BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

Objective To study the effect of Shenqi Fuzheng injection on proliferation of gastric cancer cell line SGC7901, and to explore its mechanism associated with the STAT3 pathway. Methods The human gastric cancer cell line SGC7901 was used as the research object, the effects of different concentrations of Shenqi Fuzheng injection on the activity of SGC7901 cells were observed by MTT method, the levels of interleukin(IL)-6,IL-8 and IL-11 were detected by enzyme-linked immunosorbent assay(ELISA), and the expressions of Janus kinase 2(JAK2), STAT3 and phosphorylated-STAT3(p-STAT3) were detected by Western blot. Results Compared with the control group,the activity of SGC7901 cells in the treatment group decreased significantly, and the concentration of Shenqi Fuzheng injection reached 0.1 mg/ml, the inhibitory rate of SGC7901 cells reached (10.8±0.7) %, and the difference was statistically significant (P< 0.01). With the increase of Shenqi Fuzheng injection concentration, the inhibition rate of SGC7901 cells increased gradually (F =12.319, P =0.000). Compared with the control group, with the increase of Shenqi Fuzheng injection concentration, IL-6, IL-8 and IL-11 contents were decreased in SGC7901 cells, the differences were statistically significant (IL-6: F = 31.256, P = 0.000; IL-8: F = 16.857, P = 0.000; IL-11: F = 21.319, P =0.000);JAK2 and p-STAT3 protein levels were significantly reduced(JAK2:F =12.315,P =0.000;p-STAT3:F= 16.728, P= 0.000) in the treatment groups. Conclusion Shenqi Fuzheng injection can inhibit the proliferation of SGC7901 cells,and the mechanism may be related to the inhibition of STAT3 pathway.

Objective To investigate the guidance of the endoscopic ultrasonography for the surgery selec-tion of patients with low rectal cancerthrough analyzing the accuracy of endoscopic ultrasonography in preoperative TN staging. Methods Eighty-seven cases with low rectal cancer received preoperative endoscopic ultrasonography examination,the preoperative staging and the postoperative pathologic comparison. The EUS accuracy of preopera-tive staging of rectal cancer was evaluated. Results The preoperative staging with endoscopic ultrasonography for patients with low rectal cancer,100% in T1 stage,96.0% in T2 stage,85.7% inT3 stage,and 100% in T4 stage. The preoperative staging and the postoperative pathologic comparison in T stage were consistent(Kappa = 0.903, P < 0.05). The preoperative staging with endoscopic ultrasonography for patients with low rectal cancer ,87.0% in N0 stage,78.6% in N1 stage,and 100% in N2. The preoperative and the postoperative pathologic comparisons in N stage were consistent(Kappa = 0.768,P < 0.05). Conclusion The endoscopic ultrasonography had a certain advantage in the clinical preoperative evaluation for patients with low rectal cancer ,especially for invasion depth and the judgment of lymph node metastasis ,with a higher accuracy.

Objective To compare the therapeutic effects between cervical and extra-cervical surgical approaches for endoscopic thyroidectomy . Methods From October 2012 to December 2013, forty-four thyroid goiter patients were divided into two groups randomly .Group A underwent modified Miccoli endoscopic thyroidectomy ( n =20 ) and group B underwent endoscopic thyroidectomy via breast areola approach ( n=24 ) .The operative time , intraoperative blood loss , pain in 24 hours postoperatively , drainage volume , postoperative hospital stay , hospital cost , complication and cosmetic results between the two groups were compared . Results Compared with group B, group A had shorter operative time [(77.9 ±28.3) min vs.(97.9 ±30.0) min, t=-2.259, P=0.029], less intraoperative blood loss [(15.9 ±8.7) ml vs.(29.5 ±16.1) ml, t=-3.384, P=0.002], less pain in 24 hours postoperatively ( no pain, endurable pain , intolerable pain in group A and B were 15, 5, 0 and 7, 15, 2 cases respectively , Z=-3.066, P=0.002), less postoperative drainage volume [(31.7 ±10.3) ml vs.(57.0 ±14.6) ml, t=-6.511, P=0.000], but poorer cosmetic results (very dissatisfied, not satisfied, satisfied, comparatively satisfied, and very satisfied in group A and B were 1, 4, 5, 6, 4 and 0, 1, 4, 5, 14 cases respectively, Z=-2.723, P=0.006).There was no significant difference in postoperative hospital stay and hospital cost between the two groups (P>0.05).One case suffered transient hoarseness in group A and one case had trembling hand due to low calcium level in group B and both of them recovered 1 month after symptomatic treatment .No permanent recurrent laryngeal nerve injury , parathyroid injury or other complications occurred in both groups . Conclusions Cervical approach is minimally invasive and leads to good cosmetic results while extra-cervical approach causes bigger trauma but leads to better cosmetic results.Patients with high cosmetic reguest may choose endoscopic thyroidectomy via breast areola approach .

Objective To estimate the curative effect of non-gastrointestinal decompression in laproscopic colorectal surgery. Methods By using the single-blind-random test and prospective study, 55 patients were divided into two groups, experimental group and matched group. The difference of operating time, gastrointestinal function recovery time, adverse effect, complication, average length of hospital stay between two groups were observed and evaluated. Results The difference of operating time, gastrointestinal function recovery time, adverse effect, complication, average length of hospital stay between two groups were not statistically significant(P>0.05). The incidence rate of sore throat and cough and expectoration difficulty after operation was significantly lower in the experimental group (the rate was respectively 16.0% vs 77.7% and 8.0% vs 50.0, P<0.05). However, The incidence rate of nausea and vomiting, abdom-inal distension was not statistically significant(P>0.05). Conclusion In the perioperative period of laproscopic colorectal surgery, non-gastrointestinal decompression appears to be security and feasible.

OBJECTIVETo investigate the role of protein kinase C (PKC) in thrombin-induced monocyte chemoattractant protein-1(MCP-1) release by human lung fibroblasts (HLF-1).

METHODSCultured human lung fibroblasts HLF-1 were incubated with different concentrations of PKC inhibitors before by thrombin stimulation. MCP-l protein levels in the supernatants were assessed using ELISA, and MCP-1 mRNA levels in the cell lysate were measured by quantitative real-time PCR.

RESULTSThe broad spectrum PKC inhibitors bisindolylmaleimide I and RO-31-8220 obviously inhibited thrombin-induced MCP-l mRNA and protein expressions in HLF-1 cells, whereas Ca(2+)-dependent PKC inhibitor Go 6976 had no such effects.

CONCLUSIONCa(2+)-independent PKC mediates thrombin-induced MCP-1 release in cultured HLF-1 cells.

Cell Line ; Cells, Cultured ; Chemokine CCL2 ; metabolism ; Fibroblasts ; metabolism ; Humans ; Indoles ; pharmacology ; Lung ; cytology ; metabolism ; Protein Kinase C ; antagonists & inhibitors ; Thrombin ; pharmacology

Objective To develop a new single-tube polymerase chain reaction amplification (ST Amp) protocol for the efficient sequencing-based typing (SBT) of human leukocyte antigen DRB1(HLA-DRB1).Methods A set of 7 group-specific exonic 5′ amplification primers and a single generic 3′ primer were included together in a single PCR mix to facilitate a single PCR amplification per sample for HLA-DRB1 typing.Results All samples were successfully typed, the typing result was accurate and repeatable.Conclusion ST Amp technique has resulted in the ability to perform high-resolution, high-specificity and high-throughput HLA-DRB1 typing by DNA sequencing.