Objective To investigate the expression level and clinical application value of circular RNA hsa_circ_0001766 in gastric cancer(GC)tissues and serum of patients with GC.Methods The PCR amplification products from GES-1 cells of normal gastric mucosa were analyzed for the cyclic sites of hsa_circ_0001766 by the Sanger sequencing technique.The expression levels of hsa_circ_0001766 in GES-1 cells treated or untreated with RNase R(RNase R)were detected by real-time fluorescence quantitative PCR(qRT-PCR).The expression levels of hsa_circ_0001766 in GC and adjacent tissues of 73 GC patients and serum samples of 34 GC patients were also detected by qRT-PCR.The receiver operating characteristics(ROC)curve was used to evaluate the clinical diag-nostic value of hsa_circ_0001766 in GC.The correlations between hsa_circ_0001766 and clinicopathological parameters in GC patients were also analyzed.Results There was cyclic sites in hsa_circ_0001766 and RNase R had no significant impact on the expression lev-el of hsa_circ_0001766 in GES-1 cells(t=1.678,P=0.169).Compared with adjacent tissues,the expression levels of hsa_circ_0001766 in GC tissues were significantly up-regulated(U=1 360,P<0.001).Compared with healthy controls,the expres-sion levels of hsa_circ_0001766 in serum of GC patients were significantly up-regulated(U=375,P<0.001).The area under the ROC curve(AUCROC),sensitivity,and specificity of hsa_circ_0001766 in GC tissues for diagnosing GC were 0.759(95％CI:0.682-0.837,P<0.000 1),79.45％,and 68.49％,respectively.The AUCROC,sensitivity,and specificity of serum hsa_circ_0001766 in diagnosing GC were 0.773(95％CI:0.662-0.884,P<0.000 1),73.53％,and 72.12％,respectively.The expression levels of hsa_circ_0001766 in GC tissues were correlated with lymph node metastasis(x2=5.509,P=0.019)and TNM staging(x2=5.161,P=0.023).The 3-year survival rate of GC patients with high expression of hsa_circ_0001766 in GC tissues was significantly lower than that with low ex-pression(x2=3.700,P=0.037).Conclusion The hsa_circ_0001766 in GC tissues and serum of GC patients is highly expressed,and its change in the expression level is of great significance for the diagnosis and prognostic evaluation of GC patients.

Objective To investigate the expression level and clinical application value of circular RNA hsa_circ_0001766 in gastric cancer(GC)tissues and serum of patients with GC.Methods The PCR amplification products from GES-1 cells of normal gastric mucosa were analyzed for the cyclic sites of hsa_circ_0001766 by the Sanger sequencing technique.The expression levels of hsa_circ_0001766 in GES-1 cells treated or untreated with RNase R(RNase R)were detected by real-time fluorescence quantitative PCR(qRT-PCR).The expression levels of hsa_circ_0001766 in GC and adjacent tissues of 73 GC patients and serum samples of 34 GC patients were also detected by qRT-PCR.The receiver operating characteristics(ROC)curve was used to evaluate the clinical diag-nostic value of hsa_circ_0001766 in GC.The correlations between hsa_circ_0001766 and clinicopathological parameters in GC patients were also analyzed.Results There was cyclic sites in hsa_circ_0001766 and RNase R had no significant impact on the expression lev-el of hsa_circ_0001766 in GES-1 cells(t=1.678,P=0.169).Compared with adjacent tissues,the expression levels of hsa_circ_0001766 in GC tissues were significantly up-regulated(U=1 360,P<0.001).Compared with healthy controls,the expres-sion levels of hsa_circ_0001766 in serum of GC patients were significantly up-regulated(U=375,P<0.001).The area under the ROC curve(AUCROC),sensitivity,and specificity of hsa_circ_0001766 in GC tissues for diagnosing GC were 0.759(95％CI:0.682-0.837,P<0.000 1),79.45％,and 68.49％,respectively.The AUCROC,sensitivity,and specificity of serum hsa_circ_0001766 in diagnosing GC were 0.773(95％CI:0.662-0.884,P<0.000 1),73.53％,and 72.12％,respectively.The expression levels of hsa_circ_0001766 in GC tissues were correlated with lymph node metastasis(x2=5.509,P=0.019)and TNM staging(x2=5.161,P=0.023).The 3-year survival rate of GC patients with high expression of hsa_circ_0001766 in GC tissues was significantly lower than that with low ex-pression(x2=3.700,P=0.037).Conclusion The hsa_circ_0001766 in GC tissues and serum of GC patients is highly expressed,and its change in the expression level is of great significance for the diagnosis and prognostic evaluation of GC patients.

A patient aged 68 years old presented urinary frequency, urgency, and gross hematuria for 1 month, with initial PSA of 72.72 ng/ml and alkaline phosphatase (ALP)of 114 U/L. Prostate biopsy pathology showed small cell neuroendocrine carcinoma of prostate. The patient was immediately administered 6 cycle of chemotherapy including etoposide and cisplatin combined with medical castration. The CDK4 gene was detected 1.99 times amplification by peripheral blood free DNA (cfDNA)gene analysis. The chemotherapy was followed by parbosini therapy. The number and density of bone metastases continued to decrease significantly by bone scan at 3 and 6 months after treatment, with a continuous decline of ALP and PSA. After 1 year of follow-up, pelvic MRI and bone systemic imaging indicated stable lesions, with PSA of 0.05 ng/ml and ALP of 59 U/L.

Objective:To evaluate the clinical efficacy of kidney-invigorating and asthma-relieving granules in treating kidney deficiency type of bronchial asthma patients in persistent.Methods:A total of 100 patients with bronchial asthma admitted to Shanghai Municipal Hospital of TCM from March 2020 to August 2020 were selected as the research subjects. The patients were divided into control group and treatment group by random and double blind method, 50 in each group. Both groups were treated by routine basic treatment. The control group was treated with Kidney-invigorating and asthma-relieving Placebo, while the observation group was treated with kidney-invigorating and asthma-relieving granules. All the treatment lasted for 6 weeks. The TCM syndromes scores, Asthma Control Test (ACT) scores, Peak expiratory flow/predicted value (PEF%) and eosinophil in peripheral blood before and after treatment were observed.Results:A total of 91 patients completed the clinical study. There were 45 patients in the control group and 46 in the treatment group. The total effective rate in the treatment group was 93.5% (43/46), while that in the control group was 77.8% (35/45), and the difference was statistically significant ( χ2=4.579, P=0.032). After the treatment, the scores of integral efficacy on syndromes in Chinese medicine, ACT and PEF% in the treatment group were significantly higher than those in the control group ( t values were 2.802, 3.420 and 8.938, respectively, all Ps<0.01). The eosinophil in peripheral blood of patients in the treatment group was significantly lower than that of the control group ( t=3.481, P=0.001). Conclusion:On the basis of conventional treatment of western medicine, kidney-invigorating and asthma-relieving granules can relieve the clinical symptoms of asthma, improve the control level of asthma, enhance the level of PEF, reduce airway inflammation.

Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.

Objective To investigate the multiple risk factors for lower extremity lymphedema in patients following treatment of common gynecologic cancers by meta-analysis for systematic analysis and comprehensive quantitative study.Methods Clinical trials published up until August 2016 were retrieved from PubMed, Embase, and the Cochrane Library.The quality of the included studies was assessed by the Newcastle-Ottawa Scale, and data analysis was performed using Stata 14.0 and RevMan 5.3.The strength of the associations between risk factors and gynecologic cancer-related lower extremity lymphedema was described as odds ratio (OR) and 95% confidence intervals (CI).Results Eighteen studies were included in the meta-analysis, and 8 relevant factors were identified.The risk factors for lower extremity lymphedema after treatment of gynecologic cancer mainly included radiotherapy (OR=2.45, 95%CI:2.05-2.95, P=0.000), FIGO stage (OR=2.29, 95%CI:1.66-3.14, P=0.000), and pelvic lymph node dissection (OR=2.00, 95%CI:1.02-3.91, P=0.040).Conclusions Radiotherapy, FIGO stage, and pelvic lymph node dissection are the main risk factors for lower extremity lymphedema after treatment of gynecologic cancers.

Background: The mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer (CRC) is limited. Synthetic lethality arises with a combination of two or more separate gene mutations that causes cell death, whereas individual mutations keep cells alive. This study aimed to identify the genes responsible for resistance to trametinib in CRC cells, using a synthetic lethal short hairpin RNA (shRNA) screening approach. Methods: We infected HT29 cells with a pooled lentiviral shRNA library and applied next-generation sequencing to identify shRNAs with reduced abundance after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in validation studies. Stable ring finger protein 183 (RNF183)-overexpressing cell lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF183-knockdown cell lines were generated by infection of lentivi-ruses that express RNF183 shRNA, and small interference RNA (siRNA) was used to knock down RNF183 transiently. Quantitative real-time PCR was used to determine the mRNA expression. Western blotting, immunohistochemical analysis, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the protein abundance. MTT assay, colony formation assay, and subcutaneous xenograft tumor growth model were used to evaluate cell proliferation. Results: In the primary screening, we found that the abundance of RNF183 shRNA was markedly reduced after treatment with trametinib. Trametinib induced the expression of RNF183, which conferred resistance to drug-induced cell growth repression and apoptotic and non-apoptotic cell deaths. Moreover, interleukin-8 (IL-8) was a downstream gene of RNF183 and was required for the function of RNF183 in facilitating cell growth. Additionally, elevated RNF183 expression partly reduced the inhibitory effect of trametinib on IL-8 expression. Finally, xenograft tumor model showed the synergism of RNF183 knockdown and trametinib in repressing the growth of CRC cells in vivo. Conclusion: The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.

Objective To identify the clinicopathological factors affecting the number of lymph nodes yielded from specimens obtained by laparoscopic?assissted resection of rectal cancer, and discuss further the possible causes of insufficient lymph nodes retrieval (<12) . Methods The clinicopathological data of 422 consecutive rectal cancer cases, who underwent radical laparoscopic rectal resection ( R0) at our department during January to October 2015, were analyzed retrospectively. The correlation between the clinicopathological factors and the number of lymph nodes yielded from the surgical specimens was assessed statistically. Results Age of the patient, length of specimen, tumor size and operating surgeon were significantly associated with the lymph node yield ( all P<0.05) . The total number of lymph nodes yielded in 351 patients without neoadjuvant therapy ranged 8?49, with an average of 22. 5, and the lymph node metastasis rate was 0?100% with an average of 7.6%.The total number of lymph nodes yielded from the 71 patients receiving neoadjuvant therapy ranged 9?70, with an average of 18.3, and the lymph node metastasis rate was 0?73. 0%, with an average of 7. 6%. Neoadjuvant therapy decreased the total lymph node yield obviously (P<0.001), but didn′t decrease the lymph node metastasis rate (P=0.636).Of all the patients investigated, 19 cases had less than 12 dissected lymph nodes, and 403 cases had at least 12 lymph nodes removed. Gender, tumor size and neoadjvant therapy were independent risk factors for yield of twelve or more lymph nodes (all P<0.05). Conclusions Age of the patient, length of specimen, tumor size, operating surgeons and neoadjuvant therapy are significantly correlated with the total number of lymph nodes yielded from laparoscopically resected specimens of rectal cancer. Neoadjvant therapy may obviously decrease the number of yielded lymph nodes, while not decreases the lymph node metastasis rate. Male gender, small size of the tumor, and neoadjvant therapy are possible risk factors for harvesting less than 12 lymph nodes.

Objective To identify the clinicopathological factors affecting the number of lymph nodes yielded from specimens obtained by laparoscopic?assissted resection of rectal cancer, and discuss further the possible causes of insufficient lymph nodes retrieval (<12) . Methods The clinicopathological data of 422 consecutive rectal cancer cases, who underwent radical laparoscopic rectal resection ( R0) at our department during January to October 2015, were analyzed retrospectively. The correlation between the clinicopathological factors and the number of lymph nodes yielded from the surgical specimens was assessed statistically. Results Age of the patient, length of specimen, tumor size and operating surgeon were significantly associated with the lymph node yield ( all P<0.05) . The total number of lymph nodes yielded in 351 patients without neoadjuvant therapy ranged 8?49, with an average of 22. 5, and the lymph node metastasis rate was 0?100% with an average of 7.6%.The total number of lymph nodes yielded from the 71 patients receiving neoadjuvant therapy ranged 9?70, with an average of 18.3, and the lymph node metastasis rate was 0?73. 0%, with an average of 7. 6%. Neoadjuvant therapy decreased the total lymph node yield obviously (P<0.001), but didn′t decrease the lymph node metastasis rate (P=0.636).Of all the patients investigated, 19 cases had less than 12 dissected lymph nodes, and 403 cases had at least 12 lymph nodes removed. Gender, tumor size and neoadjvant therapy were independent risk factors for yield of twelve or more lymph nodes (all P<0.05). Conclusions Age of the patient, length of specimen, tumor size, operating surgeons and neoadjuvant therapy are significantly correlated with the total number of lymph nodes yielded from laparoscopically resected specimens of rectal cancer. Neoadjvant therapy may obviously decrease the number of yielded lymph nodes, while not decreases the lymph node metastasis rate. Male gender, small size of the tumor, and neoadjvant therapy are possible risk factors for harvesting less than 12 lymph nodes.

OBJECTIVETo evaluate the early hematologic, cytogenetic and molecular responses in newly diagnosed patients with chronic myelogenous leukemia in chronic phase（CML-CP）and initially treated with a generic imatinib（Xinwei）, manufactured by Jiansu Hansoh Pharmaceutical Group Co., Ltd.

METHODS107 newly diagnosed patients of CML-CP, whose ages were above 18- year- old and who had never received any tyrosine kinase inhibitor（TKI）were treated with Xinwei 400 mg QD. The hematologic, cytogenetic and molecular responses were assessed at 3- and 6-month, and adverse effects were evaluated throughout the study.

RESULTS107 patients were treated with Xinwei for at least 3 months, 54 of them were treated for 6 months or more. At 3- month, the complete hematologic responses（CHR）rate were 98.1%（105/107）; 47/57（82.5%） patients achieved major cytogenetic response（MCyR）, and 20/57 （35.1%） patients complete cytogenetic response（CCyR）; BCR- ABLIS was ≤10% in 77/106 patients （72.6%）, 11 of them（10.4%）achieved major molecular response（MMR, BCR-ABLIS was ≤0.1%）. At 6-month, the CHR rate was 100%（54/54）; 28/39 patients（71.8%）achieved CCyR; BCR-ABLIS was ≤1% in 37/54 patients （68.5% ）, 18 of them （33.3% ） achieved MMR. The grade Ⅲ leukopenia, thrombocytopenia and anemia rates were 19.5%, 23.0% and 13.8%, respectively. No grade Ⅳ hematologic toxicity occurred. The common non- hematologic toxicities were edema（74.7%）, nausea（48.3%）, bone pain（42.5%）, rash（36.8%）, diarrhea（34.5%）, fever（23.0%）, cramp（11.5%）and impaired liver function （3.4%）. No patient experienced grade Ⅳ non- hematologic toxicity. No adverse effects related death occurred.

CONCLUSIONOur results revealed the excellent early haematology, cytogenetic and molecular responses and safety of Xinwei in treating patients with CML-CP.

Anemia ; Antineoplastic Combined Chemotherapy Protocols ; Cytogenetics ; Drugs, Generic ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Prospective Studies ; Protein Kinase Inhibitors ; Remission Induction ; Thrombocytopenia ; Treatment Outcome