Objective To explore the relationship between systemic immune-inflammation index(SII)and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)complicat-ed with type Ⅱ respiratory failure.Methods A total of 92 patients with AECOPD complicated with type Ⅱrespiratory failure admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University from February 2022 to February 2024 were selected as the research subjects.According to the 28-day survival status,they were di-vided into the survival group(n=69)and the death group(n=23).The counts of neutrophils,lymphocytes and platelets of the patients were detected by the fully automatic hematology analyzer,and SII was calculated.The receiver operating characteristic curve was used to analyze the predictive value of SII for the prognosis of patients.Multivariate Logistic regression analysis was used to explore the influencing factors of prognosis in patients.Results The platelet count,neutrophil count,SII and acute physiology and chronic health evaluationⅡ(APACHE Ⅱ)score in the survival group were lower than those in the death group,while the lymphocyte count in the survival group was higher than that in the death group,the differences were statistically signifi-cant(P＜0.05).In patients with AECOPD complicated with type Ⅱ respiratory failure,SII was positively correlated with APACHEⅡ score(r=0.612,P＜0.001).The areas under the curve(AUC)of platelets,neu-trophils and lymphocytes in predicting the prognosis of patients with AECOPD complicated with type Ⅱ re-spiratory failure were 0.776(95％CI:0.731-0.826),0.849(95％CI:0.799-0.894),and 0.732(95％CI:0.687-0.782),respectively,the AUC of SII in predicting the prognosis of patients with AECOPD complicat-ed with type Ⅱ respiratory failure was 0.925(95％CI:0.880-0.975).The proportion of death groups com-bined with heart diseases and blood urea nitrogen(BUN),B-type natriuretic peptide(BNP)were higher than those in the survival group,while hemoglobin(Hb)was lower than that in the survival group,and the differ-ences were statistically significant(P＜0.05).Combined cardiac diseases,BUN,Hb,BNP and SII were the in-fluencing factors for the prognosis of patients with AECOPD complicated with type Ⅱ respiratory failure(P＜0.05).Conclusion The increase of SII is related to the prognosis of patients with AECOPD complicated with type Ⅱ respiratory failure,and it has certain predictive value for the prognosis of patients with AECOPD complicated with type Ⅱ respiratory failure.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells to hypoxia. Bruceine D (BD) is an isolated natural quassinoid with multiple anti-cancer effects. Here, we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism. Using biophysical proteomics approaches, we identified inhibitor of β-catenin and T-cell factor (ICAT) as the functional target of BD. By targeting ICAT, BD disrupted the interaction of β-catenin and ICAT, and promoted β-catenin degradation, which in turn induced the decrease of HIF-1α expression. Furthermore, BD could inhibit HCC cells proliferation and tumor growth in vivo, and knockdown of ICAT substantially increased resistance to BD treatment in vitro. Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.

Objective To evaluate the efficacy of endoscopic ultrasound guided biliary drainage (EUS-BD) in patients with biliary obstruction and surgically altered anatomies.Methods We collected data from 33 patients with biliary obstruction and surgically altered anatomies from January 2016 to January 2018 in Zhejiang University School of Medicine Affiliated Hangzhou First People's Hospital who underwent EUS-guided biliary drainage after unsuccessful ERCP.The operation success rate,clinical success rate,complication rate,hospital stay were studied.Results Of 33 patients,31 were successfully operated and stented using endoscopic ultrasound puncture:14 patients through the stomach,17 patients through the duodenum;8 patients by the rendezvous approach.The operation success rate was 93.9％.Of the 33 patients,28 had a significant decrease in jaundice,with a clinical success rate of 84.9％.Complications consisted of 2 patients with bleeding and 1 patient with cholangitis.These patients improved after conservative treatment.The complications rate was 9.1％.The hospital stay was (12.4±5.7) d.Conclusion EUS-BD can be the first choice for patients with biliary obstruction and surgically altered anatomy after failed endoscopic retrograde cholangiograohv in centers with exoertise in EUS-BD procedures.

Objective To study the therapeutic effects of EUS-guided biliary drainage (EUS-BD) using a nitinol fully covered self-expandable metal stents in patients with malignant obstructive jaundice after failed ERCP.Methods From January 2016 to January 2018,all patients with malignant obstructive jaundice who failed ERCP underwent EUS-guided biliary drainage using nitinol fully covered self-expandable metal stent at Affiliated Hangzhou First People' s Hospital,Zhejiang University School of Medicine.The operation success rate,liver functional recovery time,complication rate,length of hospital stay and survival time were observed.Results Of 36 patients who underwent EUS-guided biliary drainage,34 were successfully performed,with 19 through the stomach,and 15 through the duodenum.The operation success rate was 94.4％ (34/36).The liver functional recovery time of the 34 patients were 25.8 ±.6.5 days.One patient developed hemobilia and one cholangitis,both improved after conservative treatment.The total complication rate was 5.6％ (2/36).The hospital stay and survival time were 21.5 ± 4.7 days and 220.5 ± 54.8 days,respectively.Conclusion EUS-BD using nitinol fully covered self-expandable metal stents was a feasible and effective treatment in patients with malignant biliary obstruction after failed ERCP.

Based on collections and researches of Pesudostellaria heterophylla germplasm resources from different areas of China, by using Shibing SB-4 provenance as materials, the new variety "Shitai No.1" was bred by mass selection, small plot variety comparative test, regional variety comparative test and field trial planting. Compared with "Qian taizishen No.1" and P. heterophylla land races. The disease and lodging resistance, root yield, polysaccharide content and the first grade rate of "Shitai No.1" have obvious advantages. In addition, it is relatively stable of yield in "Shitai No.1" in different places. It is demonstrated that "Shitai No.1" is a fine variety that adapt to the producing areas of P. heterophylla in Guizhou province, it is worthy to be promoted.

To establish a prokaryotic expression and purification protocol for nuclease P1 (NP1), we first obtained a synthetic NP1 by splicing 22 oligonucleotides with overlapping PCR. We constructed and transformed a secretory expression vector pMAL-p4X-NP1 into Escherichia coli host strains T7 Express and Origami B (DE3) separately. Then, the recombinant NP1 was purified by amylose affinity chromatography, and its activity, thermo-stability and metal-ion dependence were investigated systematically. The results indicated that the expressed fusion proteins MBP-NP1 (Maltose binding protein-NP1) existed mainly in soluble form both in host strains T7 Express and Origami B (DE3), but the specific activity of recombinant protein from Origami B(DE3) strain was higher than T7 Express strain (75.48 U/mg : 51.50 U/mg). When the MBP-tag was cleaved by protease Factor Xa, the specific activity both increased up to 258.1 U/mg and 139.2 U/mg. The thermal inactivation experiments demonstrated that the recombinant NP1 was quite stable, and it retained more than 90% of original activity after incubated for 30 min at 80 degrees C. Zn2+ (2.0 mmol/L) could increase enzyme activity (to 119.1%), on the contrary, the enzyme activity was reduced by 2.0 mmol/L Cu2+ (to 63.12%). This research realized the functional expression of NP1 in the prokaryotic system for the first time, and provided an alternative pathway for NP1 preparation.
Cloning, Molecular ; Enzyme Stability ; Escherichia coli ; genetics ; metabolism ; Fungal Proteins ; biosynthesis ; genetics ; metabolism ; Genes, Synthetic ; Genetic Vectors ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; metabolism ; Single-Strand Specific DNA and RNA Endonucleases ; biosynthesis ; genetics ; metabolism

Wheat grain peroxidase 1 (WP1) belonged to class III plant peroxidase with cofactor heme, which not only has antifungal activity, but also influences the processing quality of flour. In order to enhance functional expression of WP1 in prokaryotic system by increasing endogenous heme synthesis, we constructed a recombinant plasmid pACYC-A-L containing hemA and hemL of Esherichia coli. Then, we co-transformed it into host strain T7 Express with secretive expression vector (pMAL-p4x-WP1) or non-secretive expression vector (pET21a-MBP-WP1), respectively. The MBP-WP1 fusion protein was further purified by amylose affinity chromatography and its peroxidase activity was assayed using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) as substrate. At 12 h after induction at 28 degree, the extracellular 5-aminolevulinic acid (5-ALA) production of T7 Express/pACYC-A-L was up to 146.73 mg/L, simultaneously the extracellular porphrins also increased dramatically. The peroxidase activity of functional MBP-WP1 obtained from T7 Express/ (pACYC-A-L + pMAL-p4x-WP1) was 14.6-folds of that purified from T7 Express/ pET21a-MBP-WP1. This study not only successfully enhanced functional expression of wheat peroxidase 1 in Esherichia coli, but also provided beneficial references for other important proteins with cofactor heme.
Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; genetics ; Heme ; biosynthesis ; genetics ; Peroxidases ; biosynthesis ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Transformation, Genetic

Objective To examine the effects of the MEK inhibitor on human pancreatic cancer cells, and to explore the molecular mechanisms. Methods Human pancreatic cancer cell lines CFPANC1, PANC1 and MiaPaCa2 were treated with MEK inhibitor PD98059 or DMSO, the sensitivity was analyzed by an MTT assay, and cell cycle distribution was evaluated by flow cytometry( FCM), The transcriptional level and protein expression of tumor suppressor genes were detected by real-time RT-PCR and western blot respectively. DNA methyltransferase (Dnmt)1, 3a and 3b were also assayed by western blot, The methylation status of the promoter of the p16INK4A gene was assayed by methylation-specific PCR (MSP). Results PD98059 inhibited to various degrees the growth of three pancreatic cancer cell lines, accompanied by G0-G1 cell cycle arrest. PD98059 up-regulated the expression of p16INK4a, p21WAF1, p27KIP1 mRNA, demethylated the hypermethylation status of p16INK4a gene promoter, and decreased Dnmtl and Dnmt3b in CFPANC1 and PANC1 cell lines. PD98059 only increased the expression of p27KIP1, while the changes of p16INK4a, p21WAF1 and Dnmt were less marked in MiaPaCa2 cell line. Conclusions MEK inhibitor PD98059 down-regulate the activation of Dnmt and up-regulate tumor supress genes, along with the inhibition of cell proliferation and cell cycle progression.

Objective To explore for the methede and effect of endoscopic treatment on biliary leakage and biliary duct damage. Methods All patients with biliary damage such as biliary leakage and biliary duct stricture were treated by endoscopic sphincoterotomy and endoscopic nasobiliary drainage (ENBD) during abdominal cavity drainage ENBD was removd when biliary leakage healed and abdominal cavity drainage ceased for 1～2 weeks were confirmed. Plastic stents were implanted to distend the biliary duct stricture for 2-3 months. Results Twenty-six patients with biliary leakage were cured 3-4 weeks after ENBD. Fourteen out of 17 patients implanted with plastic stent were recovered uneventfully after stent removed, and 4 patients also recovered after installation of double-stents for 3 months, while another case with calculus and stricture of left hepatic duct in spite of implantation of simple-stent suffered repeatedly from biliary tract infection and one case developed hepatic abscess after repeatedly infection for one year before he had the hepatic lobectomy. Conclution Endoscopic therapy is the first choice in treating biliary leakage or secondary duct stricture.