Next-generation spatial transcriptomics: unleashing the power to gear up translational oncology.

The growing advances in spatial transcriptomics (ST) stand as the new frontier bringing unprecedented influences in the realm of translational oncology. This has triggered systemic experimental design, analytical scope, and depth alongside with thorough bioinformatics approaches being constantly developed in the last few years. However, harnessing the power of spatial biology and streamlining an array of ST tools to achieve designated research goals are fundamental and require real-world experiences. We present a systemic review by updating the technical scope of ST across different principal basis in a timeline manner hinting on the generally adopted ST techniques used within the community. We also review the current progress of bioinformatic tools and propose in a pipelined workflow with a toolbox available for ST data exploration. With particular interests in tumor microenvironment where ST is being broadly utilized, we summarize the up-to-date progress made via ST-based technologies by narrating studies categorized into either mechanistic elucidation or biomarker profiling (translational oncology) across multiple cancer types and their ways of deploying the research through ST. This updated review offers as a guidance with forward-looking viewpoints endorsed by many high-resolution ST tools being utilized to disentangle biological questions that may lead to clinical significance in the future.

Treatment strategies and molecular mechanism of radiotherapy combined with immunotherapy in colorectal cancer.

Radiotherapy (RT) remodels the tumor immune microenvironment (TIME) and modulates the immune response to indirectly destroy tumor cells, in addition to directly killing tumor cells. RT combined with immunotherapy may significantly enhance the efficacy of RT in colorectal cancer by modulating the microenvironment. However, the molecular mechanisms by which RT acts as an immunomodulator to modulate the immune microenvironment remain unclear. Further, the optimal modalities of RT combined with immunotherapy for the treatment of colorectal cancer, such as the time point of combining RT and immunization, the fractionation pattern and dosage of radiotherapy, and other methods to improve the efficacy, are also being explored parallelly. To address these aspects, in this review, we summarized the mechanisms by which RT modulates TIME and concluded the progress of RT combined with immunization in preclinical and clinical trials. Finally, we discussed heavy ion radiation therapy and the efficacy of prediction markers and other immune combination therapies. Overall, combining RT with immunotherapy to enhance antitumor effects will have a significant clinical implication and will help to facilitate individualized treatment modalities.

Naringenin roled octacalcium phosphate reinforced with polyvinyl alcohol composite for sarcoma affected bone repair.

Osteosarcoma is a rare cancer affecting disease for children and young adults; complete healing from this condition is quite difficult. Recently, new regeneration materials have been preferred, including natural compound companied implants for affected bone repair, and it is effectively used to treat osteosarcoma disease. Hence, Octa calcium phosphate (OCP) reinforced with poly (vinyl alcohol) (PVA) and oleic acid (OA) with Naringenin (NRG) composite was prepared and studied to cure the sarcoma affected bone. The physicochemical nature of the prepared OCP, PVA/OA/OCP, and PVA/OA/OCP/NRG composite were characterized by FT-IR, SEM, and XRD techniques. The in vitro release of the NRG from the PVA/OA/OCP/NRG composite was evaluated by UV-visible spectroscopy and the NRG release rate was observed at 98.0 % over 24 h. Biocompatibility and cell viability of the prepared OCP, PVA/OA/OCP, and PVA/OA/OCP/NRG composite are investigated in adipose-derived stem cells (ASCs) on different days. Interestingly, the PVA/OCP/OA/NRG composite shows an increase of 74.0 % to 92.0 % in cell survival, indicating that the composite is biocompatible. Similarly, the ability of NRG in the composite is to suppress cancer cells and it was determined in lung cancer (A549) cells. NRG-loaded PVA/OCP/OA/NRG shows good inhibition ability, nearly 43 % at 72 h. From the results, the prepared composite materials can inhibit cancer cells and be viable in stem cell growth. Since the materials will serve as potential regenerative materials for sarcoma-affected bone recovery.

Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial.

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics.

Background: The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyroptosis is a worthwhile topic for improving the precision treatment and prognosis prediction of CRC. Methods: We classified patients into two clusters using the consensus clustering based on the pyroptosis-related genes (PRGs). Next, the prognostic signature was developed with LASSO regression analysis using the screened genes from differentially expressed genes (DEGs) by univariate and multivariate Cox analyses. According to the pyroptosis-related score (PR score) calculated with the signature, patients belonged to two groups with distinct prognosis. Moreover, we assessed the immune profile to explore the relationship between the signature and immunological characteristics. Two single cell sequencing databases were adopted for further exploration of tumor immune microenvironment (TME). In addition, we applied our own cohort and Drugbank to explore the correlation of the signature and clinical therapies. We also studied the expression of key genes by immunohistochemistry. Results: The signature performed well in predicting the prognosis of CRC as the high area under curve (AUC) value demonstrated. Patients with a higher PR score had poorer prognosis and higher expression of immune checkpoints but more abundant infiltration of immune cells. Combining with the indicator of therapeutic analysis, they might benefit more from immune checkpoint blockade (ICB) and neo-adjuvant chemoradiotherapy (nCRT). Conclusion: In conclusion, our study is based on genomics and transcriptomics to investigate the role of PRGs in CRC. We have established a prognostic signature and integrated single-cell data to study the relationship between the signature with the TME in CRC. Its clinical application in reliable prediction of prognosis and personalized treatment was validated by public and own sequencing cohort. It provided a new insight for the personalized treatment of CRC.

Unraveling Colorectal Cancer and Pan-cancer Immune Heterogeneity and Synthetic Therapy Response Using Cuproptosis and Hypoxia Regulators by Multi-omic Analysis and Experimental Validation.

Cuproptosis, a new type of programmed cell death (PCD), is closely related to cellular tricarboxylic acid cycle and cellular respiration, while hypoxia can modulate PCD. However, their combined contribution to tumor subtyping remains unexplored. Here, we applied a multi-omics approach to classify TCGA_COADREAD based on cuproptosis and hypoxia. The classification was validated in three colorectal cancer (CRC) cohorts and extended to a pan-cancer analysis. The results demonstrated that pan-cancers, including CRC, could be divided into three distinct subgroups (cuproptosis-hypoxia subtypes, CHSs): CHS1 had active metabolism and poor immune infiltration but low fibrosis; CHS3 had contrasting characteristics with CHS1; CHS2 was intermediate. CHS1 may respond well to cuproptosis inducers, and CHS3 may benefit from a combination of immunotherapy and anti-fibrosis/anti-hypoxia therapies. In CRC, the CHSs also showed a significant difference in prognosis and sensitivity to classic drugs. Organoid-based drug sensitivity assays validated the results of transcriptomics. Cell-based assays indicated that masitinib and simvastatin had specific effects on CHS1 and CHS3, respectively. A user-friendly website based on the classifier was developed (https://fan-app.shinyapps.io/chs_classifier/) for accessibility. Overall, the classifier based on cuproptosis and hypoxia was applicable to most pan-cancers and could aid in personalized cancer therapy.

A cross-sectional study on the mental health of patients with COVID-19 1 year after discharge in Huanggang, China.

OBJECTIVE: This study is aimed to investigate the mental health status of COVID-19 survivors 1 year after discharge from hospital and reveal the related risk factors. METHODS: From April 11 to May 11, 2021, 566 COVID-19 survivors in Huanggang city were recruited through their primary doctors. A total of 535 participants (94.5%) admitted to participate in the survey and completed the questionnaires. Five scales were applied including 7-Items Generalized Anxiety Disorder Scale, Patient Health Questionnaire-9, Impact of Event Scale-Revised, Pittsburgh Sleep Quality Index, and Fatigue Scale-14. The chi-square and the Fisher's exact test were used to evaluate the classification data, multivariate logistic regression was used to explore the related factors of sleep quality, fatigue, anxiety, depression, and post-traumatic stress disorder (PTSD). RESULTS: One year after being discharged, of the 535 COVID-19 survivors, 252 (47.1%) had poor sleep quality; 157 (29.3%) had the symptoms of fatigue; 84 (15.7%),112 (20.9%), and 130 (24.3%) suffered from symptoms of anxiety, depression, and PTSD, respectively. The logistic regression analysis showed that history of chronic disease was risk factor for poor sleep quality (OR 2.501; 95% CI, 1.618-3.866), fatigue (OR 3.284; 95% CI 2.143-5.033), PTSD (OR 2.323; 95% CI 1.431-3.773) and depression (OR 1.950; 95% CI 1.106-3.436) in COVID-19 survivors. Smoking contributed to the poor sleep quality (OR 2.005; 95% CI 1.044-3.850), anxiety (OR 4.491; 95% CI 2.276-8.861) and depression (OR 5.459; 95% CI 2.651-11.239) in survivors. Drinking influenced fatigue (OR 2.783; 95% CI 1.331-5.819) and PTSD (OR 4.419; 95% CI 1.990-9.814) in survivors. Compared with college-educated survivors, survivors with high school education were at higher risk for poor sleep quality (OR 1.828; 95% CI 1.050-3.181) and PTSD (OR 2.521; 95% CI 1.316-4.830), and survivors with junior high school education were at higher risk for PTSD (OR 2.078; 95% CI 1.039-4.155). Compared with overweight survivors (BMI ≥ 23.0), survivors with normal BMI (18.5-22.9) (OR 0.600; 95% CI 0.405-0.889) were at lower risk for fatigue. While being housewife (OR 0.390; 95% CI 0.189-0.803) was protective factor for fatigue and having more family members was protective factor for PTSD (OR 0.404 95% CI 0.250-0.653) in survivors. CONCLUSIONS: One year after infection, poor sleep quality, fatigue, anxiety, depression, and PTSD, still existed in a relatively high proportion of COVID-19 survivors. Chronic disease history was an independent risk factor for poor sleep quality, fatigue, depression, and PTSD. Participants with low education levels were more likely to have mental problems than the others. We should focus on the long-term psychological impact of COVID-19 on survivors, and the government should apply appropriate mental health services to offer psychiatric support.

The Global States and Hotspots of ERAS Research From 2000 to 2020: A Bibliometric and Visualized Study.

Background: Enhanced recovery after surgery (ERAS) protocol has been implemented in surgeries for more than 20 years, this study investigated the global states and hotspots of ERAS research. Methods: Based on the Web of Science database, a bibliometric and visualized study of original ERAS research from 2000 to 2020 was performed, including the trends of publications and citations; distribution of countries, authors, institutions, sources; study design, level of evidence, served surgeries and surgical disciplines. Hotspots were revealed by research interests and keywords. Results: Within the field of original ERAS research, there was a rising trend in annual publications and citations. The USA was the greatest contributor. Kehlet, H, University of Copenhagen were the most influential author and institution, respectively. British Journal of Surgery and Annals of Surgery were the most cited journals. Though there were more prospective designs, more than half of the studies presented level IV evidence and had fewer citations and citation densities compared to that of level II and level III. ERAS protocol was overwhelmingly implemented in colorectal surgeries. Most studies focused on elements of ERAS, the top three research interests were "length of stay," "pain management," and "complications." In recent years, bariatric surgery, compliance with ERAS, and feasibility in the elderly were new hotspots. Conclusion: Revealing the global states and hotspots can help researchers better understand the trends in ERAS research. The USA was the greatest contributor to ERAS research. Kehlet, H, was the most influential author in the field. Bariatric surgery, compliance with ERAS, and feasibility in the elderly represent the new trend of ERAS research. Most of the ERAS research had a low evidence levels, studies with high-level evidence are still required in this field.

Linc00963 Promote Cell Proliferation and Tumor Growth in Castration-Resistant Prostate Cancer by Modulating miR-655/TRIM24 Axis.

Previous studies have shown that both long intergenic non-coding RNA 00963 (Linc00963) and tripartite motif containing 24 (TRIM24) are activators of the PI3K/AKT pathway, and both are involved in the carcinogenesis and progression of prostate cancer. However, the regulatory mechanisms between Linc00963 and TRIM24 are still unclear. In this study, we aimed to elucidate the underlying relationship between Linc00963 and TRIM24 in castration-resistant prostate cancer (CRPC). We found that TRIM24, an established oncogene in CRPC, was positively correlated with Linc00963 in prostate cancer tissues. In addition, TRIM24 was positively regulated by Lin00963 in CRPC cells. Mechanistically, TRIM24 was the direct target of microRNA-655 (miR-655) in CRPC cells, and Linc00963 could competitively bind miR-655 and upregulate TRIM24 expression. Using gain- and loss-of- function assays and rescue assays, we identified that miR-655 inhibits TRIM24 expression and cell proliferation and colony forming ability in CRPC, and that Linc00963 promotes TRIM24 expression, cell proliferation, and colony forming ability of CRPC cells by directly suppressing miR-655 expression. We further identified that Linc00963 could promote tumor growth of CRPC cells by inhibiting miR-655 and upregulating TRIM24 axis in vivo. Taken together, our study reveals a new mechanism for the Linc00963/miR-655/TRIM24 competing endogenous RNA (ceRNA) network in accelerating cell proliferation in CRPC in vitro and in vivo, and suggests that Linc00963 could be considered a novel therapeutic target for CRPC.

Targeting SNHG3/miR-186-5p reverses the increased m6A level caused by platinum treatment through regulating METTL3 in esophageal cancer.

BACKGROUND: Platinum-based chemotherapy is a mainstay for treating esophageal cancer patients. In this manuscript, we have provided clues for influence of platinum on overall m6A level and further investigated the potential regulatory mechanism. METHODS: qRT-PCR was used to measure SNHG3 and miR-186-5p expression; ELISA and western blot were used to measure the expression of METTL3. CCK8 was used to measure the cell proliferation rate. Caspase 3/7 activity was used to measure the apoptosis rate. Dual luciferase reporter gene assay and RNA pull down assay were used to investigate the potential crosstalk between miR-186-5p and SNHG3; and miR-186-5p and METTL3. RESULTS: m6A level was increased when treated with platinum (CDDP, CPB and L-OHP). Besides, SNHG3 expression was induced and miR-186-5p expression was suppressed by platinum. Furthermore, SNHG3 could promote the m6A level, however miR-186-5p inhibited the m6A level through targeting METTL3. SNHG3 interacts with miR-186-5p to negatively regulate the expression of miR-186-5p; and miR-186-5p might bind to the 3'UTR of METTL3 to regulate its expression. CONCLUSION: Platinum can increase the overall m6A level of esophageal cancer. SNHG3/miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. Our manuscript has provided clues that regulating m6A level might be a novel way to enhance the platinum efficacy.

CircACC1 Promotes NSCLC Proliferation via miR-29c-3p/MCL-1 Signaling Pathway.

Non-small cell lung cancer remains the leading cause of cancer-related deaths worldwide with high morbidity and mortality. There is an urgent need to reveal new molecular mechanisms that contribute to NSCLC progression to facilitate drug development and to improve overall survival. Much attention has been paid to the role of circRNAs in NSCLC development. However, the knowledge of circRNAs in NSCLC is still limited, and need to be further explored. The dysregulation of circACC1 was evaluated by qRT-PCR in NSCLC samples and cell lines. The oncogenic role of circACC1 in NSCLC progression was analyzed by CCK8 and colony formation assays. The interaction between the circACC1 and miR-29c-3p, as well as MCL-1, was verified by qRT-PCR, Western blot, luciferase reporter assay, and RIP experiment. Elevated levels of circACC1 were found in NSCLC patients and were negatively correlated with OS. Ectopic expression of circACC1 promoted the capacity of cell growth and clonogenicity, while the inhibition of circACC1 decreased the proliferation and clonogenicity potential. Mechanism studies elucidated that circACC1 contributes to cell growth via directly binding to miR-29c-3p. Transfection of miR-29c-3p mimic blocked circACC1 mediated NSCLC cell proliferation. MCL-1 is a downstream target of miR-29c-3p in NSCLC cells. The circACC1/miR-29c-3p/MCL-1 axis is important in NSCLS proliferation.

Long Non-coding RNA SNHG17 Promotes Cell Proliferation and Invasion in Castration-Resistant Prostate Cancer by Targeting the miR-144/CD51 Axis.

Previously, we found that the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) was up-regulated in castration-resistant prostate cancer (CRPC) cells compared to that in hormone sensitive prostate cancer (HSPC) cells. Moreover, we found that CD51 was up-regulated in prostate cancer cells and promoted the carcinogenesis and progression of prostate cancer. However, the regulatory mechanism of SNHG17 and CD51 in the development of CRPC remains unclear. In the current study, we aimed to elucidate the expressions, functions, and underlying mechanism of SNHG17 and CD51 in CRPC. Our results further confirmed that both SNHG17 and CD51 were up-regulated in CRPC tissues and cells. In addition, we found that SNHG17 expression was positively correlated with CD51 expression in prostate cancer. Mechanically, SNHG17 functioned as a competing endogenous RNA (ceRNA) to up-regulate CD51 expression through competitively sponging microRNA-144 (miR-144), and CD51 was identified as a direct downstream target of miR-144 in CRPC. Functionally, down-regulation of SNHG17 or up-regulation of miR-144 inhibited the proliferation, migration, and invasion of CRPC cells, whereas up-regulation of SNHG17 and down-regulation of miR-144 promoted the proliferation, migration and invasion of CRPC cells in vitro and in vivo. Using gain and loss-of function assay and rescue assay, we showed that miR-144 inhibited cell proliferation, migration and invasion by directly inhibiting CD51 expression, and SNHG17 promoted cell proliferation, migration and invasion by directly enhancing CD51 expression in CRPC cells. Taken together, our study reveals the role of the SNHG17/miR-144/CD51 axis in accelerating CRPC cell proliferation and invasion, and suggests that SNHG17 may serve as a novel therapeutic target for CRPC.

Effect of miR-196a inhibition on esophageal cancer growth in vitro.

Esophageal cancer has recent shown a higher incidence but lower 5-year survival rate after normal clinical treatment in China. The aim of this study was to observe whether the inhibition of miR-196a affects esophageal cancer cell growth by modulating the nuclear factor-κB target gene and to detect the possible cooperative therapeutic effects on esophageal cancer by knocking down miR-196a expression combined with the specific inhibitor of nuclear factor-κB target genes. Thus, anti-miR-196a or sotrastaurin, a protein kinase C (PKC) inhibitor, were used to alter PKC expression. We found that miR-196a knockdown or PKC inhibition by sotrastaurin changed PKC expression which then reduced esophageal cancer cell proliferation and downregulated proliferating cell nuclear antigen expression via the classical B-cell receptor-PKC nuclear factor-κB pathway but not the alternative pathway; in addition, miR-196a inhibition can increase the caspase level and induce esophageal cancer cell apoptosis. Our current results provided the evidence that miR-196a was related to the classical nuclear factor-κB pathway, and these new findings proved the potential therapeutic effect of miR-196a in targeted therapy for clinical esophageal cancer patients.

Evaluation of antiarthritic activity of ginkgolic acid against Freund's adjuvant induced arthritic rat model

This study aimed to analyze the antiarthritic activity of ginkgolic acid against the Complete Freund's Adjuvant (CFA)-induced arthritis in rats. Arthritis was induced through an intradermal injection of CFA (0.1 mL) at the right hind footpad of adult Wistar Albino rats. Ginkgolic acid was administered orally at doses of 25 mg/kg and 50 mg/kg, respectively, once daily via gavage for 25 days upon inducing arthritis. Indomethacin was administered orally at a dose of 3 mg/kg twice in a week which served as positive control group. The animals were sacrificed and subjected to biochemical and histopathological analysis upon completion of treatment. Ginkgolic acid was able to reverse the arthritic effect (p < 0.01) induced by CFA in a dose dependent manner. Swelling of paw, thymus and spleen index, serum biomarker levels, and pro-inflammatory cytokines were significantly reduced (p < 0.01) by the acid whereas the antioxidant enzyme activities were remarkably restored. The histopathological findings were in agreement with the biochemical results. The results indicate that the antioxidant and anti-inflammatory properties of ginkgolic acid can be credited to the antiarthritic effects, and it can be promoted as a potential agent for therapeutic use against osteoarthritis

Saikosaponin-d Increases the Radiosensitivity of Hepatoma Cells by Adjusting Cell Autophagy.

Radiotherapy for liver cancer can affect the level of autophagy in cells, and effective autophagy regulation can increase the radiosensitivity of liver cancer cells.Saikosaponin-d (SSd) is an effective active ingredient extracted from traditional Chinese medicine Bupleurum. We have confirmed previously in vitro and in vitro experiments that SSd can significantly induce apoptosis of liver cancer cells, increase the radiosensitivity of liver cancer cells.This study explored the role of autophagy in SSd-mediated radiosensitivity of liver cancer cells. MTT and clone formation experiments showed that radiation can inhibit the proliferation of hepatoma cells and reduce the colony formation of hepatoma cells. After the addition of SSd, the inhibitory effect of radiation on the proliferation and clonal formation of hepatoma cells was further enhanced. However, the addition of the autophagy inhibitor chloroquine or mTOR agonist can partially reverse the inhibitory effect of the combined treatment of SSd with radiation on the proliferation of hepatoma cells. Similarly, transmission electron microscopy and laser confocal microscopy showed that after the addition of SSd, the number of radiation-induced autophagosomes increased significantly in hepatoma cells and the intervention of mTOR agonist can reduce the formation of autophagosomes in hepatoma cells.In addition,Western blot analysis presented that radiation significantly increased LC3-II levels. Especially when SSd is added, LC3-II levels is further increased. Our data indicate that SSd can inhibit the growth of liver cancer cells and enhance cell radiosensitivity by inducing autophagy formation.

Cinobufotalin as an effective adjuvant therapy for advanced gastric cancer: a meta-analysis of randomized controlled trials.

Purpose: This study aimed to investigate the efficacy and safety of combining cinobufotalin and chemotherapy for advanced gastric cancer (GC). Patients and methods: Literature retrieval was performed in Cochrane Library, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biological Medicine Database (CBM), Wanfang database and Chinese Scientific Journal Database (VIP) before September 2018. The primary reported outcomes including therapeutic efficacy, quality of life (QoL), and adverse events were systematically evaluated. Results: Data from 27 trials including 1,939 advanced GC patients were included. The results indicated that, compared with chemotherapy alone, the combination of chemotherapy and cinobufotalin significantly improved patients' overall response rate (odds ratio [OR] =1.88, 95% confidence interval [CI] =1.54-2.31, P<0.00001) and disease control rate (OR =2.05, 95% CI =1.63-2.58, P<0.00001). The QoL of patients also evidently improved after chemotherapy and cinobufotalin combined treatment, as indicated by increased QoL improved rate (OR =2.39, 95% CI =1.81-3.15, P<0.00001), Karnofsky Performance Score (OR =7.00, 95% CI =2.25-11.75, P=0.004) and pain relief rate (OR =7.00, 95% CI =2.25-11.75, P=0.004). Adverse events including nausea and vomiting, diarrhea, leukopenia, hand-foot syndrome, anemia, gastrointestinal side effects and peripheral neurotoxicity caused by chemotherapy were evidently alleviated (P<0.05) when cinobufotalin was administered to GC patients. Conclusion: Evidence from the meta-analysis suggested that the combination of chemotherapy and cinobufotalin is more effective in treating GC than chemotherapy alone. It alleviates the adverse effects associated with chemotherapy and improves the QoL of GC patients.

Inhibition of miR-196a affects esophageal cancer cell growth in vitro.

Esophageal cancer (EC) is one of the most common causes of cancer-related mortality worldwide. Several oncogenes such as miR-196a have been implicated in the carcinogenesis and progression of EC. The purpose of this study was to determine the effects of anti-miR-196a on the growth and survival of human EC cells in vitro. We found that miR-196a was highly expressed in both TE1 and EC109 cells and that miR-196a knockdown inhibited cell proliferation and migration. Furthermore, miR-196a knockdown sensitized EC cells to radiation treatment and chemotherapy. Inhibition of miR-196a also altered cell cycle progression and induced G2/M arrest, which was related to changes in the levels of cyclin B1. ABCG2, which was highly expressed in untransfected EC cells, was inhibited by miR-196a knockdown. Thus, our results confirm the fact that miR-196a is highly involved in the biological behavior of EC progression in vitro. We conclude that miR-196a is a useful biological marker and potential therapeutic target for the clinical treatment of human EC.

Silencing of HIF-1α enhances the radiation sensitivity of human glioma growth in vitro and in vivo.

Gliomas are the leading cause of cancer-related mortality worldwide, and the incidence is increasing. Because gliomas often become resistant to radiation treatment, it is urgent to develop novel therapeutic methods that are more effective and less toxic than current therapies so as to enhance patient survival and quality of life. Effective enhancement of radiation therapy for gliomas in vivo and in vitro was observed upon silencing of hypoxia-inducible factor 1α (HIF-1α) with RNA interference; this enhancement was related to changes in the cell cycle and apoptosis that were accompanied by modulation of Cdc2, cyclin B1, and Bcl-2 expression. Our data suggest that HIF-1α silencing combined with radiation therapy will increase the therapeutic efficacy of glioma treatment via regulation of cell cycle and apoptosis-related signaling pathways.

Low-dose splenic radiation inhibits liver tumor development of rats through functional changes in CD4+CD25+Treg cells.

The increased number of CD4(+)CD25(+)Treg cells in tumor local and peripheral splenic tissues is related to the low immune function as well as to tumor recurrence and metastasis. Our pre-clinical studies showed that low-dose radiation (LDR) of the spleen in liver cancer patients significantly improves immune functions. However, the molecular mechanisms of such radiation remained ill defined. This study explores the role of CD4(+)CD25(+)Treg cells in radiation-induced immunomodulatory effects. Using the diethylnitrosamine (DEN)-induced rat liver tumor model and in vitro cell experiments, the percentage of CD4(+)CD25(+)Treg/CD4(+) cells in the blood and the expressions of Foxp3(+), IL-10, TGF-ß, and cytotoxic T lymphocyte-associated antigen-4(CTLA-4) in spleen and liver tumors significantly decreased after LDR of the spleen in rats with liver cancer. The tumors became smaller than those in the non-radiated group, with both showing a parallel relation. Flow cytometry and MTT results revealed that LDR failed to inhibit CD4(+)CD25(+)Treg cell proliferation. Conversely, apoptosis was reduced and proliferation was stimulated. This process also changed CTLA-4 molecule expression on the surfaces of CD4(+)CD25(+)Treg cells and reduced their inhibitory function against CD4(+)CD25(-)T cell proliferation, and the suppression function of CD4(+)CD25(+)Treg cells was further weakened with the introduction of the CTLA-4 inhibitor. Findings demonstrate that the reduction of CTLA-4 expression on the CD4(+)CD25(+)Treg cell surface and the further inhibition of cell function may be considered as important regulators of LDR-induced immunomodulatory effects. This study provides experimental evidence to elucidate the immune enhancement induced by this process and presents a novel method for liver cancer immunotherapy.

Electrochemical codeposition of vanadium oxide and polypyrrole for high-performance supercapacitor with high working voltage.

Electrochemical codeposition of vanadium oxide (V2O5) and polypyrrole (PPy) is conducted from vanadyl sulfate (VOSO4) and pyrrole in their aqueous solution to get V2O5-PPy composite, during which one-dimensional growth of polypyrrole (PPy) is directed. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) are used to characterize the composite, while scanning electron microscopy (SEM) is used to investigate their morphologies. Cyclic voltammetry (CV), chronopotentiometry (CP) for galvanostatic charge-discharge and electrochemical impedance spectroscopy (EIS) are used to study electrochemical activities and pseudocapacitive properties of the composite. The influences of VOSO4 to pyrrole ratio in the electro-codeposition solution on morphologies and pseudocapacitive properties of the composite are discussed. Due to the organic-inorganic synergistic effect, V2O5-PPy composite exhibits good charge-storage properties in a large potential window from -1.4 to 0.6 V vs SCE, with a specific capacitance of 412 F/g at 4.5 mA/cm(2). A model supercapacitor assembled by using the V2O5-PPy composite as the electrode materials displays a high operating voltage of 2 V and so a high energy density of 82 Wh/kg (at the power density of 800 W/kg).