherapy and sequential CIK cell immunotherapy (CIK group). Survival analysis showed significantly improved disease free survival (DFS) and OS rates in the CIK group compared with the control group (log-rank test, P = .0024; P = .008, respectively). Univariate and multivariate analyses indicated that sequential CIK cell treatment was an independent prognostic factor for patients’ DFS and OS. Subgroup analyses showed that sequential CIK cell treatment significantly improved the DFS and OS of patients with high-risk T4 stage and insufficient chemotherapy duration. In conclusion, these data indicate that sequential adjuvant CIK cell treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with CRC, particularly for patients with high-risk T4 stage and insufficient chemotherapy duration.

This study investigated satellite cells and their related molecular events adapted to light moderate endurance training in the white gastrocnemius muscle of the rat. The white gastrocnemius muscle of male Sprague-Dawley rats that had been trained for 4 weeks and 8 weeks, with control rats being analysed alongside them, was selected for analysis (n=3 per group). The training protocol consisted of treadmill running at 20 m · min-1 for 30 min on a 0% grade, for 3 days · week-1. Immunohistochemical staining coupled with image analysis was used for quantification. To provide deeper insight into the cell layer, 40 sections per rat, corresponding to 120 values per group, were obtained as a mean value for statistical comparison. The results indicated that at week 4, training effects increased the vascular endothelial growth factor (VEGF) content and c-met positive satellite cell numbers. At week 8, the training effect was attenuated for VEGF and c-met satellite cell numbers, but it increased in the muscle fibre area. Additionally, c-met positive satellite cell numbers correlated with VEGF content (r = 0.79, p

Clinical and radiologic asymmetric arthritic differences between paralyzed and nonparalyzed limbs of stroke patients have been reported. Arthritic pathology aggravates motor dysfunction and compromises rehabilitation. Musculoskeletal ultrasonography plays an important role in showing soft tissue and the articular cartilage of the knee. Fifty-nine patients with either ischemic or hemorrhagic stroke-induced right or left hemiplegia were recruited to evaluate soft-tissue and intra-articular cartilage changes in hemiplegic knees of stroke patients using ultrasonography. An additional 15 subjects (30 knees) without knee disease or a history of knee trauma or surgery were used as controls. There were significant differences in suprapatellar effusion and patellar tendinitis between hemiplegic and nonhemiplegic knees. Suprapatellar effusion and pes anserinus tendinitis were correlated with Brunnstrom stage. The length of time since stroke onset was not significantly correlated with positive ultrasonographic findings in hemiplegic knees. In conclusion, ultrasonography is useful for detecting periarticular soft-tissue changes and intra-articular lesions in hemiplegic knees of stroke patients.

BACKGROUND: Correct placement of nasogastric tubes provide proper functionality and maximize benefit and minimize risk. The Nose-Ear-Xiphoid (NEX) body surface estimate method is a long-lasting technique, and this study was conducted to evaluate the correlation between NEX method and the secure insertion depth of nasogastric tube. MATERIALS AND METHODS: Thirty patients with nasogastric tube insertion who received whole body positron emission tomography with computerized tomography scan (PET-CT) were recruited. All data were gathered in the image center, which included Nose-Ear (NE), Ear-Xiphoid (EX), Nose-Ear-Xiphoid (NEX), glabella-xiphoid (GX) and glabella-umbilicus (GU) lengths. The distances of the inserted portion of the nasogastric tube between the cardiac and the nostril were measured by multiplanar reconstruction algorithm. RESULTS: Only one patient successfully placed all side-holes into the stomach while using NEX method to estimate inserting depth. Twenty-nine patients (96.7%) failed to place correctly. Fourteen participants had one or more side-holes in both the esophagus and the stomach sides. Fifteen patients could not pass through any side-hole across the gastroesophageal junction. They had shorter EX distances (p = 0.02), but no difference among the NE distances. Body height had the highest statistical correlation with nasogastric tube length (adjusted R(2) = 0.459), as compared with the NEX, GX and GU body surface methods. CONCLUSION: This study suggests that NEX method is inappropriate for adult patients to estimate the ideal inserting length of nasogastric tube. Physicians should realize these underinsertions with any side-hole above the gastroesophageal junctions may increase the potential risk of complications.

Introduction The exposed section of a traditional nasogastric (NG) tube can interfere with patients' social activities and thereby result in distress. This study was conducted to evaluate the feasibility and safety of a novel two-piece NG tube for patients with dysphagia. Methods Ten patients with dysphagia were recruited between November 2011 and May 2012. Patients who were unconscious or in critical condition, had a traditional NG tube < 50 cm or > 60 cm in fixed length, or were unable to follow instructions or sign consent forms were excluded. The two-piece NG tube, which was placed in the patients for one week, comprised a removable external tube that can be joined to an internal tube via a T-connector, which was placed close to the naris. Events related to safety (e.g. nasal pressure sores, number of unplanned extubation, displacement and spontaneous migration of the NG tube, other unpredictable injuries) and effectiveness (e.g. liquid food spills, tube obstruction, perfusion rate, other adverse circumstances) were assessed daily. Results All patients received feeding without complication using the two-piece NG tube and none experienced premature removal of the tube. No serious NG tube complications or malfunctions were observed. Conclusion The results of this study indicate that the two-piece NG feeding tube is a feasible option for patients with dysphagia. Future improvements to the connector may help enhance its performance. A rigorous randomised controlled trial to examine the effects of the two-piece NG tube on patients' quality of life and quality of medical care is being planned. [ABSTRACT FROM AUTHOR]