Phase 2 trial of neoadjuvant toripalimab with chemotherapy for resectable stage III non-small-cell lung cancer.

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).

The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors.

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 < 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (p = 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.

Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection.

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.

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3ß signalling pathway in renal cell carcinoma.

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/GSK3ß signalling pathway in RCC, AGK can increase nuclear accumulation of ß-catenin, which further upregulated TCF/LEF transcription factor activity. CONCLUSIONS: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3ß signalling pathway and might be a potential target for the further research of RCC.

Comparative phylogeography of two monogenean species (Mazocraeidae) on the host of chub mackerel, Scomber japonicus, along the coast of China.

In the present paper, the phylogeographies of two monogenean species, Pseudokuhnia minor and Kuhnia scombri, on the same species of host, Scomber japonicus, were studied. Fragments of the mitochondrial cytochrome c oxidase subunit 1 gene were sequenced for 264 individuals of P. minor and 224 individuals of K. scombri collected from 10 localities along the coast of China. Genetic diversity of K. scombri was higher than that of P. minor, which may imply that P. minor has a lower evolution rate and/or is a younger species. The neighbour-joining (NJ) trees of both parasites were comprised of two clades without association to sample sites, which is the signature of remixing populations following past division. Analyses of molecular variance and pairwise fixation index revealed different genetic structures for the populations of these two closely related species along the coast of China: P. minor without significant genetic structure, while K. scombri has some genetic differentiation. Both neutrality tests and mismatch distribution suggested that the populations of these two species of parasites experienced population expansion in the late Pleistocene era due to the glacial-interglacial cycles induced by climatic oscillations.

Complete mitochondrial genome of the pelagic stingray Pteroplatytrygon violacea (Myliobatiformes: Dasyatidae).

The pelagic stingray Pteroplatytrygon violacea is the only pelagic species of the Dasyatidae (Chondrichthyes: Elasmobranchii), which is widely distributed in all tropical, subtropical and temperate oceans. In this study, the complete mitochondrial genome of Pteroplatytrygon violacea was determined. It is 17,665 bp in length and contains 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 control region, with the typical gene order and direction of transcription of vertebrates. The overall nucleotide compositions of the whole mitogenome are 30.8% A, 26.9% C, 28.6% T and 13.7% G. The ND2 and CO1 sequences are highly similar to the corresponding sequences of this species available in NCBI collected from the Atlantic sea.

Underlying mechanisms of Tai-Chi-Chuan training for improving balance ability in the elders.

OBJECTIVE: To compare balance ability between elderly individuals who practiced Tai-Chi-Chuan (TCC) for average 9.64 years and elderly individuals who did not practice TCC and its relationship with lower extremity muscle strength and ankle proprioception. METHODS: Twenty-five elderly volunteers were divided into two groups according to their TCC practcing experience. Sixteen were TCC group and the other nine were control population. Subjects completed a static balance test and ankle proprioception test using a custom-designed evaluation system, and concentric and eccentric knee extensor and flexor muscle strength tests. Subjects stood on the plate form to measure the proprioception in functional standing position which was differed from the previous studies. Multiple linear regressions were also used to predict the important factor affecting balance. RESULTS: TCC group performed better than the control group in balance, proprioception, and muscle strength of lower extremity. The proprioception was the most important factor related to balance ability and it can be accounted for explaining 44% of variance in medial-lateral sway direction, and 53% of variance in antero-posterior sway direction. The proprioception may be a more important factor which affecting the balance ability. CONCLUSION: TCC training is recommended to the elders; as it can improve balance ability through better proprioception.

Potential risk of malposition of nasogastric tube using nose-ear-xiphoid measurement.

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.

Feasibility of a novel two-piece nasogastric feeding tube for patients with dysphagia.

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.

Relationship between severity of shoulder subluxation and soft-tissue injury in hemiplegic stroke patients.

OBJECTIVE: The aims of this study were: (i) to determine whether the severity of post-hemiplegic shoulder subluxation in stroke patients correlates with soft-tissue injury; and (ii) to determine the shoulder subluxation measurement cut-off points that are indications for further ultrasound examination for soft-tissue injuries in these patients. DESIGN: Cross-sectional study. PATIENTS: A total of 39 stroke patients with shoulder subluxation. METHODS: Shoulder subluxation was evaluated by physical examination, radiography and ultrasound. Soft-tissue injuries were assessed by ultrasound. Subluxation parameters were entered into stepwise logistic regression analyses to predict biceps and supraspinatus tendonitis. With the assumption that shoulder subluxation can be a predisposing factor for tendonitis, receiver operating characteristic curves for shoulder subluxation parameters of the affected side were used to determine cut-off points for optimal sensitivity and specificity of biceps and supraspinatus tendonitis. RESULTS: Shoulder subluxation lateral distance, measured by physical examination, is a predictor for supraspinatus tendonitis (odds ratio = 34.9, p = 0.036). Further ultrasound investigation for soft-tissue injury is indicated when subluxation lateral distance, measured by physical examination is ≥ 2.25 cm or, measured by radiographic examination, ≥ 3.18 cm for lateral distance, ≥ 3.08 cm for vertical distance, or ≥ 2.65 cm for horizontal distance. CONCLUSION: When post-hemiplegic shoulder subluxation measurements exceed the above-mentioned cut-off points in physical or radiographic examinations, further ultrasound evaluation for soft-tissue injury is recommended.

Ultrasonographic findings in hemiplegic knees of stroke patients.

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.