Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

[Multi-sequence relation attention network for diagnosing HLA-B27-negative axial spondyloarthritis].

OBJECTIVE: To develop a new 3D multi-sequence relation attention network for exploring the complementary and correlation information of different magnetic resonance imaging (MRI) modalities and improving the diagnostic performance of HLA-B27-negative axial spondyloarthropathy (axSpA). METHODS: We retrospectively collected T1-weighted imaging (T1WI) and fat suppuration MRI (FS-MRI) data and clinical data of 375 HLA-B27-negative patients from the Third Affiliated Hospital of Southern Medical University (including 164 axSpA and 211 non-axSpA patients) and 49 patients from Nanhai Hospital (including 27 axSpA and 22 non-axSpA patients) between January, 2010 and August, 2021.A 3D relation attention network MSFANet based on multi-sequence MRI was used for automatic diagnosis of axSpA against non-axSpA in these patients.MSFANet consisted of a shallow shared feature learning module and a class-aware feature learning module, and latter module used a 3D multi-sequence relation attention mechanism to refine and fuse multi-sequence MRI features.A hybrid loss function was used to enhance the recognition ability of MSFANet by learning the loss weight coefficients of different branches to improve the classification performance. RESULTS: The experimental results demonstrated that MSFANet outperformed several state-of-the-art fusion algorithms (P<0.05) with AUC, accuracy, sensitivity, and specificity of 0.840, 77.93%, 83.70%, and 70.29% in the internal validation set, and of 0.783, 74.47%, 82.43% and 70.40% in the independent external validation set, respectively.The ablation studies showed that under the same architecture, the fusion model was superior to single-sequence models, which confirmed the effectiveness and necessity of fusing multi-sequence MRI.The visualization results demonstrated that MSFANet could focus on learning information from abnormal areas on MRI during the classification. CONCLUSION: We successfully constructed a 3D deep neural network based on multi-sequence MRI for differential diagnosis of HLA-B27-negative axSpA against nonaxSpA and verified the effectiveness of the multisequence relation attention mechanism for promoting classification performance of the network.

[A two-stitch continuous suture method for single-lumen ileostomy].

Objective: To explore the value of a two-stitch continuous suture in single- lumen ileostomy. Methods: This was a retrospective cohort study. Data for 98 patients who underwent single-lumen enterostomy were retrospectively collected between 1 January 2021 and 1 May 2022 at Zhujiang Hospital of Southern Medical University. All patients met the indications for prophylactic single-lumen ileostomy. Those older than 80 years of age, with complex underlying diseases, extremely poor systemic conditions who could not tolerate surgery, poor blood supply at the end of the bowel, and severe edema or severe infection at the end of the bowel were excluded. Among the included patients, patients who underwent surgery before 1 October 2021 underwent ileostomy with interrupted suture (control group, n=60), and patients operated on and after 1 October 2021 routinely underwent two-stitch continuous suture ileostomy (two-stitch stoma group, n=38). Two-stitch continuous suture ileostomy is performed as follows: the first continuous suture is used to suture the intestinal seromuscular layer, peritoneum, posterior sheath, and anterior sheath from deep to superficial layers. The bowel wall is then opened. The second continuous suture is used to suture the full thickness of the bowel and the skin. The differences in postoperative ostomy-related complications and operation time were compared between the groups. Results: There were no significant differences in baseline data between the groups (all, P>0.05). The operative time in the two-stitch stoma group was shorter than that of the control group (16.6±2.2 minutes vs. 25.1±2.4 minutes, respectively; t=-17.874;P<0.001). The incidences of mucocutaneous separation, dermatitis, and stoma rebound in the two-stitch stoma group were lower than those of the control group [5.3% (2/38) vs. 31.7% (19/60), χ2=9.633, P=0.002;5.3% (2/38) vs. 28.3% (17/60), χ2=7.923, P=0.005; and 2.6% (1/38) vs. 18.3% (11/60), P=0.026, respectively], while the incidences of parastomal hernia and stoma prolapse, and the postoperative visual analog scale scores in the two groups were similar (all P>0.05). Conclusion: Compared with traditional single-lumen ileostomy, two-stitch continuous suture ileostomy has the advantages of short operation time, simplicity, esthetic appearance of the stoma, and a significant reduction in the postoperative complications associated with ileostomy.

[Recommendations for the diagnosis and treatment of connective tissue disease-associated interstitial lung disease in China].

Interstitial lung disease (ILD) is a frequent complication of patients with connective tissue disease (CTD) and significantly affects morbidity and mortality. Disease course may vary from stable or mildly progressive to more severe, with rapid loss of lung function. At present, there are great challenges and poor prognosis in the diagnosis and treatment of CTD-ILD. Based on the evidence and guidelines from China and other countries, experts from the Chinese Rheumatology Association developed standardization of diagnosis and treatment of CTD-ILD. The aim is to strengthen the early identification of, standardize the diagnosis and treatment of CTD-ILD, and delay the progress of the disease.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

[Therapeutic effect of Panax notoginseng saponins combined with cyclophosphamide in mice bearing hepatocellular carcinoma H22 cell xenograft].

OBJECTIVE: To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft. METHODS: We examined the effects of treatment with different concentrations of PNS on H22 cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H22 cells. Mouse models bearing H22 cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate. RESULTS: Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H22 cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05). CONCLUSION: PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H22 tumor-bearing mice.

[Characteristics of CD8+ T cell infiltration in colorectal cancer and their correlation with prognosis].

Objective: As cytotoxic T cells, CD8+ T lymphocytes can kill tumor cells by releasing perforin and other effector molecules, but the correlation between their infiltration level and the prognosis of colorectal cancer varies in previous studies. This study aims to explore the distribution of CD8+T cells in tumor center and invasive margin of colorectal cancer, and to analyze their correlation with the prognosis of patients. Methods: A retrospective cohort study was used to analyze the clinicopathological features of 221 patients with colorectal cancer from the colorectal cancer pathological database of the Sixth Affiliated Hospital of Sun Yat-sen University between 2009 and 2012. Case inclusion criteria: (1) colorectal cancers confirmed by postoperative pathology; (2) patients with follow-up data. Exclusion criteria: (1) multiple primary cancers; (2) inflammatory bowel disease, Lynch syndrome or familial adenomatous polyposis; (3) no available paraffin slides; (4) patients receiving preoperative radiotherapy or chemotherapy. A total of 221 patients met the criteria. Immunohistochemical staining was used to count the CD8+ T cells in tumor center and invasive margin in the paraffin slides. Meanwhile the relative expression of CD8B gene in 22 fresh freeze samples of colorectal cancer was detected. Then the correlation of the expression with CD8+T cell density was examined. The patients were divided into high and low infiltration groups according to the level of CD8+T cells. Log-rank test was applied to compare the overall survival of the two groups of patients, and Cox regression analysis was used to adjust the prognostic significance of CD8+T cell infiltration. Results: There were 118 males and 103 females. In 221 slides, CD8+T cells infiltrating in invasive margin were more than those in tumor center [median (range): 37(0-141) / field vs. 14(0-106) / field, Z=-11.985, P<0.001], and the number of CD8+T cell in the tumor center was positively correlated with those in invasive margin (r=0.610, P<0.001). The number of CD8+ T cell in tumor center was positively correlated with the relative expression of CD8B gene (r=0.524, P=0.012). Survival analysis showed that the overall survival of the high infiltration group was better than that of the low infiltration group both in tumor center and invasive margin (median survival: 84.1 months vs. 73.5 months, P<0.001; 84.2 months vs. 75.9 months, P=0.002). Cox regression analysis revealed that high CD8+T cell infiltration in tumor center was an independent protective factor of overall survival (HR=0.369, 95% CI: 0.168-0.812, P=0.013). Conclusions: The infiltration level of CD8+T cells in tumor center is lower than that in invasive margin, and they are positively correlated. The level of CD8+ T cell infiltration in tumor center is related to overall survival and can be used as a potential pronostic marker.

[Establishment of index system for population based SARS-CoV-2 nucleic acid screening].

Objective: To establish an index system of population based SARS-CoV-2 nucleic acid screening, and provide reference to determine the screening coverage appropriately. Methods: The literature review and brain storming sessions were used to develop the basic frame and index system of population based SARS-CoV-2 nucleic acid screening. Based on Delphi method and Analytic Hierarchy Process, 21 domestic experts were selected for two rounds of consultation to determine the index system of population based SARS-CoV-2 nucleic acid screening and its weight. Results: The positive indexes of experts in two rounds of consultations were both 100%. The experts' authority coefficients (Cr) were 0.88±0.08 and 0.89±0.07, respectively. And the range of coefficient of variation (CV) were (0.08, 0.24), (0.09, 0.25). The Kendall's W coordination coefficients were 0.34 and 0.22 respectively, which were statistically significant. The index system of population based SARS-CoV-2 nucleic acid screening was established, which had 4 first-level indexes, 11 second-level indexes and 58 third-level indexes. Besides, the weight of each index was determined. Conclusion: The index system of population based SARS-CoV-2 nucleic acid screening has been established, which can provide scientific reference for the health administration to determine the coverage of population based SARS-CoV-2 nucleic acid screening when local COVID-19 epidemic occurs.

Long noncoding RNA OIP5-AS1 exhibits oncogenic activity in bladder cancer through miR-217 and MTDH.

OBJECTIVE: The aim of this study was to investigate the role of long non-coding Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in bladder cancer (BCa), and the mechanism of OIP5-AS1/microRNA-217 (miR-217)/metadherin (MTDH) in promoting the progression of BCa. PATIENTS AND METHODS: OIP5-AS1, miR-217 and MTDH expressions in BCa tissues and cells were detected by qRT-PCR or Western blot. CCK-8 and transwell assays were used to determine the proliferation and invasion of BCa cells. The correlation between OIP5-AS1 and miR-217, miR-217 and MTDH, and OIP5-AS1 and MTDH were studied by Luciferase reporter assay and Spearman correlation analysis. Statistical analysis of test data was performed using t-test. RESULTS: OIP5-AS1 was upregulated in BCa tissues and cells, and OIP5-AS1 knockdown could inhibit the proliferation and invasion of BCa cells. MiR-217 was a direct-acting target of OIP5-AS1, and MTDH was a target of miR-217. OIP5-AS1 knockdown inhibits human BCa cell proliferation and invasion through miR-217/MTDH axis. CONCLUSIONS: This study systematically explored the effect of OIP5-AS1 in human BCa. MiR-217/MTDH pathway mediated the promotion of OIP5-AS1 in BCa cells proliferation and invasion. OIP5-AS1, as an oncogene, could be used as a biomarker for the treatment of BCa.

[Construction and evaluation of dual-effect cord blood natural killer cells expressing highaffinity PD-1 and chimeric antigen CD19 receptor].

OBJECTIVE: To obtain novel dual-effect cord blood natural killer cells (CBNKCs) expressing high-affinity PD-1 (HAPD1) and chimeric antigen CD19 receptor (CAR) to improve the effect of CAR-based immunotherapy. METHODS: A dual-effect lentiviral vector expressing both HAPD1 and CAR targeting CD19 was constructed. CBNKCs were infected with the vector to obtain HAPD1 CAR19 CBNKCs. The surface markers of the cells including CD3-/CD16+CD56+, CD3+/CD16+CD56+, CD3+/CD4+, and CD3+/CD8+ were tested during cell proliferation. The cytotoxicity of CBNKCs, CAR19 CBNKCs and HAPD1 CAR19 CBNKCs incubated with CD19-positive target cells at the effector-target ratios of 5∶1, 10∶1 and 20∶1 was tested on days 7, 9, 12, and 15 of cell culture. The cytotoxicity of the cells against the target cells was also tested in NPG mice. RESULTS: CBNKCs were successfully transduced with T-cell designed CAR19 and HAPD1 CAR19 with an efficiency of (18.63±1.88)%. Infection with the lentiviral vector significantly reduced the cell expansion efficiency of the CBNKCs (10.97±2.77 vs 24.84±3.17, P < 0.05) but did not significantly affect the expressions of the surface markers (P>0.05). HAPD1 CAR CBNKCs showed stronger anti-tumor effect than CAR19 CBNKCs [(68.38±8.08)% vs (49.65±13.60)% at the effector-target ratios of 5∶1 and (79.11±7.42)% vs (59.78 ± 9.32)% at 10∶1; P < 0.05]. The infected CBNKCs showed the strongest cytotoxicity at 9 and 12 days after lentivirus infection. In the mouse models, transplantation of the dual-effect cells resulted in a significantly lower percentage of tumor cells in white blood cells than transplantation CAR-CBNKCs [(19.21 ± 3.07%) vs (29.08 ± 3.15)%, P < 0.05]. CONCLUSION: We obtained a novel dual-effect CBNKC co-expressing HAPD1 and CAR. The cells show strong cytotoxicity against the target tumor cells both in vitro and in vivo, which sheds light on a new strategy of immunotherapy against tumor cells.

CircRNF20 aggravates the progression of non-small-cell lung carcinoma by activating MAPK9.

OBJECTIVE: To explore the clinical significance of circRNF20 in non-small-cell lung carcinoma (NSCLC), and its regulatory effects on NSCLC cell functions by activating MAPK9. PATIENTS AND METHODS: Relative levels of circRNF20 and MAPK9 in NSCLC tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between circRNF20, MAPK9 and pathological factors in NSCLC patients was analyzed. Prognostic potentials of circRNF20 and MAPK9 in NSCLC were assessed by Kaplan-Meier method. The interaction between circRNF20 and MAPK9 was tested by Dual-Luciferase reporter assay. Regulatory effects of circRNF20 and MAPK9 on proliferative abilities in H358 and SPC-A1 cells were examined by Cell Counting Kit-8 (CCK-8) and colony formation assay. RESULTS: CircRNF20 and MAPK9 were upregulated in NSCLC tissues than normal ones. They were correlated to T stage and poor prognosis in NSCLC patients, while their levels were unrelated to gender, age, and incidences of lymphatic and distant metastasis. Knockdown of circRNF20 attenuated proliferative abilities in H358 and SPC-A1 cells. On the contrary, the overexpression of MAPK9 yielded the opposite results. MAPK9 was the target gene binding circRNF20, which was able to reverse the regulatory effect of circRNF20 on NSCLC proliferation. CONCLUSIONS: CircRNF20 and MAPK9 are upregulated in NSCLC cases, which are closely linked to T stage in NSCLC patients. They are independent prognostic factors for NSCLC. By activating MAPK9, circRNF20 stimulates NSCLC proliferation.

CircABCB10 silencing inhibits the cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis in rectal cancer.

Circular ATP binding cassette subfamily B member 10 (circABCB10) has been identified to have oncological functions in several tumors. However, the roles of circABCB10 in rectal cancer remain unknown. The expression of circABCB10, microRNA (miR)-326 and C-C motif chemokine ligand 5 (CCL5), and apoptosis related-protein was detected using quantitative real-time polymerase chain reaction or western blot, respectively. Cell survival or apoptosis was measured using cell counting kit-8 assay or flow cytometry. The accumulations of intracellular lipid reactive oxygen species (ROS) and Fe2+ were analyzed using C11-BODIP dye or iron kit assay, respectively. In vivo experiments were conducted using the murine xenograft model. The interaction between miR-326 and circABCB10 or CCL5 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. CircABCB10 and CCL5 were upregulated but miR-326 was downregulated in rectal cancer. The knockdown of circABCB10 promoted rectal cancer cell ferroptosis and apoptosis in vitro as well as inhibited tumor growth in vivo. miR-326 was a target of circABCB10, and the miR-326 inhibition could partially attenuate circABCB10 deletion-induced cell ferroptosis and apoptosis. miR-326 directly interacted with CCL5, and the miR-326 inhibition suppressed cell ferroptosis and apoptosis by targeting CCL5. Besides, we observed that miR-326 was negatively regulated by circABCB10, while CCL5 was positively regulated by it, and circABCB10 served as a sponge of miR-326 to regulate the CCL5 expression in rectal cancer cells. CircABCB10 silence promoted rectal cancer cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis, suggesting a potential therapeutic target for rectal cancer therapy.

[Progress and challenge of vaccine development against 2019-novel coronavirus (2019-nCoV)].

The outbreak of 2019-novel coronavirus (2019-nCoV) infection poses a serious threat to global public health. Vaccination is an effective way to prevent the epidemic of the virus. 2019-nCoV along with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) belong to the same ß-genus of coronavirus family. Basing on the previous experience and the technical platform of developing SARS-CoV and MERS-CoV vaccines, scientists from all over the world are working hard and quickly on the related fields. There are substantial progress in these fields including characterizing the 2019-nCoV virus, identification of candidate antigens and epitopes, establishment of animal models, characterizing the immune responses, and the design of vaccines. The development of 2019-nCoV vaccines covers all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, et al. As of March 2020, two 2019-nCoV vaccines have entered phase I clinical trials. One is named as Ad5-nCoV developed by the Chinese Institute of Biotechnology of the Academy of Military Medical Sciences and Tianjin Cansino Biotechnology Inc. Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein. The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein. Although the rapid development of 2019-nCoV vaccine, it still faces many unknown challenges, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine. The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated.

Effects of lncRNA SNHG20 on proliferation and apoptosis of non-small cell lung cancer cells through Wnt/ß-catenin signaling pathway.

OBJECTIVE: To investigate the influence of long non-coding ribonucleic acid (lncRNA) small nucleolar host gene 20 (SNHG20) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells through the Wnt/ß-catenin signaling pathway. PATIENTS AND METHODS: The human NSCLC cells were cultured and lncRNA SNHG20 was inhibited using si-SNHG20 and overexpressed using SNHG20-OE. Then, flow cytometry was used to detect the apoptotic rate. The targets of lncRNA SNHG20 were detected via dual-luciferase reporter gene assay, and the changes in the protein level were detected via Western blotting. RESULTS: LncRNA SNHG20 was highly expressed in the cancer tissues and serum of patients with NSCLC. LncRNA SNHG20 could promote the proliferation and inhibit the apoptosis of NSCLC cells. LncRNA SNHG20 could bind to micro RNA (miR)-197 in a targeted manner. Besides, nuclear translocation of ß-catenin was significantly enhanced after transfection of miR-197. After the down-regulation of miR-197 by small interfering RNA (siRNA), the key molecules TCF and LEF1 of the Wnt/ß-catenin pathway were significantly down-regulated. CONCLUSIONS: LncRNA SNHG20 promotes the proliferation and inhibits the apoptosis of NSCLC cells by targeting miR-197 through the Wnt/ß-catenin signaling pathway.

[Regulation of m

N^(6)-methyladenosine (m^(6)A) has been identified as a conserved epitranscriptomic modification of eukaryotic mRNAs, and plays important biological roles in the regulation of cellular metabolic processes. However, its role in myogenic differentiation is unclear. Here, we altered the m^(6)A RNA methylation level by overexpression of METTL3, and explored the effect of m^(6)A RNA methylation on myogenic differentiation of murine myoblasts in vitro. The m6A RNA methylation level is regulated by exogenous methylation inhibitor cycloleucine (Cyc) and methyl donor betaine (Bet). Therefore, chemical reagents of Cyc and Bet were used to test the regulatory effect of m^(6)A RNA methylation on myogenic differentiation. Results showed that METTL3 and Bet positively regulated the m^(6)A RNA methylation levels, and Cyc negatively regulated m^(6)A RNA methylation levels. In addition, m^(6)A methylation positively regulated myogenic differentiation in murine myoblasts. These findings provide insight in the mechanisms underlying the effect of m^(6)A RNA methylation on myogenesis.

Abatacept alleviates rheumatoid arthritis development by inhibiting migration of fibroblast-like synoviocytes via MAPK pathway.

OBJECTIVE: To investigate whether Abatacept could regulate the occurrence and progression of rheumatoid arthritis (RA) by mediating cell migration of fibroblast-like synoviocytes (FLS) via mitogen-activated protein kinase (MAPK) pathway. PATIENTS AND METHODS: Levels of MMP1, MMP3 and MMP13 in RA-FLS treated with Abatacept or MAPK pathway inhibitor were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The regulatory effect of Abatacept on MAPK pathway was detected by Western blot. Transwell assay was performed to access the role of Abatacept in regulating cell migration of RA-FLS. RESULTS: Abatacept treatment remarkably downregulated levels of MMP1, MMP3 and MMP13 in FLS, which were confirmed by qRT-PCR and ELISA. Migratory ability of FLS was inhibited by Abatacept treatment. Western blot results suggested that Abatacept treatment downregulated MAPK pathway-related genes in FLS. The effects of Abatacept on MMPs expressions and cell migration were partially reversed by SB203580 treatment, the MAPK pathway inhibitor. CONCLUSIONS: Abatacept inhibits FLS migration and MMPs expressions via inhibiting MAPK pathway, thereby inhibiting RA development.

Diagnostic values of serum IL-10 and IL-17 in rheumatoid arthritis and their correlation with serum 14-3-3η protein.

OBJECTIVE: This study aimed to investigate the diagnostic values of serum IL-10 and IL-17 in rheumatoid arthritis (RA) and their correlation with serum protein. PATIENTS AND METHODS: A retrospective analysis was performed on 116 RA patients admitted to the Yantaishan Hospital (the RA group) and 116 healthy subjects (the control group). Enzyme-linked immunosorbent assay was used to detect the expression levels of serum interleukin (IL)-10, IL-17 and 14-3-3η protein. Pearson analysis was performed to analyze the correlation between the expression levels of serum IL-10, IL-17 and 14-3-3η protein of patients in the RA group, and ROC curve analysis was conducted to measure the diagnostic values of IL-10, IL-17 and their combination in RA. RESULTS: Patients in the RA group had significantly lower serum IL-10 level and markedly higher IL-17 and 14-3-3η protein levels than those in the control group (p<0.001). Serum IL-10 level was negatively correlated with 14-3-3η protein level in RA patients (r=-0.582, p<0.001). Serum IL-17 level was positively correlated with 14-3-3η protein level in RA patients (r=0.482, p<0.001). Serum IL-10 level was negatively correlated with IL-17 level in RA patients (r=-0.468, p<0.001). The AUC of IL-10 for diagnosing RA was 0.671, with a 95% confidence interval of 0.602-0.741 and a cut-off value of 87.315. The AUC of IL-17 for diagnosing RA was 0.856, with a 95% confidence interval of 0.807-0.905 and a cut-off value of 87.844. The AUC of IL-10 combined with IL-17 for diagnosing RA was 0.887. CONCLUSIONS: RA patients had remarkably lower serum IL-10 level and significantly higher IL-17 and 14-3-3η protein levels than healthy people. IL-17 has better sensitivity and specificity than IL-10 for diagnosing RA. IL-10 combined with IL-17 is beneficial to improve the diagnostic level of RA, which provides the reference for the diagnosis, treatment and pathogenesis of RA.

[Efficacy and safety of monotherapy versus combination therapy in treatment of allergic rhinitis : a Meta-analysis].

Objective:To evaluate efficacy and safety of monotherapy versus combination therapy on allergic rhinitis（AR） in order to provide evidencebased reference for clinic drug treatment of AR.Method:The randomized controlled trials（RCT） about drug treatment of AR were searched in PubMed, Embase, Cochrane library, CNKI, WanFang Data. After screening the literatures, extracting the data and evaluating the quality, to compare total nasal symptom scores（TNSS）,composite symptom scores（CSS）,daytime nasal symptom scores（DNSS）,individual nasal symptom scores, total ocular symptom scores（TOSS）, daytime eye symptom scores（DESS）and incidence of adverse events（AE）between monotherapy group and combination therapy group. Meta-analysis was performed by RevMan 5.3 software.Result:A total of 12 RCTs were enrolled, 7 675 AR patients involved. The results of Metaanalysis showed that the efficacy of combination therapy group was superior to the monotherapy group in TNSS with significant difference（WMD=0.74,95%CI 0.31-1.17,P<0.05;WMD=1.40,95%CI0.98-1.82,P<0.05）.Compared with monotherapy group, individual nasal symptom scores in combination group were significantly decreased. There were no significant difference in incidence of AE（headache, dysgeusia, epistaxis） between two groups（RR=1.20,95%CI 0.87-1.65, P=0.28;RR=0.63,95%CI 0.31-1.24,P=0.18;RR=0.96,95%CI 0.63-1.64, P=0.85.Conclusion:Combination therapy can remarkably improve nasal symptom in AR patients compared with monotherapy, moreover, the incidence of AE between two groups were similar. We recommend combination therapy for allergic rhinitis.