Effects of a calorie-restricted dietary intervention on weight loss and gut microbiota diversity in obese patients with sleep deprivation.

OBJECTIVES: This study aimed to investigate the effects of a calorie-restricted dietary (CRD) intervention on weight and gut microbiota diversity in obese patients with sleep deprivation (SD). METHODS: Twenty obese patients were divided into a sleep deprivation group (SD group, n = 10) and a nonsleep deprivation group (NSD group, n = 10), both of which underwent a CRD intervention for 12 weeks. Measurement of anthropometric parameters, biochemical examinations and gut microbiota detection were performed at baseline and at the end of week 12. Mi Smart Bands 1 (Standard Option) were used to monitor sleep and exercise. RESULTS: (1) The CRD intervention improved body weight (BW), waist circumference (WC), blood pressure (BP), basal metabolic rate (BMR), body fat content (BFC), and insulin resistance index (HOMA-IR) in all obese patients. (2) In the NSD group, BW, BFC, VFA (visceral fat area), BMR and total cholesterol (TC) were significantly reduced after the CRD intervention (P < 0.05). (3) The alpha diversity of the gut microbiota remained unchanged after the intervention in the two groups. (4) There was a negative correlation between Mollicutes and BMR in the NSD group. CONCLUSIONS: The effects of a CRD intervention weaken on weight loss and the metabolism of blood lipids may be weakened by SD. The abundance of Mollicutes bacteria may be related to weight loss after a CRD intervention in obese patients. LEVEL OF EVIDENCE: III, prospective cohort study.

[Transurethral 180 W front-firing GreenLight laser vaporization of the prostate for the treatment of benign prostatic hyperplasia].

OBJECTIVE: To evaluate the clinical effect and safety of transurethral 180 W front-firing GreenLight laser vaporization of the prostate (PVP) in the treatment of benign prostatic hyperplasia (BPH). METHODS: A total of 61 BPH patients underwent 180W front-firing GreenLight laser PVP (n = 30, the PVP group) or transurethral plasmakinetic resection of the prostate (n = 31, the control group) from March to December 2019. We collected the pre-, intra- and post-operative clinical data and compared them between the two groups of patients. RESULTS: Operations were successfully completed in all the cases with no blood transfusion or serious complications. Compared with the controls, the patients of the PVP group showed remarkably less intra-operative blood loss (ï¼»62.3 ± 15.9ï¼½ vs ï¼»48.8 ± 9.6ï¼½ ml, P < 0.05), shorter operation time (ï¼»75.0 ± 9.9ï¼½ vs ï¼»57.5 ± 19.0ï¼½ min, P < 0.05), postoperative bladder lavage time (ï¼»64.4 ± 10.5ï¼½ vs ï¼»25.2 ± 11.5ï¼½ h, P < 0.05), catheter-indwelling time (ï¼»5.1 ± 0.5ï¼½ vs ï¼»2.5 ± 0.5ï¼½ d, P < 0.05) and hospitalization time (ï¼»7.3 ± 1.7ï¼½ vs ï¼»4.1 ± 0.6ï¼½ d, P < 0.05), and a lower incidence of postoperative hematuria (12.9% ï¼»4/31ï¼½ vs 0% ï¼»0/30ï¼½, P < 0.05). No statistically significant differences, however, were found between the two groups in the incidence rates of capsular perforation, transurethral resection syndrome (TURS), urinary incontinence, urethral stricture and post-extubation urinary retention. Significant improvement was observed in IPSS, QOL, Qmax and PVR in both groups post-operatively (P < 0.05). CONCLUSIONS: Compared with transurethral plasmakinetic resection of the prostate, 180W front-firing GreenLight laser PVP, with the advantages of less bleeding, shorter catheter-indwelling time and faster recovery, is safer and more effective for the treatment of BPH, with no need for drug withdrawal for those taking anticoagulants, and especially applicable to the elderly and high-risk patients.

FGFR2 Promotes Gastric Cancer Progression by Inhibiting the Expression of Thrombospondin4 via PI3K-Akt-Mtor Pathway.

BACKGROUND/AIMS: Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC. METHODS: Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model. RESULTS: FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis. CONCLUSION: The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2.

Effects of different treatment modalities on cardiovascular disease in ARR-positive hypertensive patients.

Data on the prognosis of clinically undiagnosed hypertensive patients who are aldosterone-to-renin ratio (ARR) positive are still scarce. Therefore, we investigated the clinical characteristics of clinically undiagnosed hypertensive patients who were ARR-positive and the influence of their different treatments on the occurrence and development of complications. A total of 285 hypertensive patients data with ARR ≥ 3.8 in the Second People's Hospital of Huai'an from January 2019 to December 2021 were collected, and 135 undiagnosed hypertensive patients were ultimately included in the analysis. According to their treatment strategy in various clinical departments, 135 patients were divided into the operation, spironolactone and control groups. Then, the clinical characteristics and the occurrence and development of complications in the three groups were compared. The results suggested that: (1) Only 34 (11.9%) of 285 hypertensive patients with ARR ≥ 3.8 were clearly diagnosed with Primary aldosteronism (PA) through functional tests, and the blood pressure (BP) compliance rate was only 50.30% during follow-up. (2) Based on exclusion criteria, 135 undiagnosed hypertensive patients were eventually included in the analysis. Patients in the surgery group had lower blood potassium levels and higher aldosterone levels than those in the other two groups, and their risk of new cerebrovascular complications was lower than that of the patients in the spironolactone group. (3) The risk of new cerebrovascular complications in the spironolactone group was 9.520 times higher than that of the control group, and this risk mainly occurred in patients with ARR values of 3.8-5.7. On the whole, surgery remains a good option for hypertensive patients with severe hyperaldosteronism and hypokalemia and those unable to undergo confirmatory tests; however, spironolactone therapy in patients with clinically undiagnosed hypertension, especially those with 3.8 ≤ ARR < 5.7, confered a higher risk of new cerebrovascular complications.

Case report: Case report and literature review: Treatment of sweat gland carcinoma.

Background: Sweat gland carcinoma (SGC) is a rare neoplasm originating from sweat glands. Surgical resection is the first choice for SGC treatment, and there is no consensus on other treatments for advanced SGC. Methods and result: In this case report, we present a case of a female patient with advanced SGC who received surgery; radiotherapy; multiple lines of chemotherapy, which include docetaxel, nedaplatin, albumin-bound paclitaxel, and pemetrexed; and immunotherapy (camrelizumab). The survival time of this patient is 35 months. MRI tumor monitoring indicated that these treatments slowed the progression of the disease. The effectiveness of chemotherapy, radiotherapy, and immunotherapy should be tested for more patients with SGC in the future. Conclusion: Although the patient's tumor was uncontrolled eventually, multiple treatments delayed tumor growth over a period of time, providing ideas for others when choosing regimens.

A contrast-enhanced CT-based whole-spleen radiomics signature for early prediction of oxaliplatin-related thrombocytopenia in patients with gastrointestinal malignancies: a retrospective study.

Background: Thrombocytopenia is a common adverse event of oxaliplatin-based chemotherapy. Grade 2 or higher oxaliplatin-related thrombocytopenia may result in dose reduction, discontinuation or delay initiation of chemotherapy and may adversely affect the therapeutic efficacy and even overall survival of patients. Early recognition of patients at risk of developing grade 2 or higher thrombocytopenia is critical. However, to date there is no well-established method to early identify patients at high risk. The aims of this study were to develop and validate a contrast-enhanced CT-based whole-spleen radiomics signature for early prediction of grade 2 or higher thrombocytopenia in patients with gastrointestinal malignancies treated with oxaliplatin-based chemotherapy and to explore the incremental value of combining the radiomics signature and conventional clinical factors for risk prediction. Methods: A total of 119 patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy from March 2017 to December 2020 were retrospectively included and randomly divided into a training cohort (n = 85) and a validation cohort (n = 34). Grade 2 or higher thrombocytopenia occurred in 26.1% of patients (22 and nine patients in the training and validation cohort, respectively) with a median time interval of 101 days from the start of chemotherapy. The whole-spleen radiomics features were extracted on the portal venous phase of the first follow-up CT images. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to select radiomics features and to build the radiomics signature for the prediction of grade 2 or higher thrombocytopenia. A clinical model that included clinical factors only and a clinical-radiomics model that incorporated clinical factors and radiomics signature were constructed. The performances of both models were evaluated and compared in the training, validation and the whole cohorts. Results: The radiomics signature yielded favorable performance in predicting grade 2 or higher thrombocytopenia, with the area under the curve (AUC), sensitivity and specificity being 0.865, 81.8% and 84.1% in the training cohort and 0.747, 77.8% and 80.0% in the validation cohort. The AUCs of the clinical-radiomics model in the training and validation cohorts reached 0.913 (95% CI [0.720-0.935]) and 0.867 (95% CI [0.727-1.000]), greater than the AUCs of the clinical model. Integrated discrimination improvement (IDI) index showed that incorporating radiomic signature into conventional clinical factors significantly improved the predictive accuracy by 17.0% (95% CI [4.9%-29.1%], p = 0.006) in the whole cohort. Conclusions: Contrast-enhanced CT-based whole-spleen radiomics signature might serve as an early predictor for grade 2 or higher thrombocytopenia during oxaliplatin-based chemotherapy in patients with gastrointestinal malignancies and provide incremental value over conventional clinical factors.

FGFR2 upregulates PAI-1 via JAK2/STAT3 signaling to induce M2 polarization of macrophages in colorectal cancer.

Fibroblast growth factor receptor 2 (FGFR2) is frequently activated by overexpression or mutation, and an abnormal fibroblast growth factor (FGF)/FGFR signaling pathway is associated with the occurrence, development, and poor prognosis of colorectal cancer (CRC). Our preliminary analysis found that plasminogen activator inhibitor-1 (PAI-1) expression may be related to FGF/FGFR signaling, however, their role in the tumor immune microenvironment remains unclear. In this study, we observed markedly higher PAI-1 expression in CRC patients with poor survival rates. PAI-1 is regulated by FGF/FGFR2 in colon cancer cells and is involved in M2 macrophage polarization. Mechanistically, inhibiting the JAK2/STAT3 signaling pathway could cause PAI-1 downregulation. Furthermore, the activation of phosphorylated STAT3 upregulated PAI-1. In vivo, FGFR2 overexpression in tumor-bearing mouse models suggested that a PAI-1 inhibitor could rescue FGFR2/PAI-1 axis-induced M2 macrophage polarization, which leads to effective immune activity and tumor suppression. Moreover, the combination of a PAI-1 inhibitor and anti-PD-1 therapy exhibited superior antitumor activity in mice. These findings offer novel insights into the molecular mechanisms underlying tumor deterioration and provide potential therapeutic targets for CRC treatment.

Development and validation of a contrast-enhanced CT-based radiomics nomogram for preoperative diagnosis in neuroendocrine carcinoma of digestive system.

Objectives: To develop and validate a contrast-enhanced CT-based radiomics nomogram for the diagnosis of neuroendocrine carcinoma of the digestive system. Methods: The clinical data and contrast-enhanced CT images of 60 patients with pathologically confirmed neuroendocrine carcinoma of the digestive system and 60 patients with non-neuroendocrine carcinoma of the digestive system were retrospectively collected from August 2015 to December 2021 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and randomly divided into a training cohort (n=84) and a validation cohort (n=36). Clinical characteristics were analyzed by logistic regression and a clinical diagnosis model was developed. Radiomics signature were established by extracting radiomic features from contrast-enhanced CT images. Based on the radiomic signature and clinical characteristics, radiomic nomogram was developed. ROC curves and Delong's test were used to evaluate the diagnostic efficacy of the three models, calibration curves and application decision curves were used to analyze the accuracy and clinical application value of nomogram. Results: Logistic regression results showed that TNM stage (stage IV) (OR 6.8, 95% CI 1.320-43.164, p=0. 028) was an independent factor affecting the diagnosis for NECs of the digestive system, and a clinical model was constructed based on TNM stage (stage IV). The AUCs of the clinical model, radiomics signature, and radiomics nomogram for the diagnosis of NECs of the digestive system in the training, validation cohorts and pooled patients were 0.643, 0.893, 0.913; 0.722, 0.867, 0.932 and 0.667, 0.887, 0.917 respectively. The AUCs of radiomics signature and radiomics nomogram were higher than clinical model, with statistically significant difference (Z=4.46, 6.85, both p < 0.001); the AUC difference between radiomics signature and radiomics nomogram was not statistically significant (Z=1.63, p = 0.104). The results of the calibration curve showed favorable agreement between the predicted values of the nomogram and the pathological results, and the decision curve analysis indicated that the nomogram had favorable application in clinical practice. Conclusions: The nomogram constructed based on contrast-enhanced CT radiomics and clinical characteristics was able to effectively diagnose neuroendocrine carcinoma of the digestive system.

Revalidation of the ATTRACTION-4 study in a real-world setting: a multicenter, retrospective propensity score matching study in China.

Background: Immune-checkpoint inhibitors (ICIs) combined with chemotherapy have been successfully used in clinical trials to treat advanced gastric cancer. However, the efficacy and safety of first-line immunotherapy combined with chemotherapy in Chinese patients are unknown. Methods: This multicenter retrospective study included patients with human epidermal growth factor receptor-2 (HER-2) negative advanced gastric cancer treated with first-line chemotherapy or chemotherapy with an ICI between January 2019 and December 2022. Propensity score matching was used to compare progression-free survival (PFS), overall survival, objective response rates, and adverse reactions between cohorts. Results: After propensity score matching, 138 patients, who had balanced baseline characteristics, were included in the chemotherapy and combination treatment groups. The median follow-up duration was 16.90 months, and the median PFS was 8.53 months (95% confidence interval [CI] 7.77-9.28) in the combination treatment group and 5.97 months (95% CI 4.56-7.37) in the chemotherapy group. The median survival duration was 17.05 months (95% CI 14.18-19.92) in the combination treatment group and 16.46 months (95% CI 12.99-19.93) in the chemotherapy group. The PFS subgroup analysis revealed that age ≥65 years, women, Eastern Cooperative Oncology Group performance status of 1, non-signet ring cell carcinoma, esophagogastric junction, liver metastasis, peritoneal metastasis, no massive ascites, only one metastatic organ, and combined platinum-based chemotherapy correlated with treatment benefit. The incidences of adverse events above grade 3 were comparable between groups. Conclusions: Our study confirmed the ATTRACTION-4 trial results. Compared with chemotherapy, first-line ICIs combined with chemotherapy prolonged PFS but did not improve overall survival in patients with HER-2-negative advanced gastric cancer.

Efficacy and safety of low-dose apatinib plus S-1 versus regorafenib and fruquintinib for refractory metastatic colorectal cancer: a retrospective cohort study.

Background: At present, regorafenib and fruquintinib are the standard regimens for refractory metastatic colorectal cancer patients in China, but both options have limited efficacy. The aim of this study was to investigate the efficacy and safety of low-dose apatinib plus S-1 compared with regorafenib and fruquintinib in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies. Methods: The records of 114 patients with refractory mCRC in our center from April 2016 to September 2020 were retrospectively reviewed. Among these patients, 43 received apatinib 250 mg/day combined with S-1, 36 received regorafenib starting at 80 mg/day with weekly escalation, and 35 received fruquintinib 5 mg/day orally. Patients received radiographic examination every 1.5-2 months during the treatment period, progression-free survival time and overall survival time were analyzed and recorded. Results: The baseline clinical characteristics of the patients were broadly similar among the three groups. The median progression-free survival (mPFS) was 3.9 months [95% confidence interval (CI): 2.5-5.3] in the apatinib plus S-1 group, 3.1 months (95% CI: 1.9-4.2) in the fruquintinib group, and 2.4 months (95% CI: 2.1-2.7) in the regorafenib group, the mPFS of apatinib plus S-1 was significantly longer than that of regorafenib (HR =0.49, P=0.003) and fruquintinib (HR =0.60, P=0.048). The median overall survival (OS) was 8.2 months (95% CI: 5.4-11.0) in the apatinib plus S-1 group, 7.8 months (95% CI: 5.3-10.3) in the fruquintinib group, and 7.5 months (95% CI: 4.2-10.7) in the regorafenib group, which was comparable among the 3 groups. There was no statistical difference in disease control rate (DCR) among the three groups. Patients in the apatinib plus S-1 group had a higher incidence of hematological toxicity including anemia (62.8%), neutropenia (30.2%), and thrombocytopenia (39.5%), and the hand-foot skin reaction (58.3%) was more prevalent in the regorafenib group, while the adverse reaction of hypertension (45.7%) in the fruquintinib group was very significant. Conclusions: Low-dose apatinib plus S-1 prolonged PFS compared with regorafenib and fruquintinib, and is a potential alternative regimen for the treatment of refractory mCRC with tolerable and controlled toxicity.

Nab-paclitaxel plus S-1 versus oxaliplatin plus S-1 as first-line treatment in advanced gastric cancer: results of a multicenter, randomized, phase III trial (GAPSO study).

Background: This study aimed to investigate the superiority of nab-paclitaxel plus S-1 (AS) over oxaliplatin plus S-1 (SOX) in patients with advanced gastric cancer (AGC). Methods: In this multicenter, randomized, phase III superiority trial, eligible patients with unresectable, locally advanced gastric adenocarcinoma were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 260 mg/m2 on day 1 or 130 mg/m2 on days 1 and 8; oral S-1 40-60 mg twice daily for 14 days) or SOX (130 mg/m2 oxaliplatin on day 1; oral S-1 40-60 mg twice daily for 14 days) every 3 weeks for up to six cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival, objective response rate, and safety. Results: Owing to slow enrolment, an unplanned interim analysis was performed, resulting in the early termination of the study on 31 December 2021 (data cutoff). Between March 2019 and March 2021, 97 patients (AS, n = 48; SOX, n = 49) were treated and evaluated for efficacy and safety of AS and SOX. As of the data cutoff, the median follow-up was 23.13 months [95% confidence interval (CI), 13.39-32.87]. The median PFS was 9.03 months (95% CI, 6.50-11.56) in the AS group and 5.07 months (95% CI, 4.33-5.81) in the SOX group, demonstrating a better PFS tendency following AS treatment than SOX treatment (hazard ratio = 0.59; 95% CI, 0.37-0.94; p = 0.03). The most common grade 3 or worse adverse events were anemia, neutropenia, and leukopenia in both groups, with a higher incidence of thrombocytopenia in the SOX group. Conclusion: Although this study was terminated early, the results demonstrated a better PFS tendency in patients with AGC who were treated with AS than in those treated with SOX, with controllable toxicities. Trial registration: Clinical Trials.gov identifiers: NCT03801668. Registered January 11, 2019.

A Minibatch Proximal Stochastic Recursive Gradient Algorithm Using a Trust-Region-Like Scheme and Barzilai-Borwein Stepsizes.

We consider the problem of minimizing the sum of an average of a large number of smooth convex component functions and a possibly nonsmooth convex function that admits a simple proximal mapping. This class of problems arises frequently in machine learning, known as regularized empirical risk minimization (ERM). In this article, we propose mSRGTR-BB, a minibatch proximal stochastic recursive gradient algorithm, which employs a trust-region-like scheme to select stepsizes that are automatically computed by the Barzilai-Borwein method. We prove that mSRGTR-BB converges linearly in expectation for strongly and nonstrongly convex objective functions. With proper parameters, mSRGTR-BB enjoys a faster convergence rate than the state-of-the-art minibatch proximal variant of the semistochastic gradient method (mS2GD). Numerical experiments on standard data sets show that the performance of mSRGTR-BB is comparable to and sometimes even better than mS2GD with best-tuned stepsizes and is superior to some modern proximal stochastic gradient methods.

Pyrotinib enhances the radiosensitivity of HER2­overexpressing gastric and breast cancer cells.

The overexpression or amplification of HER2 has been observed in a significant proportion of both gastric cancer (GC) and breast cancer (BC) cases. Pyrotinib is an irreversible dual (EGFR/HER2) tyrosine kinase inhibitor (TKI), newly evaluated for the treatment of HER2­overexpressing cancer types. As radiotherapy (RT) serves a crucial role in controlling the local recurrence of GC and BC, the present study investigated the impact of pyrotinib on the irradiation response. The current results demonstrated that pyrotinib enhanced the radiosensitivity of HER2­overexpressing GC and BC cells in vitro and in vivo. In both NCI­N87 and SKBR3 cells, pyrotinib suppressed the irradiation­induced HER2 nuclear transport. Furthermore, pyrotinib increased DNA damage induced by irradiation in both cancer cell lines. Pyrotinib also enhanced the cytotoxicity of docetaxel, which may provide a novel strategy for potential drug combinations. Thus, pyrotinib is a promising irradiation sensitizer in patients with HER2­overexpressing GC and BC. The present results provide a theoretical foundation for further clinical evaluation of pyrotinib.

High pretreatment neutrophil-to-lymphocyte ratio as a predictor of poor survival prognosis in head and neck squamous cell carcinoma: Systematic review and meta-analysis.

BACKGROUND: The prognostic roles of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported in head and neck squamous cell carcinoma (HNSCC), but their results remain controversial. METHODS: A total of 25 literatures with 28 cohorts involving 6847 HNSCC patients were included. The hazard ratio (HR) was pooled with 95% confidence interval (CI) using fixed-effects or random-effects models. RESULTS: High pretreatment NLR predicted poor overall survival (OS: HR = 1.68; 95% CI = 1.39-2.03; P < .001), disease-free survival (DFS: HR = 1.76; 95% CI = 1.42-2.17; P < .001), progression-free survival (PFS: HR = 1.53; 95% CI = 1.09-2.14; P = .014), and cancer-specific survival (CSS: HR = 1.45; 95% CI = 1.23-1.71; P < .001) in HNSCC. However, the association between PLR and OS or DFS was not statistically significant. CONCLUSION: The NLR can serve as a potential prognostic biomarker for patients with HNSCC.

AFP-producing hepatoid adenocarcinoma (HAC) of peritoneum and omentum: a case report and literature review.

Hepatoid adenocarcinoma (HAC) is a group of neoplasms with features resembling hepatocellular carcinoma. The stomach is the most commonly affected organ among the reported primary sites. We report the case of a 28-year-old man with chronic hepatitis B and a complaint of abdominal distension. The patient was examined by PET-CT and magnetic resonance imaging (MRI), which showed diffuse thickening of the peritoneum and omentum but no mass was found in the liver. Pathological examination of a biopsy of the omental nodules was consistent with moderately differentiated hepatocellular carcinoma (HCC); thus, a diagnosis of HAC of the peritoneum and omentum was established. The patient received a chemotherapy regimen consisting of oxaliplatin and capecitabine and gained remarkable effects as the AFP level dropped significantly, and the tumour nearly disappeared. When the patient shifted to the standard multikinase inhibitors, Sorafenib or Lenvatinib, both treatments were ineffective. HAC is a heterogeneous group of prognostically unfavourable tumours mimicking the histological appearance of HCC, and the treatment outcomes are still unclear.

[Role of oncologic radiotherapy in multidisciplinary team treatment of malignant acute abdomen].

Malignant acute abdomen is a emergency with abrupt onset, rapid progress and often a complex etiology, presenting difficulties for treatment and high mortality. Therefore, multidisciplinary team (MDT) treatment modality is required. Compared with single-discipline diagnosis and treatment modality, diagnosis made from MDT discussion is more accurate, where specialists can improve efficiency and quality of the treatment through better communication. A good MDT can cover all stages from the diagnosis to the assessment and treatment of the disease, and combine them into a more coherent process. This article discusses the development of radiotherapy-related malignant acute abdomen and the role of radiotherapy in the treatment of malignant acute abdomen from the perspective of oncologic radiotherapy. Common causes of radiotherapy-related acute abdomen from gastric cancer include gastric hemorrhage, upper gastrointestinal obstruction and gastric perforation, while those of radiotherapy-related acute abdomen from colorectal cancer include lower gastrointestinal hemorrhage, intestinal obstruction, intestinal perforation and intestinal fistula. For patients with acute bleeding from gastric cancer that can not be treated by surgery, endoscopic hemostasis or embolization, palliative radiotherapy should be considered. Palliative hypofractionated radiotherapy has the advantage of reducing tumor burden in addition to relieving symptoms of gastric cancer. In patients with acute lower gastrointestinal hemorrhage, as relatively few studies have been established, short course of hypofractionated radiotherapy can be selectively applied. For patients with obstruction, palliative radiotherapy may be considered when surgical assessment is not feasible or tolerable. As malignant acute abdomen has rapid onset and progress, complex etiology and high rate of comorbidity MDT should be fully carried out. For patients with mild symptoms and slow development, radiotherapy can be applied with caution. Emergency treatment such as surgery and intervention should be given when necessary. Passive observation can result in missing the treatment opportunity and should be avoided.

Inhibition of PI3K/AKT Signaling Pathway Radiosensitizes Pancreatic Cancer Cells with ARID1A Deficiency in Vitro.

Pancreatic cancer is among the most aggressive human cancers, and is resistant to regular chemotherapy and radiotherapy. The AT-rich interactive domain containing protein 1A (ARID1A) gene, a crucial chromatin remodeling gene, mutates frequently in a broad spectrum of cancers, including pancreatic cancer. Recent evidence suggests that ARID1A acts as tumor suppressor and plays an important role in DNA damage repair (DDR). However, the effect of ARID1A on the radiosensitivity of pancreatic cancer remains unclear. Herein, we investigated the involvement of ARID1A depletion in the radioresistance of pancreatic cancer cells, and explored the underlying mechanisms. The results reveal that knockdown of ARID1A enhances the radioresistance of pancreatic cancer cells through suppressing apoptosis, impairing G2-M checkpoint arrest, strengthening DDR, and accompanying activation of PI3K/AKT signaling pathway. Moreover, upon inhibition of PI3K/AKT pathway by PI3K-inhibitor LY294002 or AKT-inhibitor mk2206, the radiosensitivity of ARID1A-deficient pancreatic cancer cells is improved in vitro via increased apoptosis and weakened DDR. Taken together, these data suggest that loss of ARID1A expression enhances radioresistance of pancreatic cancer through activation of PI3K/AKT pathway, which maybe a promising target for radiosensitization of ARID1A-deficient pancreatic cancer.

Effects of lentivirus-mediated silencing of Periostin on tumor microenvironment and bone metastasis via the integrin-signaling pathway in lung cancer.

The study aims to investigate the effects of Periostin gene silencing on tumor microenvironment and bone metastasis via the integrin-signaling pathway in lung cancer (LC). LC patients were divided into bone metastasis and non-bone metastasis groups; Healthy volunteers were selected as normal group. ELISA was performed to detect serum Periostin levels and plasma calcium ion concentration. SBC-5 cells were assigned into blank group (without transfection), negative control (NC) group (transfected with empty plasmid), si-Periostin group (transfected with si-Periostin plasmid), si-Integrin-αvß3 group (transfected with Integrin-αvß3 siRNA plasmid) and si-Periostin+si-Integrin-αvß3 group (transfected with si-Periostin and si-Integrin-αvß3 plasmid). qRT-PCR and Western blotting were performed to determine mRNA and protein expression of Periostin, metastasis-associated factors of tumor microenvironment and integrin signaling pathway-related proteins. CCK-8, scratch test and transwell assay were applied to detect cell proliferation, migration and invasion respectively. Nude mouse models of LC bone metastasis were established. TRAP Staining was employed to measure the number of osteoclasts. Bone metastasis group exhibited higher levels of Periostin compared to normal and non-bone metastasis groups. Si-Periostin, si-Integrin-αvß3 and si-Periostin+si-Integrin-αvß3 groups showed decreased Periostin expression, proliferation rate, migration distance, invasive cells, and expressions of metastasis-associated factors of tumor microenvironment and integrin signaling pathway-related proteins compared to blank and NC groups. Similarly, number of osteoclasts and expression of integrin signaling pathway-related proteins were decreased, and bone injury and calcium ion concentration were reduced. The study demonstrated that down-regulation of Periostin expression modulated tumor microenvironment and inhibited bone metastasis by blocking integrin-signaling pathway in LC.

Suppression of CEP55 reduces cell viability and induces apoptosis in human lung cancer.

Centrosomal protein 55 (CEP55), identified as a centrosome­associated protein, has been reported to be involved in human malignancies. However, its biological function in human lung cancer remains largely unknown. In the present study, we firstly analyzed the expression of CEP55 in 20 pairs of lung cancer and matched non­tumor tissues using quantitative RT­PCR analysis and found that CEP55 mRNA was significantly increased in lung cancer tissues compared with that in matched tumor­adjacent tissues. Then we performed a loss­of­function assay using lung cancer cell lines A549 and 95D. Functionally, knockdown of CEP55 markedly inhibited cell viability and proliferation ability as determined by MTT and colony formation assays. Moreover, CEP55­silenced cells were obviously arrested in the G0/G1 phase and presented significant cell apoptosis as determined using flow cytometric analysis. Mechanistically, western blot analysis further revealed that knockdown of CEP55 decreased the expression of CDK4, p21 and Bcl­2, while it increased the expression of pro­apoptotic protein, Bad, caspase­3 and PARP in 95D cells. In conclusion, our data highlight the crucial role of CEP55 in promoting lung cancer cell proliferation in vitro and its inhibition may be a novel therapeutic strategy for lung cancer.