Comparison of S-ketamine and midazolam for intravenous preoperative sedative and anxiolytic effects in preschool children: study protocol for a randomized controlled clinical trial.

BACKGROUND: Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear. METHODS: This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers' and anaesthesia care providers' satisfaction, and mask compliance. DISCUSSION: This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery. TRIAL REGISTRATION: ChiCTR2300069998. Registered on 30 March 2023.

High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer.

BACKGROUND: As a phosphorylated protein, NOLC1 is mainly located in the nucleus and is highly expressed in a variety of tumors, participating in the regulation of cell proliferation and aging. This study further investigated the role of NOLC1 in colorectal cancer tumors, aiming to provide sufficient scientific evidence for the clinical treatment of colorectal cancer. METHODS: We used TCGA, GEO, TNMplot, GEPIA, and other databases to explore the expression level of NOLC1 in colorectal cancer patients, as well as the correlation between the clinical characteristics of colorectal cancer patients and their expression, and conducted the prognostic analysis. Immunohistofluorescence (IHF) staining verified the analytical results. Subsequently, KEGG and GO enrichment analysis was used to identify the potential molecular mechanism of NOLC1 promoting the occurrence and development of colorectal cancer. The influence of NOLC1 expression on the immune microenvironment of colorectal cancer patients was further investigated using the TIMER database. GDSC database analysis was used to screen out possible anti-colorectal cancer drugs against NOLC1. Finally, we demonstrated the effect of NOLC1 on the activity and migration of colorectal cancer cells by Edu Cell proliferation assay and Wound Healing assay in vitro. RESULTS: Our results suggest that NOLC1 is overexpressed in colorectal cancer, and that overexpression of NOLC1 is associated with relevant clinical features. NOLC1, as an independent risk factor affecting the prognosis of colorectal cancer patients, can lead to a poor prognosis of colorectal cancer. In addition, NOLC1 may be associated with MCM10, HELLS, NOC3L, and other genes through participating in Wnt signaling pathways and jointly regulate the occurrence and development of colorectal cancer under the influence of the tumor microenvironment and many other influencing factors. Related to NOLC1: Selumetinib, Imatinib, and targeted drugs such as Lapatinib have potential value in the clinical application of colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. CONCLUSIONS: High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. Further studies and clinical trials are needed to confirm the role of NOLC1 in the development and progression of colorectal cancer.

Antitumor Effect of Demethylzeylasteral (T-96) on Triple-Negative Breast Cancer via LSD1-Mediate Epigenetic Mechanisms.

Background and Purpose. Breast cancer ranks first in the incidence of female tumors. Triple-negative breast cancer (TNBC), one type of breast cancer, is more aggressive and has a worse prognosis. Demethylzeylasteral (T-96) is isolated from Tripterygium wilfordii Hook F. Our previous study found that T96 could inhibit TNBC invasion via suppressing the canonical and noncanonical TGF-ß signaling pathways. However, the antitumor effects and mechanisms of T-96 on TNBC have not been studied. This study is aimed at investigating the antitumor effect and mechanism of T-96 on breast cancer. Experimental approach. MTT assay, Live and Dead cell assay, and TUNEL were used to observe the antitumor effect of breast cancer cells treated with T-96. siRNA of LSD1, Co-IP, and molecular docking were used to explore the direct target and mechanism of T-96. Subcutaneous murine xenograft models were used to detect the efficacy of T-96 antitumor activity in vivo. Key Results. T-96 was more susceptible to inducing the apoptosis of highly metastatic TNBC cell lines (SUM-1315). An abnormal level of histone methylation is a crucial characteristic of metastatic cancer cells. LSD1 is a histone demethylase. We found that T-96 could significantly decrease the protein expression of LSD1, increase its target protein PTEN expression and enhance histone methylation. T-96 could also down-regulate the PI3K/AKT signaling pathway, which could be blocked by PTEN. Knockdown of LSD1 by siRNA blocked the pharmacological activity of T-96. And the molecular docking predicted T-96 processed affinity toward LSD1 through hydrogen bonding. Finally, T-96 was evaluated in a murine xenograft model of SUM-1315 cells. And T-96 could significantly inhibit tumor growth without showing marked toxicity. Conclusions & Implications. The results illustrated that T-96 exerted antitumor activity in highly metastatic TNBC by inactivating the LSD1 function.

Radiotherapy Combined With Concurrent Nedaplatin-Based Chemotherapy for Stage II-III Esophageal Squamous Cell Carcinoma.

Objective: This study was conducted to explore the appropriate radical radiation dose in concurrent chemoradiotherapy (CCRT) for patients with inoperable stage II-III esophageal squamous cell carcinoma (ESCC). Methods: This retrospective study included patients with esophageal cancer (EC) from the database of patients treated at the Affiliated Zhangjiagang Hospital of Soochow University (1/2015-12/2019). Overall survival (OS), progression-free survival (PFS), objective remission rate (ORR), first failure pattern, and toxicities were collected. Results: 112 patients treated with intensity-modulated radiation therapy (IMRT) combined with concurrent chemotherapy of nedaplatin-based regimens were included. Fifty-eight (51.8%) and 54 (48.2%) patients received 60 (HD) and 50.4 (LD) Gy of radiotherapy, respectively. The HD group showed superior OS and a trend for longer PFS compared with the LD group (median OS: 25.5 vs 17.5 months, P = .021; median PFS: 14.0 vs 10.5 months, P = .076). There were more patients with a complete remission (CR) in the HD group than in the LD group (P=.016). The treatment-related toxicities were generally acceptable, but HD radiotherapy would increase the incidence of grade ≥3 late radiotoxicity (22.4% vs 5.6%, P = .011). Conclusion: In nedaplatin-based CCRT for stage II-III ESCC, the radiotherapy dose of 60 Gy achieved a better prognosis. Strengths and limitations of this study: A comparative study of 50.4 Gy and 60 Gy was conducted to evaluate whether 50.4 Gy can be used as a radical radiotherapy dose for inoperable stage II-III esophageal squamous cell carcinoma from a real-world perspective.The highly consistent selection criteria in our study make analysis results highly reliable and scientific.The existing research results support that nedaplatin can be used in concurrent chemoradiotherapy for esophageal squamous cell carcinoma, and this study focuses on the discovery of a better nedaplatin-based combination regimen.The findings of this study are limited to a single-center study with a non-large sample size.Inevitably, recall bias may exist in this retrospective study.Surgery was not involved in the follow-up treatment after concurrent chemoradiotherapy, which may worsen the prognosis of some patients.

Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma.

AT-rich interaction domain 1A (ARID1A) is a tumor suppressor gene that mutates in several cancer types, including breast cancer, ovarian cancer, and colorectal cancer (CRC). In colon adenocarcinoma (COAD), the low expression of ARID1A was reported but the molecular reason is unclear. We noticed that ARID1A low expression was associated with increased levels of miR-185 in the COAD. Therefore, this study aims to explore ncRNA-dependent mechanism that regulates ARID1A expression in COAD regarding miR-185. The expression of ARID1A was tested in COAD cell line under the effect of miR-185 mimics compared with inhibitor. The molecular features associated with loss of ARID1A and its association with tumor prognosis were analyzed using multi-platform data from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) to identify potential signaling pathways associated with ARID1A alterations in colon cancer. Kaplan-Meier survival curve showed that a low level of ARID1A was closely related to low survival rate in patients with COAD. Results showed that inhibiting miR-185 expression in the COAD cell line significantly restored the expression of ARID1A. Further, the increased expression of ARID1A significantly improved the prolonged overall survival of COAD. We noticed that there is a possible relationship between ARID1A high expression and tumor microenvironment infiltrating immune cells. Furthermore, the increase of ARID1A in tumor cells enhanced the response of inflammatory chemokines. In conclusion, this study demonstrates that ARID1A is a direct target of miR-185 in COAD that regulates the immune modulations in the microenvironment of COAD.

MiR-454-3p Promotes Oxaliplatin Resistance by Targeting PTEN in Colorectal Cancer.

Colorectal cancer is one of the most common malignancies worldwide. Oxaliplatin is the first-line chemotherapeutic agent for the treatment of advanced colorectal cancer. However, acquired resistance to oxaliplatin limits its therapeutic efficacy, and the underlying mechanism remains largely unclear. In this study, we compared the expression of a panel of microRNAs (miRNAs) between oxaliplatin-sensitive and -resistant HCT-116 colorectal cancer cells. We found that miR-454-3p was significantly up-regulated in oxaliplatin-resistant cells and was the most differently expressed miRNA. Interestingly, we observed that inhibition of miR-454-3p resensitized resistant cells to oxaliplatin and enhanced oxaliplatin-induced cellular apoptosis. Moreover, we determined that miR-454-3p promoted oxaliplatin resistance through targeting PTEN and activating the AKT signaling pathway. In vivo study revealed that overexpression of miR-454-3p decreased the sensitivity of HCT-116 xenograft tumors to oxaliplatin treatment in a mouse model. Clinically, overexpression of miR-454-3p was associated with decreased responsiveness to oxaliplatin-based chemotherapy, as well as a short progression-free survival. Taken together, our study indicated that the expression of miR-454-3p could be used to predict oxaliplatin sensitivity, and targeting miR-454-3p could overcome oxaliplatin resistance in colorectal cancer.

CarSite-II: an integrated classification algorithm for identifying carbonylated sites based on K-means similarity-based undersampling and synthetic minority oversampling techniques.

BACKGROUND: Carbonylation is a non-enzymatic irreversible protein post-translational modification, and refers to the side chain of amino acid residues being attacked by reactive oxygen species and finally converted into carbonyl products. Studies have shown that protein carbonylation caused by reactive oxygen species is involved in the etiology and pathophysiological processes of aging, neurodegenerative diseases, inflammation, diabetes, amyotrophic lateral sclerosis, Huntington's disease, and tumor. Current experimental approaches used to predict carbonylation sites are expensive, time-consuming, and limited in protein processing abilities. Computational prediction of the carbonylation residue location in protein post-translational modifications enhances the functional characterization of proteins. RESULTS: In this study, an integrated classifier algorithm, CarSite-II, was developed to identify K, P, R, and T carbonylated sites. The resampling method K-means similarity-based undersampling and the synthetic minority oversampling technique (SMOTE-KSU) were incorporated to balance the proportions of K, P, R, and T carbonylated training samples. Next, the integrated classifier system Rotation Forest uses "support vector machine" subclassifications to divide three types of feature spaces into several subsets. CarSite-II gained Matthew's correlation coefficient (MCC) values of 0.2287/0.3125/0.2787/0.2814, False Positive rate values of 0.2628/0.1084/0.1383/0.1313, False Negative rate values of 0.2252/0.0205/0.0976/0.0608 for K/P/R/T carbonylation sites by tenfold cross-validation, respectively. On our independent test dataset, CarSite-II yield MCC values of 0.6358/0.2910/0.4629/0.3685, False Positive rate values of 0.0165/0.0203/0.0188/0.0094, False Negative rate values of 0.1026/0.1875/0.2037/0.3333 for K/P/R/T carbonylation sites. The results show that CarSite-II achieves remarkably better performance than all currently available prediction tools. CONCLUSION: The related results revealed that CarSite-II achieved better performance than the currently available five programs, and revealed the usefulness of the SMOTE-KSU resampling approach and integration algorithm. For the convenience of experimental scientists, the web tool of CarSite-II is available in http://47.100.136.41:8081/.

Incidence and Risk Factors of Postoperative Severe Discomfort After Elective Surgery Under General Anesthesia: A Prospective Observational Study.

PURPOSE: Patient comfort is an important concern in patients receiving surgery, but the seriousness of discomfort during recovery is unknown. We investigated the incidence of postoperative discomfort based on the Standardized Endpoints in Perioperative Medicine initiative for patient comfort, and identified the risk factors. DESIGN: This was a single-center prospective observational study. METHODS: We enrolled adult patients who underwent elective surgery under general anesthesia between July and December 2018 at West China Hospital of Sichuan University (ChiCTR1800017324). The primary outcome was the incidence of postoperative severe discomfort (PoSD), defined as occurring when a patient experienced a severe rating in two or more domains in the six domains in the Standardized Endpoints in Perioperative Medicine initiative on the same day, including rest pain, postoperative nausea, and vomiting, dissatisfaction of gastrointestinal recovery, dissatisfaction of mobilization, sleep disturbance, and recovery. A generalized estimated equation was constructed to find risk factors of PoSD. FINDINGS: In total, 440 patients completed the study. The incidence of PoSD was 28% on postoperative day (POD) 1, 13% on POD 2, 9% on POD 3, and 3.6% on both POD 5 and 7. The most common discomfort was serious sleep disturbance, ranging from 43% to 10% in the first week after surgery. Longer operative time (odds ratio [95% confidence interval]: 1.56 [1.19 to 2.05], P = .001), gastrointestinal surgery (5.03[2.08,12.17], P < .001), orthopaedic surgery (3.03 [1.35,6.79], P = .007), ear, nose, and throat (ENT) surgery (3.50 [1.22,10.02], P = .020) and postoperative complications (1.77 [1.03-3.04], P = .038) were significant risk factors of PoSD. CONCLUSIONS: The incidence of PoSD after elective surgery under general anesthesia is high. Sleep disturbance was the most common problem identified. Anesthesia providers and perianesthesia nurses may need to optimize anesthetic application, combine different anesthesia methods, improve perioperative management, and provide interventions to reduce and to treat discomfort after surgeries.

Immune Checkpoint Blockade in Cancer Immunotherapy: Mechanisms, Clinical Outcomes, and Safety Profiles of PD-1/PD-L1 Inhibitors.

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 are critical for the regulation of T cell exhaustion and activity suppression. Tumor cells expressing immune checkpoints including PD-L1 escape monitoring of T cells from the host immune system. Checkpoint inhibitors are highly promising therapies that function as tumor-suppressing factors via modulation of tumor cell-immune cell interactions as well as boosting T cell-mediated anti-tumor immunity. Notably, PD-1 or PD-L1 monoclonal antibody (mAb) has demonstrated promising therapeutic effects in clinical studies of many types of cancer. These mAbs have caused significant tumor regression with impressive anti-tumor response rates as well as a favorable safety profile in cancer patients. Furthermore, the combination of PD-1/PD-L1 mAbs with other types of anti-tumor agents has also developed to boost the anti-tumor responses and enhance therapeutic effects in cancer patients. This review clarifies the mechanisms of PD-1/PD-L1-mediated anti-cancer immune responses and some clinical studies of mAbs targeting PD-1/PD-L1. The challenges and future of PD-1/PD-L1 blockade therapy are also discussed.

Serum creatinine/cystatin C ratio as a case-finding tool for low handgrip strength in Chinese middle-aged and older adults.

Measuring handgrip strength is the initial step to diagnose sarcopenia. To investigate whether the serum creatinine (Cr)/cystatin C (CysC) ratio could serve as a case-finding tool for low handgrip strength, we conducted a diagnostic accuracy study. Adults (aged ≥ 40 years) with normal renal function were recruited. Trained nurses collected blood samples and conducted the anthropometric measurements and handgrip strength test. The serum concentrations of Cr, CysC, and other biomarkers were measured. We recruited 1098 men and 1241 women. The Cr/CysC ratio was significantly associated with AWGS-defined low handgrip strength among men and women. The areas under the receiver operating characteristic curves were 0.79 among men and 0.78 among women for using the Cr/CysC ratio to identify AWGS-defined low handgrip strength. We set the Cr/CysC ratio cut-off values at < 8.9 among men and < 8.0 among women. The corresponding sensitivity values were 64.9% among men and 63.1% among women, while the specificity values were 83.7% among men and 77.5% among women. In conclusion, the Cr/CysC ratio is positively and linearly associated with handgrip strength and may be helpful for screening low handgrip strength in Chinese middle-aged and older adults dwelling in communities.

Impacts of Preoperative Smoking and Smoking Cessation Time on Preoperative Peripheral Blood Inflammatory Indexes and Postoperative Hospitalization Outcome in Male Patients with Lung Cancer and Surgery Treatment.

Objective s To investigate the effects of preoperative smoking and smoking cessation time on preoperative peripheral blood inflammatory indexes and postoperative hospitalization outcomes in male patients with lung cancer and surgery therapy.Methods We retrospectively enrolled 637 male patients who underwent curative-intent lung cancer resection between January 2014 and December 2016. Patients were classified as the current smokers, the never smokers, and the ex-smokers based on their smoking history, and the ex-smokers were allocated into five subgroups according to their smoking cessation times (CeT): CeT≤6 weeks, 6weeks10years. The preoperative peripheral blood white blood cells (WBCs), albumin, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), intraoperative blood loss, 30-day mortality, in-hospital days, hospitalization costs, intensive care unit (ICU), admission days and placement time of closed thoracic drainage tube were compared among different groups.Results There were significant differences in WBC (F=5.275, P<0.001) and albumin (F=2.470, P<0.05) among patients of current smokers, ex-smokers with different smoking cessation time, and never-smokers. The blood WBC count in current smokers (7.7×10 9/L) was significantly higher than that in ex-smokers (7.0×10 9/L)and never-smokers (5.9×10 9/L) (t=-2.145, P<0.05; t=-6.073, P<0.01, respectively). The level of peripheral blood albumin in current smokers (41.1 g/L) was lower than that in ex-smokers (42.1 g/L) and never-smokers (43.2 g/L) (t=2.323, P<0.05; t=3.995, P<0.01, respectively). The level of peripheral blood NLR in current smokers (3.7) was higher than that in ex-smokers (3.1) and never smokers (2.8) (t=-1.836, P<0.05; t=-2.889, P<0.01, respectively). There was no significant difference in WBC, albumin and NLR among five subgroups of different smoking cessation time. No significant difference was observed in intraoperative blood loss, 30-day mortality, hospitalization costs, hospital stay, ICU stay and placement time of closed thoracic drainage tube among groups either. Conclusion Smoking increases the preoperative inflammatory indexes in peripheral blood of lung cancer patients. Smoking cessation has beneficial effect on reducing levels of these inflammatory indexes, which may be not impacted by the time length of smoking cessation. Therefore, lung cancer patients should be encouraged to quit smoking at any time.

Responses of metastatic primary fallopian tube carcinoma to pembrolizumab and nab-paclitaxel: A case report.

RATIONALE: Primary fallopian tube carcinoma (PFTC) is an extremely rare but invasive malignancy with a dismal prognosis. Very few data exist on the salvage treatment for patients with PFTC. Here we report a case showing an impressive response to immunotherapy combined with chemotherapy, which have never been reported before on patients with metastatic PFTC. PATIENT CONCERNS: A 42-year-old woman, who was diagnosed with PFTC in 2010, had been failed of multiple systemic therapies and antiangiogenic therapy because of the disease recurrence and progression. DIAGNOSIS: Metastatic primary fallopian tube carcinoma. INTERVENTIONS: The patient underwent surgery in May 2010 and had multi-line chemotherapies plus an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody for about 9 years. Due to treatment failure the patient accepted the immunotherapy with the checkpoint inhibitor, pembrolizumab, combined with nab-paclitaxel from December 2018 to April 2019. OUTCOMES: The patient showed a complete response after 6 cycles treatment. Thus far, the patient is taking pembrolizumab as maintenance and remains in good health. LESSONS: Pembrolizumab combined with chemotherapy for treatment of PFTC may provide a positive antitumor effect in multiple metastatic lesions, but more clinical evidence is needed to confirm the efficacy and safety.

2lpiRNApred: a two-layered integrated algorithm for identifying piRNAs and their functions based on LFE-GM feature selection.

Piwi-interacting RNAs (piRNAs) are indispensable in the transposon silencing, including in germ cell formation, germline stem cell maintenance, spermatogenesis, and oogenesis. piRNA pathways are amongst the major genome defence mechanisms, which maintain genome integrity. They also have important functions in tumorigenesis, as indicated by aberrantly expressed piRNAs being recently shown to play roles in the process of cancer development. A number of computational methods for this have recently been proposed, but they still have not yielded satisfactory predictive performance. Moreover, only one computational method that identifies whether piRNAs function in inducting target mRNA deadenylation been reported in the literature. In this study, we developed a two-layered integrated classifier algorithm, 2lpiRNApred. It identifies piRNAs in the first layer and determines whether they function in inducting target mRNA deadenylation in the second layer. A new feature selection algorithm, which was based on Luca fuzzy entropy and Gaussian membership function (LFE-GM), was proposed to reduce the dimensionality of the features. Five feature extraction strategies, namely, Kmer, General parallel correlation pseudo-dinucleotide composition, General series correlation pseudo-dinucleotide composition, Normalized Moreau-Broto autocorrelation, and Geary autocorrelation, and two types of classifier, Sparse Representation Classifier (SRC) and support vector machine with Mahalanobis distance-based radial basis function (SVMMDRBF), were used to construct a two-layered integrated classifier algorithm, 2lpiRNApred. The results indicate that 2lpiRNApred performs significantly better than six other existing prediction tools.

The Critical Role of Cannabinoid Receptor 2 in URB602-Induced Protective Effects Against Renal Ischemia-Reperfusion Injury in the Rat.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage. Accumulating proofs demonstrates that the endocannabinoid system may provide a promising access for treatment strategy of renal IRI associated AKI. In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation. Using Western blot analysis and LC-MS/MS, renal IRI showed to increase the levels of 2-arachidonoylglycerol (2-AG) in kidneys as well as COX-2, PGE2, TXA2, and decrease N-arachidonoylethanolamine (anandamide, AEA); the expressions of renal cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) were unchanged. The URB602 pretreatment in renal IRI, further enhanced renal 2-AG which is high affinity to both CB1 and CB2, and reduced renal COX-2 which is involved in the regulation of renal perfusion and inflammation. AM630 (CB2 antagonist) almost blocked all the antioxidant, anti-inflammatory and nephroprotective effects of URB602, whereas AM251 (CB1 antagonist) showed limited influence, and parecoxib (COX-2 inhibitor) slightly ameliorated renal function at the dose of 10 mg/kg. Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.

What Is the Optimal Radiotherapy Target Size for Non-Operable Esophageal Cancer? A Meta-Analysis.

Definitive radiotherapy has an affirmative role in treating non-operable esophageal cancer; however, the controversy between elective lymph node irradiation (ENI) and involved-field irradiation (IFI) still remains. To ascertain the benefits and disadvantages of the two radiation target volumes, we performed a meta-analysis with 7 related publications. According to our findings, patients treated with ENI and IFI had nearly identical 1, 2, and 3-year survival rates (pooled odds ratio [OR] = 1.004, p = 0.980, and pooled OR = 1.15, p = 0.594, and pooled OR = 0.918, p = 0.679, respectively). Likewise, no significant differences were detected in local recurrence rates (pooled OR = 1.04, p = 0.883), regional recurrence rates (pooled OR = 0.65, p = 0.555), and distant metastasis rates (pooled OR = 1.29, p = 0.309) between the two treatment groups. However, IFI could significantly decrease the incidences of acute radiation esophagitis (pooled OR = 2.30, p = 0.001) and late pneumonia (pooled OR = 2.52, p = 0.04) compared with ENI. This meta-analysis provides evidence that IFI is more feasible for non-operable esophageal cancer than ENI.

Nedaplatin-based chemotherapy regimens combined with concurrent radiotherapy as first-line treatment for stage II-III esophageal squamous cell carcinoma.

Concurrent chemoradiotherapy (CCRT) is an effective first-line treatment for esophageal squamous cell carcinoma (ESCC). The present study aimed to compare clinical outcomes between three nedaplatin-based regimens for CCRT of ESCC. Patients with stage II-III thoracic ESCC in China between January 2012 and May 2016 were included. Patients received esophageal ultrasonography prior to treatment. Chemotherapy was as follows: i) 100 mg/m2 nedaplatin intravenously on day 1 and 70 mg/m2 tegafur-gimeracil-oteracil potassium (S-1) orally twice daily for 2 weeks; ii) 50 mg/m2 nedaplatin intravenously on days 1 and 2 and 35 mg/m2 docetaxel intravenously on days 1 and 8; or iii) 60 mg/m2 nedaplatin intravenously on days 1 and 2. Intensity-modulated radiotherapy was used to administer a total dose of 60-66 Gy (1.8-2.0 Gy per fraction) to the primary tumor and 45-50 Gy to the subclinical region. A total of 70 patients were enrolled (median age, 66 years; range, 50-81 years). T4 disease was identified in 45 (64.3%) patients. All patients completed radiotherapy and received ≥2 chemotherapy cycles. Estimated 1-, 2- and 3-year overall survival (OS) rates were 82.9, 53.9 and 31.4%, respectively. OS and progression-free survival were similar between the three treatment groups. Grade 3/4 hematological toxicities were observed in 35 (50%) patients. The incidence of serious treatment-associated toxicities was numerically highest for the nedaplatin/docetaxel combination. Patients with thoracic ESCC had good clinical outcomes following CCRT. With similar survival rates and disease responses yet lower hematological toxicities, nedaplatin/S-1 and single-agent nedaplatin may be preferable to nedaplatin/docetaxel. Poor control of distant metastasis may be a disadvantage of single-agent chemotherapy use in CCRT, and a further study with larger cohorts is required to confirm this.

Comparing Mini Sarcopenia Risk Assessment With SARC-F for Screening Sarcopenia in Community-Dwelling Older Adults.

OBJECTIVE: The Mini Sarcopenia Risk Assessment (MSRA), a new sarcopenia screening tool, has 2 versions: MSRA-7 (full version, 7 items) and MSRA-5 (short version, 5 items). We aimed to compare the diagnostic values of MSRA-7 and MSRA-5 to SARC-F for screening sarcopenia. DESIGN: A diagnostic accuracy study. SETTING: A community in Chengdu, China. PARTICIPANTS: Older adults. MEASUREMENTS: Muscle mass, strength, and physical performance were tested using a bioimpedance analysis (BIA) device, handgrip strength, and walking speed, respectively. Using the Asian Working Group for Sarcopenia (AWGS) criteria as the gold standard, the sensitivity/specificity analyses of the 3 scales were assessed. Receiver operating characteristic (ROC) curves and area under the ROC curves (AUC) were used to compare the overall diagnostic accuracy of the 3 scales. RESULTS: We recruited 384 participants. Against the AWGS criteria, SARC-F had a sensitivity of 29.5% and a specificity of 98.1%, and the MSRA-7 had a sensitivity of 86.9% and a specificity of 39.6%, whereas the MSRA-5 had a sensitivity of 90.2% and a specificity of 70.6%. The AUCs of SARC-F, MSRA-7, and MSRA-5 were 0.89 [95% confidence interval (CI), 0.86-0.92], 0.70 (95% CI, 0.65-0.74), and 0.85 (95% CI, 0.81-0.89), respectively. The differences in AUCs between SARC-F and MSRA-7 and in those between MSRA-7 and MSRA-5 were statistically significant (P <.001), but the difference between SARC-F and MSRA-5 was not statistically significant (P = .130). CONCLUSION: MSRA-5 may serve as a novel screening tool for sarcopenia in Chinese community-dwelling older adults. SARC-F, a class screening tool, is also suitable for this population. MSRA-5 and SARC-F demonstrated a similar diagnostic accuracy in our study population. MSRA-5 has better sensitivity, whereas SARC-F has better specificity. However, the diagnostic value of MSRA needs to be further validated in different populations.

Triptonide inhibits human nasopharyngeal carcinoma cell growth via disrupting Lnc-RNA THOR-IGF2BP1 signaling.

Advanced stage nasopharyngeal carcinoma (NPC) has a poor prognosis. Triptonide ("TN") is a small molecule monomer extract from the ancient Chinese herb Tripterygium wilfordii Hook. We show that TN, at nanomolar concentrations, potently inhibited survival and proliferation of multiple established and primary human NPC cells. TN induced NPC cell cycle arrest and apoptosis activation. NPC cell migration and invasion were also inhibited by TN. Importantly, TN was non-cytotoxic to nasopharyngeal epithelial cells. TN treatment in NPC cells disrupted LncRNA THOR ("Lnc-THOR")-IGF2BP1 association, causing depletion of Lnc-THOR and downregulation of IGF2BP1 mRNA targets (Myc, IGF2 and Gli1). Lnc-THOR or IGF2BP1 knockout by CRISPR/Cas9 gene-editing methods mimicked and abolished TN's actions in NPC cells. Conversely, ectopic Lnc-THOR overexpression inhibited TN-induced cytotoxicity in NPC cells. Significantly, Lnc-THOR, IGF2BP1 and its mRNA targets are elevated in human NPC tissues and cells, but almost undetectable in nasopharyngeal epithelial tissues and cells. In vivo, intraperitoneal TN administration significantly inhibited subcutaneous NPC xenograft growth in mice. Similarly, Lnc-THOR-knockout HONE-1 xenografts grew significantly slower than control tumors. Thus, TN inhibits human NPC cell growth in vitro and in vivo via disrupting Lnc-THOR-IGF2BP1 signaling.

SARC-F for sarcopenia screening in community-dwelling older adults: Are 3 items enough?

A 3-item SARC-F (termed SARC-F-3 in our study) was recently suggested as a screening tool for sarcopenia.The aim of this study was to compare the diagnostic value of SARC-F-3 to SARC-F in community-dwelling older people.We conducted a diagnostic accuracy study in an urban community in Chengdu, China. People aged 60 years or older were included. Muscle mass, strength, and physical performance were measured by a bio-impedance analysis (BIA) device, handgrip strength, and gait speed test, respectively. The Asia Working Group for Sarcopenia (AWGS) criteria were applied as the "gold reference." The sensitivity/specificity analyses of SARC-F and SARC-F-3 were performed. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were applied to compare the overall accuracy of SARC-F and SARC-F-3. The cut-off points of SARC-F-3 for sarcopenia were determined using the Youden index method.A total of 384 older people aged 71.5 ±â€Š5.8 years were included. On the basis of the AWGS criteria, the prevalence of sarcopenia in our study population was 15.9%. The optimal cut-off point of SARC-F-3 for identifying sarcopenia was a total score of ≥ 2. In the whole study population, the sensitivity and specificity of SARC-F were 29.5% [95% confidence interval (95% CI): 18.5-42.6] and 98.1% (95% CI: 96.0-99.3), respectively, whereas the sensitivity and specificity of SARC-F-3 were 13.1% (95% CI: 5.8-24.2) and 97.8% (95% CI: 95.6-99.1), respectively. The AUCs of SARC-F and SARC-F-3 were 0.894 (95% CI: 0.859-0.923) and 0.676 (95% CI: 0.627-0.723), respectively (P < .001).The 3-item SARC-F may not be suitable for screening sarcopenia in community-dwelling older people.

Inhibition of HHIP Promoter Methylation Suppresses Human Gastric Cancer Cell Proliferation and Migration.

BACKGROUND/AIMS: Human hedgehog-interacting protein (HHIP) is a negative regulator of the hedgehog (HH) signaling pathway. It is deregulated in gastric cancer. The underlying molecular mechanism of HHIP-induced inhibition of HH signaling remains to be determined. METHODS: A lentiviral HHIP expression vector ("LV-HHIP") was established to exogenously over-express HHIP in gastric cancer cells. HHIP protein and mRNA were tested by Western blotting assay and quantitative real-time PCR assay, respectively. Cell survival was tested by the Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was examined by the BrdU ELISA assay and [H3] Thymidine DNA incorporation assay. Cell invasion and migration were tested by the phagokinetic track assay and the "Transwell" assay. The bisulfite-sequencing PCR was applied to test HHIP promoter methylation. RESULTS: In the established (AGS cell line) and primary human gastric cancer cells, LV-HHIP transfection increased HHIP expression and inhibited cancer cell survival and proliferation as well as cell migration and invasion. Furthermore, LV-HHIP significantly attenuated promoter methylation of the endogenous HHIP gene in AGS cells, causing it upregulation. Inhibition of methylation by 5-aza-dc similarly induced HHIP expression in gastric cancer cells, which inhibited cancer cell proliferation and migration. CONCLUSIONS: Our results suggest that inhibition of HHIP promoter methylation can efficiently inhibit human gastric cancer cell proliferation and migration.