OBJECTIVE:Exercise intervention is one of the main treatments for fibromyalgia,but there is no consistent conclusion on the choice of different exercise modalities.In this article,a network Meta-analysis was used to comprehensively and quantitatively evaluate the effects of different exercise modalities on fibromyalgia syndrome. METHODS:PubMed,EMbase,Scoups,The Cochrane Library,Web of Science,CNKI,WanFang Database,and China Biomedical Literature Database were searched for relevant literature,with a search timeframe from the establishment of each database to June 2023.The outcome indicators included five continuous variables,including fibromyalgia impact questionnaire-revised(FIQ)scores,visual analogue scale(VAS)scores,quality of life,quality of sleep,and depression.The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the included literature.RevMan 5.4 software was used to perform effect sizes,subgroup analyses,and sensitivity analyses of the data.Stata 17 software was used to perform reticulation and network Meta-analysis of the data. RESULTS:A total of 13 articles with 14 randomized controlled trials were finally included.The overall methodological quality of the literature was high.The results of traditional Meta-analysis showed that,compared with the control group,exercise therapy significantly improved the FIQ score[standardized mean difference(SMD)=-0.67,95％confidence interval(CI):-0.83 to-0.50,P<0.01],VAS score(SMD=-0.72,95％CI:-0.90 to-0.54,P<0.01),quality of life(SMD=1.03,95％CI:0.45 to 1.61,P=0.000 5),sleep quality(SMD=-0.62,95％CI:-0.98 to-0.25,P=0.001),and depression(SMD=-0.63,95％CI:-1.09 to-0.18,P=0.007).Network Meta-analysis showed that the probability of optimal intervention effect of exercise modalities on FIQ scores was ranked as:mind-body exercise(86.5)>resistance exercise(70.5)>aerobic exercise(41.7);the probability of optimal intervention effect of exercise modalities on VAS scores was ranked as:resistance exercise(85.3)>mind-body exercise(74.3)>aerobic exercise(34.5). CONCLUSION:Exercise therapy significantly improves FIQ scores,VAS scores,quality of life,sleep quality,and depression in patients with fibromyalgia syndrome.Mind-body exercise and resistance exercise are the most effective exercise modalities to reduce FIQ scores and VAS scores in patients with fibromyalgia syndrome.

Objective: To investigate the application of single-molecule PCR (SM-PCR) in the detection of plasma ctDNA for the treat-ment of patients with advanced lung adenocarcinoma. Methods: In total, 30 patients diagnosed with advanced lung adenocarcinoma were enrolled between June 2017 and May 2018. ctDNA fragments of the target genes (EGFR, KRAS, BRAF, ALK, HER2, and TP53) from the blood samples were enriched by SM-PCR, and DNA libraries were prepared. Finally, a high-throughput sequencing was performed. The EGFR detection of tumor tissue samples was performed using real-time fluorescence PCR based on the amplification refractory mutation system (ARMS) and consistency in the results of EGFR mutation detection in the plasma and tissue was compared. Results:The results of both the methods were consistent (Kappa=0.867, P<0.001). The McNemar's test also indicated that the results are not statistically different (P=0.500). Conclusions: SM-PCR can be used for the detection of plasma EGFR mutations. The target detection sites are more comprehensive and multiple mutations can be detected at the same time. Results of the analysis are more precise and can be absolutely quantified.

Objective:To study the effects of IL-8 on the polarization of monocytes and the effects of IL-8-induced tumor-associated macrophages(TAMs)on the invasion and metastasis of hepatocellular carcinoma(HCC).Methods:After exogenous IL-8 stimulation of THP-1 cells for 72h,the percentages of M1 and M2 TAMs were examined.RT-PCR and Western blot assays were used to study epitheli-al-mesenchymal transition(EMT),and wound-healing and transwell assays were preformed to study the invasion potential of HCC cells after co-culturing with TAMs and HCC cell lines in vitro.Lastly,100 cases of HCC tissue samples were used to validate the correlation among TAM numbers,IL-8,and EMT features of HCC cells via immunohistochemistry(IHC)staining methods.Results:Exogenous IL-8 induced significant M2 polarization of TAMs in THP-1 cells.TAMs further promoted EMT in HCC and enhanced the invasion potential of HCC in vitro.Finally,significant positive correlations among the numbers of TAMs,IL-8 expression,and N-cadherin expression were identified in primary HCC tissue samples(r=0.22,r=0.20,P<0.05).Conclusions:IL-8 locally attracted and activated TAMs,and promot-ed M2 polarization of TAMs,which further promoted the EMT and invasion potential of HCC cells both in vitro and in vivo.

Objective: To detect eight highly related driver genes in non-small cell lung cancer (NSCLC), and to analyze the relationship between gene variations and clinical-pathological features. Methods: We collected 212 NSCLC samples from Tianjin Medical University Cancer Institute and Hospital, and sequenced eight genes which are EGFR, KRAS, BRAF, ALK, MET, ERBB2, ROS1 and RET. Results: EGFR gene variation rate was as high as 52.8%, followed by KRAS (8.5%), ALK (8.0%), ERBB2 (6.1%), MET (3.8%), BRAF (1.4%), RET (0.9%) and ROS1 (0.9%) in eight detecting genes, at least one driver gene variant was detected in 75% samples, and driver gene variant showed strong mutual exclusion. The most common EGFR mutations were 19 exon deletion and L858R mutation, and the mutation of EGFR T790M was accompanied by the above two mutations. The proportion of non-EGFR T790M mutations in patients with exon 19 dele-tion was lower than that of L858R mutations (P=0.04). There were 15.2% patients with EGFR mutation accompanied by EGFR amplifica-tion, and the proportion of patients with EGFR mutation frequency greater than 40% with EGFR amplification was higher than that without EGFR amplification (P<0.01). Women, non-smoking, patients with adenocarcinoma were prone to carry EGFR especially EGFR sensitive mutations (P<0.01). Patients with lung adenocarcinoma (P=0.013), late clinical stage (P=0.048), and lymph node metastasis (P=0.027) had a higher proportion of EGFR amplification. The incidence of KRAS mutation was higher in men, left lung cancer and smoking patients (P=0.009, P=0.048, P=0.037). Patients with non-KRAS mutations, ALK fusions were younger (P=0.005, P=0.031), and with KRAS mutations were older (P=0.055). Conclusions: Next-generation sequencing (NGS) can simultaneously detect eight highly re-lated driver genes in NSCLC patients to provide evidence for clinicians. NGS based on detection of multiple genes provides more possi- bilities for individualized diagnosis and treatment of NSCLC.

Breast cancer is the most common malignant tumor in women. With the development of cell biology and molecular bio-technology, great progress has been made in the study of the pathogenesis of breast cancer. Familial breast cancer is closely related to the mutation of susceptible genes. Selected susceptible genes of breast cancer can be grouped into three categories: high-, medium-, and low-penetrance susceptible genes. The means of identifying the high-risk sites of pathogenic mutation and genetic polymorphism is the focus of research on the genetic predisposition of breast cancer.

Objective: To investigate the immunosuppressive effect and underlying molecular mechanisms of Myeloid-derived suppressor cells (MDSCs) on T cells activity through IL-6activatingSTAT3/IDO signaling pathway. Methods: Twenty pairs of cancer tissues and the corresponding adjacent normal tissues from breast cancer patients treated at Tianjin Medical University Cancer Institute and Hospital from November 2015 to February 2016 were collected for this study; in the meanwhile, peripheral blood samples from 40 healthy donorswere also collected. CD33+ cells in tumor tissues and CD33+ CD14 + cells in peripheral blood of helthy donors were sorted out with MicroBeads technology. CD33+ cells were in vitro co-cultured with breast cancer cell line MDA-MB-231 to induce MDSCs. Flow cytometry was used to detect the proportion of CD45+ CD13+CD33+CD14-CD15- MDSCs.Western Blotting was used to detect the expression ofSOCS1，SOCS3, JAK1, JAK2, TYK2, STAT1, STAT3 and their phosphorylation levels. qRT-PCR was used to detect the expression of IL-6 and SOCS1-3. CCK8 was used to detect the T cell proliferation. Annexin V staining was used to detect T cell apoptosis. ELISA was used to detect IL-10 and IFN-γ secreted by T cells. Results: There were MDSCs infiltration in all 20 cases of breast cancer tissues for different levels (15.3%~58.1%), with a mean level of (29.82± 11.46%); the infiltration of IL-6high group was significantly higher than that of the IL-6low group [（13.75±3.44） % vs（4.31±1.50） %， P< 0.05], indicating that IL-6 expression was positively correlated with MDSCs infiltration (R2=0.4399, P<0.01). In vitro experiments showed that tumor-derived IL-6 significantly promoted the generation and immunosuppressive activity of MDSCs (P<0.05), which could be reversed by the blocking of IL-6. In the meanwhile, the expression of SOCS3 in MDSCs that induced in vitro was absent, which can be inhibited by blocking IL-6 (P<0.05). Conclusion: The study has demonstrated that tumor-derived IL-6 stimulates the continuous activation of the JAK/STAT signaling pathway and the absence of SOCS3 expression in MDSCs, thereby promoting the infiltration, generation and immunological activity of MDSCs. Therefore, IL-6 signaling pathway can be used as therapeutic target to weaken MDSCs generation and reverse MDSCs activity.

Objective:To investigate the function of breast cancer susceptibility gene variants in predicting breast cancer risk and guid-ing clinical treatment through DNA sequencing. Methods:This study involved 146 patients, 71 high-risk cases, and 55 healthy people, totaling 272 cases. The subjects were treated in Tianjin Medical University Cancer Institute and Hospital from November 2013 to July 2015. Genomic DNA was sequenced by a second generation sequencing platform. All exon areas of six common breast cancer suscepti-bility genes (BRCA1, BRCA2, PTEN, STK11, TP53, and RAP1) were sequenced through amplicon sequencing method. Meaningful vari-ants including single nucleotide variants (SNVs), insertion-deletions (InDels) and nonsense mutations were selected and statistical methods, such as t test andχ2 test, were used to analyze the statistical differences in incidence rates among three groups. Results:A total of 177 meaningful variants were confirmed, including 50 SNVs, 8 nonsense mutations, and 9 InDels. Among the variants, 31 were recorded in the Exome Aggregation Consortium (ExAC), 40 were noted in ClinVar database, and 21 were not encoded in the present da-tabase, which were defined as new variants in this study. Conversely, 57 variants (85.1%) were found in breast cancer patients and high-risk cases, and the incidence of axillary lymph node metastasis (P=0.010) and pathological stages (P=0.002) in mutation positive patients were both higher than mutation negative patients. Moreover, the percentage of family history of cancer (P=0.005) and triple negative breast cancer (P=0.009) were both higher in patients carrying pathogenic mutations than in nonpathogenic patients. Conclu-sion:Breast cancer susceptibility gene variants may not only be a tool used to predict the risk of getting breast cancer but also a mean-ingful guideline for the clinical treatment and prognosis evaluation.

OBJECTIVETo introduce the recent developments in cancer immunoinformatics with an emphasis on the latest trends and future direction.

DATA SOURCESAll related articles in this review were searched from PubMed published in English from 1992 to 2013. The search terms were cancer, immunoinformatics, immunological databases, and computational vaccinology.

STUDY SELECTIONOriginal articles and reviews those were related to application of cancer immunoinformatics about tumor basic and clinical research were selected.

RESULTSCancer immunoinformatics has been widely researched and applied in a series of fields of cancer research, including computational tools for cancer, cancer immunological databases, computational vaccinology, and cancer diagnostic workflows. Furthermore, the improvement of its theory and technology brings an enlightening insight into understanding and researching cancer and helps expound more deep and complete mechanisms of tumorigenesis and progression.

CONCLUSIONCancer immunoinformatics provides promising methods and novel strategies for the discovery and development of tumor basic and clinical research.

Objective:To explore the status of STAT3 phosphorylation in myeloid-derived suppressor cells (MDSCs) of breast cancer and its function in the immunosuppressive effect of MDSCs on proliferation and cytokine secretion of T cells. Methods:CCD33+cells were isolated from healthy umbilical cord, blood-derived, peripheral blood mononuclear cells and were co-cultured with breast cancer cell line MDA-MB-231 in vitro using Transwell plates to induce MDSCs. The untreated CD33+cells were used as con-trols. Idoxuridine (IDO) suppressor expression and STAT3 phosphorylation were examined using Western blot assay. The proliferation and cytokine secretion of T cells, which were co-cultured with MDSCs, were determined by methyl thiazol tetrazolium assay and en-zyme-linked immunosorbent assay. 1-MT and JSI-124 were used to investigate the function of IDO and pSTAT3 in MDSC-mediated T cell immunosuppression. Results:The protein levels of IDO and pSTAT3 in MDSCs were significantly upregulated. MDSCs obviously suppressed T-cell proliferation, which was reversed by 1-MT or JSI-124 (P<0.05). MDSCs could promote TGF-βand IL-10 secretions, but could also remarkably inhibit IFN-γsecretion (P<0.05). After incubation with 1-MT or JSI-124, the increase in TGF-βand IL-10, as well as the decrease in IFN-γ, was significantly reversed. Conclusion:The upregulated pSTAT3 induced the IDO increase in MDSCs. JSI-124 can block MDSC-mediated immunosuppressive effect on T cells in breast cancer.

Objective: To investigate the effect of RetroNectin on CIKs cells and the related mechanisms. Methods: Peripheral blood mononuclear cells (PBMC) were collected from patients and divided into two groups: group Ⅰ and group Ⅱ. Samples in group Ⅰ were seeded into culture flask precoated with RetreNec-tin and CD3mAb to induce CIKs. While samples in group Ⅱ were seeded into common culture flask. The pro-liferation of CIKs was detected by cytometric analysis. The cytotoxic activity of CIKs was determined by LDH assays. The phenotype changes and cell cycle of CIKs were identified by flow cytometry. The apoptosis of cells was detected by Annexin V/PI. Western blot was employed to detect the level of protein Vav1. The CD49d and CD49e were blocked by anti-CD49d and anti-CD49e and the proliferation of cells was tested by cytometric analysis after the blockage. The phenotype changes of cells were identified by flow cytometry after the blockage. Results: RetroNectin enhanced the proliferation of CIKs (P<0.05). Flow cytometric analysis showed that RetroNectin significantly increased the number of CD25+ T cells (P<0.05). RN-CIK was more ac-tive than CIK in killing HCT-8 cell lines in vitro (P<0.05). RetroNectin could block the CIKs at G_1 phase (P<0.05) and resist apoptosis. There was no significant difference in the proliferation between the two groups af-ter the blockage with CD49d and CD49e (P>0.05). The expression of protein Vavl was associated with CD25+T cells. Conclusion: RetroNectin enhances the proliferation of CIKs by influencing the cell cycle, resist-ing apoptosis possibly through the site of CD49d and CD49e, and inducing T cell activation as the second sig-naling through Vav1.