Objective:To investigate the effects and underlying mechanisms of the hypoxia-inducible factor-1α (HIF-1α) agonist Roxadustat in alleviating pulmonary ischemia-reperfusion injury (IRI) in mice.Method:This study consisted of both in vivo and in vitro experiments. Thirty-six male C57/BL6 mice (6~8 weeks old) were used. In the animal experiments, 20 mice underwent left pulmonary artery ligation to establish the IRI model and were divided into reperfusion groups of 0, 1, 2, or 4 hours (IR-0/1/2/4 h, n=4 each), with a sham group ( n=4) as control. Temporal and spatial changes in pulmonary HIF-1α expression were analyzed. Another 16 mice were randomized into four groups: sham ( n=4), I/R+vehicle (DMSO, n=4), and I/R+Roxadustat treatment at 25 mg/kg or 50 mg/kg (I/R+ROX-LD, I/R+ROX-HD, n=4 each). Roxadustat or DMSO was administered intraperitoneally once daily for 5 days before surgery. Lung injury, inflammation, and endothelial apoptosis were subsequently assessed. In the cell experiments, human umbilical vein endothelial cell (HUVEC) was subjected to hypoxia-reoxygenation (H/R) to determine the time course of HIF-1α expression. Cells pretreated with Roxadustat (25 μmol) were then exposed to H/R, and HIF-1α expression and apoptosis were analyzed. To verify the role of HIF-1α, siRNA knockdown of HIF-1α mRNA was performed before Roxadustat pretreatment and H/R exposure. Result:In vivo, pulmonary HIF-1α mRNA expression increased progressively after reperfusion, while protein expression peaked early and subsequently declined ( P<0.05). Immunofluorescence staining revealed HIF-1α predominantly localized to pulmonary endothelial cells following I/R. Compared with the I/R+DMSO group, Roxadustat (both doses) upregulated HIF-1α expression in lung tissue. In vitro, HIF-1α mRNA expression increased continuously after H/R, while protein levels first rose and then decreased ( P<0.05). Roxadustat pretreatment upregulated Bcl-2 and downregulated Bax and cleaved caspase-3 compared with the H/R group ( P<0.05). HIF-1α knockdown reversed these effects, resulting in decreased Bcl-2 and increased Bax and cleaved caspase-3 expression relative to the Roxadustat-treated group. Conclusion:The HIF-1α agonist Roxadustat inhibits vascular endothelial apoptosis, alleviates endothelial injury, reduces inflammatory cell infiltration in lung tissue, and lowers inflammatory responses in mice with pulmonary ischemia-reperfusion injury.

Objective:To investigate the effects and underlying mechanisms of the hypoxia-inducible factor-1α (HIF-1α) agonist Roxadustat in alleviating pulmonary ischemia-reperfusion injury (IRI) in mice.Method:This study consisted of both in vivo and in vitro experiments. Thirty-six male C57/BL6 mice (6~8 weeks old) were used. In the animal experiments, 20 mice underwent left pulmonary artery ligation to establish the IRI model and were divided into reperfusion groups of 0, 1, 2, or 4 hours (IR-0/1/2/4 h, n=4 each), with a sham group ( n=4) as control. Temporal and spatial changes in pulmonary HIF-1α expression were analyzed. Another 16 mice were randomized into four groups: sham ( n=4), I/R+vehicle (DMSO, n=4), and I/R+Roxadustat treatment at 25 mg/kg or 50 mg/kg (I/R+ROX-LD, I/R+ROX-HD, n=4 each). Roxadustat or DMSO was administered intraperitoneally once daily for 5 days before surgery. Lung injury, inflammation, and endothelial apoptosis were subsequently assessed. In the cell experiments, human umbilical vein endothelial cell (HUVEC) was subjected to hypoxia-reoxygenation (H/R) to determine the time course of HIF-1α expression. Cells pretreated with Roxadustat (25 μmol) were then exposed to H/R, and HIF-1α expression and apoptosis were analyzed. To verify the role of HIF-1α, siRNA knockdown of HIF-1α mRNA was performed before Roxadustat pretreatment and H/R exposure. Result:In vivo, pulmonary HIF-1α mRNA expression increased progressively after reperfusion, while protein expression peaked early and subsequently declined ( P<0.05). Immunofluorescence staining revealed HIF-1α predominantly localized to pulmonary endothelial cells following I/R. Compared with the I/R+DMSO group, Roxadustat (both doses) upregulated HIF-1α expression in lung tissue. In vitro, HIF-1α mRNA expression increased continuously after H/R, while protein levels first rose and then decreased ( P<0.05). Roxadustat pretreatment upregulated Bcl-2 and downregulated Bax and cleaved caspase-3 compared with the H/R group ( P<0.05). HIF-1α knockdown reversed these effects, resulting in decreased Bcl-2 and increased Bax and cleaved caspase-3 expression relative to the Roxadustat-treated group. Conclusion:The HIF-1α agonist Roxadustat inhibits vascular endothelial apoptosis, alleviates endothelial injury, reduces inflammatory cell infiltration in lung tissue, and lowers inflammatory responses in mice with pulmonary ischemia-reperfusion injury.

ObjectiveTo discriminate the age of Arisaema Cum Bile， the combination of headspace solid-phase microextraction （HS-SPME） with gas chromatography-mass spectrometry （GC-MS） was applied to explore the differences of volatile components of unfermented， 1-year fermented， 2-year fermented， and 3-year fermented Arisaema Cum Bile. MethodSamples with different fermentation durations were collected and HS-SPME-GC-MS technology was employed to detect the volatile components of each sample. The relative contents of detected volatile components were processed and analyzed by chemometrics methods such as principal component analysis （PCA）， hierarchical cluster analysis （HCA）， and partial least squares discriminant analysis （PLS-DA）. ResultThe results showed that 145 volatile components were identified. Among these volatile components， the relative contents of heterocyclic， alcohols， aldehydes and aromatics were high. PCA， HCA， and PLS-DA can effectively separate Arisaema Cum Bile with four different ages. Based on variable importance in projection （VIP） value > 1， 73 markers of differential volatile components were identified. The content of 2，6，11-trimethyldodecane and m-xylene in unfermented samples was the highest， and the content difference between them and those in fermented samples was significant （P<0.05）. 2，3-butanediol was detected only in 1-year samples， octane was detected only in 2-year samples， and ethyl heptanoate was detected only in 3-year samples. These components can be used as odor markers for Arisaema Cum Bile with different fermentation years. ConclusionThe identification method of volatile components of Arisaema Cum Bile was established by HS-SPME-GC-MS technology， which can realize the rapid identification of unfermented， 1-year fermented， 2-year fermented， and 3-year fermented samples， and provide a scientific basis for the standardization of processing technology and quality standards of Arisaema Cum Bile.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for evaluating blood supply pattern of pancreatic ductal adenocarcinoma(PDAC).Methods A total of 210 single PDAC patients proved by pathology who underwent CEUS and contrast enhanced CT(CECT)examination were retrospectively enrolled.Blood supply patterns of PDAC,i.e.deficient or rich blood supply were evaluated based on findings of CEUS 25 s(CEUS-25 s)and 35 s(CEUS-35 s)after contrast agents injection and CECT,respectively.The evaluation results were compared among different methods.Disease free survival(DFS)and overall survival(OS)of patients with deficient and rich blood supply PDAC shown on CEUS-25 s were followed up and compared.Results CEUS-25 s found 60.00％(126/210)PDAC with deficient blood supply(poor blood supply group),while 40.00％(84/210)with rich blood supply(rich blood supply group).CEUS-35 s showed that the proportion deficient blood supply PDAC increased to 70.48％(148/210,P＜0.05),22 lesions changed from rich blood supply pattern on CEUS-25 s to deficient blood supply pattern.CECT displayed deficient blood supply in 91.90％(193/210)PDAC but rich blood supply in 8.10％(17/210)PDAC,both being significant different compared with results of CEUS-25 s and CEUS-35 s(both P＜0.05).Fifteen-five cases in deficient blood supply group and 39 in rich blood supply group completed 12(8,25)months'follow-up,and the median DFS of patients in deficient blood supply group and rich blood supply group was 8(6,10)and 12(7,17)months,respectively,with the median OS of 14(9,17)and 19(16,24)months,respectively.The median DFS and OS in poor blood supply group were both shorter than those in rich blood supply group(x2=17.227,27.166,both P＜0.001).Conclusion CEUS had important clinical value for evaluating blood supply pattern of PDAC.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for evaluating blood supply pattern of pancreatic ductal adenocarcinoma(PDAC).Methods A total of 210 single PDAC patients proved by pathology who underwent CEUS and contrast enhanced CT(CECT)examination were retrospectively enrolled.Blood supply patterns of PDAC,i.e.deficient or rich blood supply were evaluated based on findings of CEUS 25 s(CEUS-25 s)and 35 s(CEUS-35 s)after contrast agents injection and CECT,respectively.The evaluation results were compared among different methods.Disease free survival(DFS)and overall survival(OS)of patients with deficient and rich blood supply PDAC shown on CEUS-25 s were followed up and compared.Results CEUS-25 s found 60.00％(126/210)PDAC with deficient blood supply(poor blood supply group),while 40.00％(84/210)with rich blood supply(rich blood supply group).CEUS-35 s showed that the proportion deficient blood supply PDAC increased to 70.48％(148/210,P＜0.05),22 lesions changed from rich blood supply pattern on CEUS-25 s to deficient blood supply pattern.CECT displayed deficient blood supply in 91.90％(193/210)PDAC but rich blood supply in 8.10％(17/210)PDAC,both being significant different compared with results of CEUS-25 s and CEUS-35 s(both P＜0.05).Fifteen-five cases in deficient blood supply group and 39 in rich blood supply group completed 12(8,25)months'follow-up,and the median DFS of patients in deficient blood supply group and rich blood supply group was 8(6,10)and 12(7,17)months,respectively,with the median OS of 14(9,17)and 19(16,24)months,respectively.The median DFS and OS in poor blood supply group were both shorter than those in rich blood supply group(x2=17.227,27.166,both P＜0.001).Conclusion CEUS had important clinical value for evaluating blood supply pattern of PDAC.

ObjectiveTo analyze the community structure of endophytes in Panax quinquefolium root and explore the dominant endophytic bacteria and fungi， to provide scientific basis for the establishment of endophytic microbial bank in P. quinquefolium root. MethodInternal Transcribed Spacer （ITS） sequencing and 16S sequencing were performed on six P. quinquefolium root samples collected from Wendeng， Shandong province on PacBio Sequel Ⅱ. ResultA total of 8 phyla， 11 classes， 23 orders， 27 families and 53 genera of endophytic bacteria were identified in P. quinquefolium root， among which an unidentified Burkholderiaceae and an unidentified Rhizobiaceae were dominant. A total of 9 phyla， 23 classes， 35 orders， 43 families and 48 genera of endophytic fungi were identified in P. quinquefolium root， among which an unclassified Helotiales and Pseudogymnoascus were dominant. The community structure of endophytic bacteria revealed that the roots were selectively enriched with nitrogen-fixing bacteria such as unidentified Rhizobiaceae， Bradyrhizobium and Herbaspirillum， which suggested that nitrogen is important for the growth of P. quinquefolium root. The community structure of endophytic fungi indicated that P. quinquefolium in Shandong province might be infected by unclassified Helotiales. ConclusionThere is a rich diversity of endophytic bacteria and fungi in P. quinquefolium root， which provides scientific basis for studying the interaction of the plant with endophytic microorganisms and screening the endophytes to promote the growth of P. quinquefolium root.

Objective To explore the application value of comprehensive nursing path for patients with chronic pelvic inflammatory disease .Methods A total of 180 patients with chronic pelvic inflammation were randomly divided into observation group and control group on average .The control group received routine care for patients with chronic pelvic inflammatory disease , while the observation group underwent comprehensive comprehensive nursing path based on routine .The quality of life , effect of treatment and patients ’ satisfaction were compared .Results After intervention , the dimension assessment score of physical function , physical role , pain, health, vigor, social function, mental health and emotional function were (65.9 ±11.1),(67.8 ± 11.3),(68.1 ±10.0),(77.2 ±12.6),(70.8 ±11.0),(78.0 ±11.5),(77.6 ±11.3) and (80.4 ±10.7) in the observation group, which were better than those in the control group (t =6.983,9.042, 10.819, 19.037, 13.820, 25.174, 17.358, 28.974, respectively;P<0.01).The patients in the observation group had thirty six cured, twenty one dramatically effective, thirty effective and three invalid (Z=5.858,P<0.05). For assessment of satisfaction , there were seventy seven felt very satisfied , eleven satisfied and two unsatisfied (Z =6.678,P <0.05).Conclusions The comprehensive nursing path has a better therapeutic effect for patients with chronic pelvic inflammatory disease by improving the quality of life and treatment satisfaction .

Objective To investigate the clinical significance of quantitatively detecting serum cancer antigen 125(CA125) ,lactate dehydrogenase(LDH) ,β2-microglobulin(β2-MG) and serum ferritin(SF) in primary gastric lymphoma(PGL) .Methods The clini-cal data in 41 cases of PGL confirmed by Pathological examination were retrospectively analyzed on the serum CA 125 ,LDH ,β2-MG and SF levels ,and their relationship with the pathological type ,clinical phase ,grouping ,international prognostic index (IPI) andHe-licobacter pylori infection were compared .Results The serum levels of CA125 ,LDH ,β2-MG and SF in the Ⅲ + Ⅳ stage were high-er than those in the Ⅰ + Ⅱ stage in PGL patients(P<0 .05);the IPI scores in the middle-higher risk + high risk group were obvi-ously higher than those in the lower risk + low-middle risk group (P<0 .01) .There were no significant differences in the patho-logical type ,grouping and Helicobacter pylori infection .Conclusion Detecting the levels of CA125 ,LDH ,β2-MG and SF has the im-portant clinical value to the clinical phase and the prognostic judgment in PGL .