OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

ObjectiveTo investigate the effects of EZH1/2 inhibitor UNC1999 on the immune cell phenotypes in peripheral blood of healthy adults. MethodsCCK8 assay was used to measure the cell viability of peripheral blood mononuclear cells （PBMC）. Multicolor flow cytometry was performed to analyze the immunophenotypes. ResultsCompared with DMSO group， UNC1999 group showed increased classical monocytes （CD14⁺⁺CD16^-） ［（19.53±1.79）% vs. （66.60±5.02）%， t=13.31， P=0.006）， decreased intermediate monocytes （CD14⁺⁺CD16⁺） and non-classical monocytes （CD14⁺CD16⁺） ［（35.08±3.97）% vs. （15.42±2.89）%， t=6.130， P=0.026； （35.50±3.53）% vs. （8.40±3.12）%， t=25.740， P=0.002］. The proportions of CD56^dim CD16⁺， CD56^dom CD16⁺ in UNC1999 group were lower ［（3.39±0.86）% vs. （0.27±0.06）%， t=4.882， P=0.040； （80.50±0.64）% vs. （0.63±0.23）%， t=133.100， P<0.000 1］. UNC1999 group exhibited higher frequency of naive B cells ［（10.67±1.76）% vs. （37.99±3.76）%， t=17.690， P=0.003］， lower frequency of memory B cells， transitional B cells， plasmablasts B cells ［（23.39±4.20）% vs. （11.82±1.90）%， t=7.059， P=0.020； （3.58±0.47）% vs. （1.52±0.56）%， t=26.970， P=0.001； （0.18±0.03）% vs. （0.00±0.00）%， t=8.647， P=0.013］. The percentage of DC and mDC/DC was significantly elevated in UNC1999 group ［（0.20±0.05）%vs.（1.38±0.13）%， t=16.500， P=0.004； （32.41±13.14）% vs. （60.87±8.43）%， t=8.252， P=0.014］， with a significantly decreased percentage of pDC/DC ［（24.90±1.95）% vs. （12.70±2.11）%， t=7.566， P=0.017］. Higher proportions of CD8⁺ central memory T cells （TCM） and CD8⁺PD-1⁺ ［（5.62±1.24）% vs. （18.38±2.34）%， t=15.600， P=0.004； （2.50±1.02）% vs. （18.34±2.69）%， t=8.822， P=0.013］， but lower proportions of CD8⁺ effective memory T cells （TEM） and CD4⁺CD27⁺were observed in UNC1999 ［（28.27±10.15）% vs. （15.62±9.48）%， t=19.480， P=0.003； （82.77±2.66）% vs. （56.00±9.01）%， t=5.715， P=0.029］. No statistical difference was found in other cell subsets （P>0.05）. ConclusionUNC1999 can lead to changes in PBMC immunophenotypes.

Objective To investigate the effects of protein intake in the early phase and later phase on the outcomes of critically ill patients.Methods A total of 326 critically ill patients admitted in intensive care unit of our hospital from September 2016 to March 2018 were enrolled in this prospective observational study.According to the 28-day prognosis of patients,they were divided into death group and survival group.Early protein target (EPT) was defined as the daily protein intake≥0.8 g/ (kg · d) on days 1-3,and late protein target (LPT) was defined as the daily protein intake≥0.8 g/ (k · d) on days 4-7.Results Daily protein intakes on day 1 and day 3 and cumulative protein intakes on days 1-3 were significantly higher in non-survivors than in the survivors (P＜0.05),but daily protein intakes on day 2,4,5,6 and 7 and cumulative protein intakes on days 4-7 and 1-7 showed no significant difference between two groups (P＞0.05).Hospital mortality was the lowest in the LPT group,the highest in the EPT,and in the middle in the EPT+LPT group and non-EPT+non-LPT group (P＜0.05).The survival curve analysis showed that the survival time of the EPT-only group was significantly lower than that of the LPT-only group (P＜0.05).Multivariate analysis showed that age,sex,cumulative protein and caloric intakes on days 1-7 were the independent risk factors for mortality.Conclusion Early low protein intake is benefit for the outcomes of critically ill patients,and combined with adequate intake of protein in the later stage may further improve the outcomes.

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Objective To investigate the clinical efficacy of kinetic rectification acupuncture in treating acute facial neuritis. Method Sixty patients with acute facial neuritis were randomized to observation and control groups. The observation group received kinetic rectification acupuncture and the control group, conventional acupuncture alone. Acupuncture was given five times a week, five times as one course. The therapeutic effects were evaluated after three courses of treatment. Result The total efficacy rate was 93.3% in the observation group and 73.3% in the control group; there was a statistically significant difference between the two groups (P<0.05). The latencies and amplitudes of the frontal muscle, orbicularis oculi muscle and quadrate muscle of upper lip improved in the two groups after treatment and had statistically significant pre-/post-treatment differences (P < 0.01). There were statistically significant differences in the pre-/post-treatment difference values of the latencies and amplitudes of the frontal muscle and orbicularis oculi muscle (P<0.01) and no statistically significant difference in the pre-/post-treatment difference values of the latency and amplitude of the quadrate muscle of upper lip (P>0.05) between the two groups. Conclusion Kinetic rectification acupuncture has a marked therapeutic effect on acute facial neuritis. This study provides a particular therapeutic method for clinical practice.

ObjectiveTo investigate the effects of Qiangjing Tablets (QJT) on sperm quality and the MAPK signaling pathway in the SD rat model of asthenospermia (AS).

METHODSA total of 100 male SD rats were randomly divided into five groups of equal number, blank control, AS model control, high-dose QJT, medium-dose QJT, and low-dose QJT. All the rats were intragastrically administered ORN at 200 mg/kg/d for establishment of the AS model except those in the blank control group, which were given 1% CMC sodium solution at 1 ml/100 g by gavage. Meanwhile the animals of the high-, medium-, and low-dose QJT groups were gavaged with QJT at 6700, 3300 and 1700 mg/kg/d, respectively, qd 6 days a week for 20 days. Then the testis issue and the apoptosis of the testicular cells were observed under the electron microscope, the expression of vimentin in the testis was determined with the immunohistochemical SP method, that of ERK1/2 detected by Western blot, and the concentration of TGF-β1 in the semen measured by ELISA.

RESULTSThe AS model controls showed round nuclei of spermatocytes, homogeneously distributed chromatins, broken or lost mitochondria, and expanded rough endoplasmic reticulum in the testis tissue. In comparison, the rats of the high-, medium-, and low-dose QJT groups exhibited round nuclei of spermatocytes, homogeneously distributed chromatins, and well-structured mitochondria, rough endoplasmic reticulum and ribosome, which were all similar those of the blank controls. Compared with the blank controls, the AS model rats manifested significantly increased expressions of ERK1/2 (1.00 ± 0.00 vs 1.26 ± 0.10, P<0.01) and vimentin (0.16 ± 0.01 vs 0.17 ± 0.01, P<0.01) and apoptosis rate of cells in the testis tissue (［9.20 ± 3.07］ vs ［42.20 ± 9.17］ %, P<0.01), but decreased level of TGF-β1 in the semen (［627.67 ± 26.07］ vs ［566.73 ± 68.44］ ng/ml, P<0.05). In comparison with the model controls, the rats of the high- and medium- -dose QJT groups presented remarkably down-regulated expressions of ERK1/2 (1.26 ± 0.10 vs 1.14 ± 0.08, P<0.01; 1.26 ± 0.10 vs 1.18 ± 0.05, P<0.05) and vimentin (0.17 ± 0.01 vs 0.16 ± 0.01, P<0.01; 0.17 ± 0.01 vs 0.17 ± 0.09, P<0.05) and decreased rate of cell apoptosis (［42.20 ± 9.17］ vs ［21.60 ± 5.94］ %, P<0.01; ［42.20 ± 9.17］ vs ［33.95 ± 6.39］ %, P<0.05). The concentration of TGF-β1 in the semen was markedly lower in the high-dose QJT than in the AS model control group (［621.78 ± 30.80］ vs ［566.73 ± 68.44］ ng/ml, P < 0.05).

CONCLUSIONSQiangjing Tablets could improve semen quality in asthenospermia rats by acting against oxidative stress.

Animals ; Apoptosis ; Asthenozoospermia ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Mitogen-Activated Protein Kinases ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Semen ; Semen Analysis ; Signal Transduction ; Spermatozoa ; Testis ; metabolism ; ultrastructure ; Transforming Growth Factor beta1 ; metabolism ; Vimentin ; metabolism

OBJECTIVETo detect the expression of MCL-1 in patient with acute myeloid leukemia(AML) with normal karyotype and to investigate the relationship of its expression level with clinical parameters and prognosis.

METHODSThe expression of MCL-1 in the bone marrow from 37 newly diagnosed AML patients was measured by real-time fluorescent quantitative PCR(FQ RT-PCR) and Western blot, and the relationship between its expression level and clinical parameters such as the age, sex, WBC count, Hb level, Plt count, blast ratio in BM, and sensitivity to chemotherapeutic drugs in vitro prognosis was analyzed.

RESULTSThe expression level of MCL-1 did not correlate with the age, sex, WBC count, Hb level, Plt count and the percentage of blast cells. There was no significant difference of MCL-1 expression in AML patients with or without extramedullary infiltration. The higher level of MCL-1 existed in AML patients who did not achieve complete remission with classical regimen. The resistant rate to chemotherapeutic drugs in vitro was higher in the patients with higher level of MCL-1.

CONCLUSIONOverexpression of MCL-1 is closely related with the resistance to chemotherapeutic drugs, and may be used as an early indicator for judging multi-drug resistance and prognosis of AML.

The study aims at predicting ecological suitability of Ephedra intermedia in China by using maximum entropy Maxent model combined with GIS, and finding the main ecological factors affecting the distribution of E. intermedia suitability in appropriate growth area. Thirty-eight collected samples of E. intermedia and E. intermedia and 116 distribution information from CVH information using ArcGIS technology were analyzed. MaxEnt model was applied to forecast the E. intermedia in our country's ecology. E. intermedia MaxEnt ROC curve model training data and testing data sets the AUC value was 0.986 and 0.958, respectively, which were greater than 0.9, tending to be 1.The calculated E. intermedia habitat suitability by the model showed a high accuracy and credibility, which indicated that MaxEnt model could well predict the potential distribution area of E. intermedia in China.

OBJECTIVETo investigate the effects and mechanisms of the combination of homoharringtonine (HHT) with arsenic trioxide(AsO) on human myeloid cell line U937 in vitro.

METHODSMTT method was used to determine the antiproliferating effect of different concentrations of HHT, AsOand their combination on U937 cells; the flow cytometry with Annexin-V-FITC/PI double staining was used to determine the apoptosis-induced effect of HHT and AsOalone or their combination; Western blot method was used to detect the protein expression of P-Akt,P-Akt,BCL-XL, BID,MCL-1,P-MCL-1 and so on.

RESULTSHHT and AsOcould significantly inhibit proliferation of U937 cells and induce their apoptosis. The combination of these 2 drugs could significantly enhance the early apoptosis of U937 cells. After combination of these 2 drugs was used, the protein expressions of P-Akt,P-Akt,MCL-1,P-MCL-1 and BCL-XL were obviously down-regulated, but the expression of BID protein did not change.

CONCLUSIONThe combination treatment of HHT and AsOcan synergistically inhibit the growth of U937 cells through inhibition of PI3K/Akt signal way and MCL-1 protein.