Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective:To explore the relationship between adipocytokine levels in bone marrow and the onset,progression,and prognosis of myelodysplastic syndromes(MDS).Methods:Retrospective analysis of adipocytokine levels in the bone marrow of 72 patients with MDS and 16 patients with MDS-related secondary acute myeloid leukemia(sAML),including adiponectin(ADP),leptin(LEP),visfatin/nicotinamide phosphoribosyltransferase(NAMPT),adipsin/complement factor D(CFD),and C1q/TNF-related protein 1(CTRP1),detected by enzyme-linked immunosorbent assay(ELISA)at The Affiliated Cancer Hospital of Zhengzhou University from February 2020 to February 2022.High-throughput sequencing was used to detect MDS-related genes in 70 patients and the relationship between adipocytokines and the clinical characteristics,disease subtypes,mutant genes,and prognosis of patients were analyzed.Seventy-eight MDS-related genes were identified.Results:Clinical characteristics showed that ADP(P=0.027)and LEP(P=0.019)levels were significantly lower in men than inwomen;ADP(P=0.020),CFD(P<0.001),and NAMPT(P=0.021)levels were significantly lower in patients aged<65 years than in patients aged≥65,where-as LEP levels were significantly higher(P=0.043).Adiponectin levels were significantly higher in patients with BMI<24 than in patients with BMI≥24(P=0.025),whereas LEP levels were significantly lower(P=0.020);NAMPT levels were significantly higher in the group with in-creased blasts than in the group with no blasts(P=0.037).The CTRP1 levels were significantly higher in the MDS group than in the sAML group(P=0.010).Abnormal gene correlation analysis showed that elevated CTRP1 levels were positively correlated with the occurrence of epigenetically related abnormal genes(P=0.001)and were positively correlated with the occurrence of TET2 and U2AF1(P<0.001 and P=0.036,respectively);ADP and CFD levels were positively correlated with the occurrence of NPM1(P=0.048 and P=0.026,respectively).Multifactorial Cox proportional hazards regression model analysis showed that LEP<0.2 ng/mL was an independent risk factor for progres-sion-free survival(PFS)and overall survival in patients with MDS(P=0.002 and P<0.001,respectively),whereas NAMPT<2.1 ng/mL was a protective factor for PFS in patients with MDS(P=0.043).Conclusions:Adipocytokines in the bone marrow microenvironment are closely as-sociated with the clinical characteristics,gene mutations,and prognosis of patients with MDS,with LEP<0.2 ng/mL being an independent prognostic risk factor and NAMPT<2.1 ng/mL being a prognostic protective factor.

Objective? To explore the effects of "1+N" extended nursing on medication compliance, self-management ability and metabolic indicators among discharged type 2 diabetes patients. Methods? From October to December 2017, we selected 300 discharged type 2 diabetes patients from Department of Endocrinology from Shaanxi Provincial People's Hospital as subjects. All of the patients were divided into intervention group and control group with the method of random number table, 150 cases in each group. Control group carried out telephone follow-up post discharge. On the basis of telephone follow-up, intervention group implemented "1+N" extended nursing. We compared the fasting blood glucose (FBG), bisphosphoglyceric acid (BPG), glycosylated hemoglobin (HbA1c), body mass index (BMI), scores of 8-item Morisky Medication Adherence Scale (MMAS-8) and the scoring rate of Diabetes Self-care Scale (2-DSCS) of patients between two groups 6 months after follow-up. Results? After intervention, the FBG, BPG and BMI of intervention group were lower than those of control group with statistical differences (P＜0.05). The number of patients with the high level of compliance of MMAS-8 in intervention group was more than that in control group with a statistical difference (P＜0.05).The item scoring rate of 2-DSCS of patients in intervention group were higher than those in control group with statistical differences. Conclusions "1+N" extended nursing can improve metabolic indicators, medication compliance and self-management ability among type 2 diabetes patients.

At present,many studies suggest that diabetes patients with Helicobacter pylori infection rate are rate higher than normal crowd,and Hp infection is one of the important pathogenesis of diabetes.But whether Helicobacter pylori in-fection has a correlation with type 2 diabetes mellitus(T2DM)are still controversial,this article will from the Hp infection rate in patients with T2DM and by epidemiological and putative mechanisms discusses the relationship between Hp infection and T2DM and for future related research is discussed.

Objective To summarize the clinical efficacy of Endu combined with intrapleural injection of cisplatin in the treatment of malignant pleural effusion of non-small cell lung cancer.Methods80 patients with malignant pleural effusion were selected from January 2014 to December 2015.The patients were randomly divided into observation group and control group (n=40).The control group was given Endu(40mg/time, 1 time/week) combined with cisplatin (40mg/time, 1 time/week) intraperitoneal injection treatment, the treatment group was given Endu intraperitoneal injection therapy, After 4 weeks of treatment, the clinical efficacy and adverse reactions were observed.ResultsThe clinical efficacy of the observation group was significantly higher than that of the control group (50.00%).The difference was statistically significant (P<0.05).The incidence of adverse reactions in the observation group was 15.00% higher than that in the control group, but the difference was not significant.The improvement rate of life quality in the observation group was significantly higher than that in the control group (52.50%).The difference between the two groups was statistically significant (P<0.05).ConclusionThe clinical efficacy of Endu combined with intrapleural injection of cisplatin in the treatment of malignant pleural effusion of non-small cell lung cancer is superior to that of simple analgesia, which can significantly improve the clinical symptoms and quality of life.It is worthy to be popularized in clinical practice.

Objective To compare the clinical effect of Doxofylline and aminophylline in the treatment of bronchial asthma.Methods The clinical data of 112 patients with bronchial asthma treated in Jiaxing Second Hospital from February 2015 to December 2016 were retrospectively analyzed.The patients were divided into two groups: the treatment group(56 cases), the use of doxofylline treatment, and the control group(56 cases), the use of aminophylline treatment.After 1 w treatment, the curative effect and adverse reactions were compared between the two groups to observe the changes of lung function before and after treatment.Results The total effective rate of the treatment group and the control group were 91.07% and 76.79% respectively(P<0.05).After treatment, the FVC of the treatment group was(2.24±0.63)L, FEV1 was(1.59±0.47)L, VC was(2.94±0.77)L, the incidence of adverse reactions was 10.71%, which was superior to the control group, the difference was statistically significant(P<0.05).Conclusion Doxofylline treatment of bronchial asthma clinical efficacy is remarkable, worthy of clinical promotion.

OBJECTIVETo test the efficiency of transfecting (99)Tc(m)-labeled anti-miR208b oligonucleotide into early hypertrophic cardiac myocytes in vitro.

METHODSThe anti-oligonucleotide targeting miR208b (AMO) was synthesized and modified with LNA followed by conjugation with N-hydroxysuccinimidyl S-acetyl-meraptoacetyl triglycine (NHS-MAG3) and radiolabeling with (99)Tc(m). NHS-MAG3-LNA-AMO and labeled AMO were purified with Sep-Pak C18 column chromatography, and the former was examined for UV absorption at the 260 nm using Gene Quant DNA/RNA calculator. The labeling efficiency, radiochemical purity, stability and molecular hybridization activity were analyzed. An angiotensin II-induced cell model of hypertrophic cardiac myocytes was transfected with (99)Tc(m)-NHS-MAG3-LNA-AMO via liposome, and the relative expression of miRNA208b and retention ratio of the labeled AMO in early hypertrophic cells were determined.

RESULTSThe labeling efficiency and radiochemical purity of the labeled AMO after purification exceeded 84% and 86%, respectively. The radio- chemical purities of the labeled AMO incubated in serum and normal saline for 12 h were both higher than 80%, and the labeled AMO showed a capacity to hybridize with the target gene. In the hypertrophic model of cardiac myocytes, the retention ratio of labeled AMO at 6 h was higher than 20%.

CONCLUSIONThe (99)Tc(m)-labeled antisense probe can be efficiently transfected into hypertrophic cardiac myocytes in vitro, which provides an experimental basis for subsequent radionuclide imaging studies.

Humans ; Isotope Labeling ; Liposomes ; MicroRNAs ; genetics ; Myocytes, Cardiac ; Oligonucleotides ; Oligonucleotides, Antisense ; Oligopeptides ; Radiopharmaceuticals ; Silicon Dioxide ; Succinimides ; Transfection

Objective To test the efficiency of transfecting 9 Tcm-labeled anti-miR208b oligonucleotide into early hypertrophic cardiac myocytes in vitro. Methods The anti-oligonucleotide targeting miR208b (AMO) was synthesized and modified with LNA followed by conjugation with N-hydroxysuccinimidyl S-acetyl-meraptoacetyl triglycine (NHS-MAG3) and radiolabeling with 9 Tcm. NHS-MAG3-LNA-AMO and labeled AMO were purified with Sep-Pak C18 column chromatography, and the former was examined for UV absorption at the 260 nm using Gene Quant DNA/RNA calculator. The labeling efficiency, radiochemical purity, stability and molecular hybridization activity were analyzed. An angiotensin II-induced cell model of hypertrophic cardiac myocytes was transfected with 9 Tcm-NHS-MAG3-LNA-AMO via liposome, and the relative expression of miRNA208b and retention ratio of the labeled AMO in early hypertrophic cells were determined. Results The labeling efficiency and radiochemical purity of the labeled AMO after purification exceeded 84% and 86%, respectively. The radio-chemical purities of the labeled AMO incubated in serum and normal saline for 12 h were both higher than 80%, and the labeled AMO showed a capacity to hybridize with the target gene. In the hypertrophic model of cardiac myocytes, the retention ratio of labeled AMO at 6 h was higher than 20%. Conclusion The 9 Tcm-labeled antisense probe can be efficiently transfected into hypertrophic cardiac myocytes in vitro, which provides an experimental basis for subsequent radionuclide imaging studies.

Objective To test the efficiency of transfecting 9 Tcm-labeled anti-miR208b oligonucleotide into early hypertrophic cardiac myocytes in vitro. Methods The anti-oligonucleotide targeting miR208b (AMO) was synthesized and modified with LNA followed by conjugation with N-hydroxysuccinimidyl S-acetyl-meraptoacetyl triglycine (NHS-MAG3) and radiolabeling with 9 Tcm. NHS-MAG3-LNA-AMO and labeled AMO were purified with Sep-Pak C18 column chromatography, and the former was examined for UV absorption at the 260 nm using Gene Quant DNA/RNA calculator. The labeling efficiency, radiochemical purity, stability and molecular hybridization activity were analyzed. An angiotensin II-induced cell model of hypertrophic cardiac myocytes was transfected with 9 Tcm-NHS-MAG3-LNA-AMO via liposome, and the relative expression of miRNA208b and retention ratio of the labeled AMO in early hypertrophic cells were determined. Results The labeling efficiency and radiochemical purity of the labeled AMO after purification exceeded 84% and 86%, respectively. The radio-chemical purities of the labeled AMO incubated in serum and normal saline for 12 h were both higher than 80%, and the labeled AMO showed a capacity to hybridize with the target gene. In the hypertrophic model of cardiac myocytes, the retention ratio of labeled AMO at 6 h was higher than 20%. Conclusion The 9 Tcm-labeled antisense probe can be efficiently transfected into hypertrophic cardiac myocytes in vitro, which provides an experimental basis for subsequent radionuclide imaging studies.