1.Mechanism of gasdermin D on intestinal injury in severe acute pancreatitis by mediating pyroptosis
Tianjiao LIN ; Xinting PAN ; Youdong WAN ; Ziqian WU ; Shaoyan LYU ; Yunyun WANG ; Jingyu SONG ; Fei TIAN
Chinese Critical Care Medicine 2021;33(1):89-94
Objective:To investigate the function of gasdermin D (GSDMD) in intestinal damage of mice with severe acute pancreatitis (SAP).Methods:The healthy C57BL/6 mice were divided into four groups randomly, including normal saline (NS) group, small interfering RNA (siRNA)-NS group, SAP model group and siRNA-SAP group, with 6 mice in each group. The SAP mouse model was reproduced by intraperitoneal injection of caerulein 50 μg/kg combined with lipopolysaccharide (LPS) 10 mg/kg; the NS group was given the same amount of NS; in the siRNA-SAP group and siRNA-NS group, siRNA 50 mg/kg was injected through the tail vein three times before modeling or injection of NS. The blood of mice eyeball in each group was taken 12 hours after modeling, and serum interleukins (IL-1β, IL-18) levels were detected by enzyme linked immunosorbent assay (ELISA). The mice were sacrificed to observe the general changes in abdominal cavity, the pancreas and ileum tissues were taken to observe the pathological changes under a light microscope. The expression of long-chain non-coding RNA uc.173 (lnc uc.173) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect the expression of tight junction proteins zonula occluden-1 (ZO-1) and Occludin in intestinal mucosal epithelial cells. Western blotting was used to detect the GSDMD protein expression level in the intestinal tissue.Results:The serum levels of IL-1β and IL-18 in the SAP model group were significantly higher than those in the NS group and the siRNA-NS group [IL-1β (ng/L): 146.66±1.40 vs. 44.48±5.76, 81.49±10.75, IL-18 (ng/L): 950.47±177.09 vs. 115.43±16.40, 84.84±21.90, all P < 0.05]; and the levels of IL-1β and IL-18 in the siRNA-SAP group were significantly lower than those in the SAP model group [IL-1β (ng/L): 116.26±15.54 vs. 146.66±1.40, IL-18 (ng/L): 689.96±126.08 vs. 950.47±177.09, both P < 0.05]. General observation showed that there were no obvious abnormalities in the abdominal cavity of the mice in the NS and siRNA-NS groups; the mice in the SAP model group and the siRNA-SAP group had different degrees of edema and congestion in the intestine; compared with the SAP model group, the abnormalities in the siRNA-SAP group was significantly reduced. Under light microscope, there were no obvious changes in the pancreas and intestinal mucosa in the NS group and the siRNA-NS group; the pancreatic tissue of the SAP model group and the siRNA-SAP group had different degrees of edema, inflammatory cell infiltration, and lobular structure damage, and the intestinal mucosa was damaged to a certain degree, and the villi were broken to varying degrees, but the damage in the siRNA-SAP group was lighter. The results of RT-PCR showed that the expression of lnc uc.173 in the intestinal tissues of the model SAP group was significantly lower than that of the NS group and the siRNA-NS group (2 -ΔΔCt: 0.26±0.12 vs. 1.01±0.37, 0.67±0.32, both P < 0.05), while the expression of lnc uc.173 in the siRNA-SAP group was significantly higher than that in the SAP model group (2 -ΔΔCt: 0.60±0.39 vs. 0.26±0.12, P < 0.05). Immunohistochemistry showed that ZO-1 and Occludin proteins in the NS group were distributed along the epithelial cells of the intestinal mucosa, showing a strong expression; ZO-1 and Occludin expressions were significantly reduced in the SAP model group and siRNA-SAP group, but the expressions in the siRNA-SAP group was higher than that in the SAP model group. Western blotting showed that the expression level of GSDMD protein in the intestinal tissues of the SAP model group was significantly higher than that of the NS group and the siRNA-NS group [GSDMD protein (GSDMD-N/β-actin): 1.99±0.46 vs. 1, 1.00±0.78, both P < 0.05]. Compared with the SAP model group, the expression of GSDMD protein in the siRNA-SAP group was significantly decreased [GSDMD protein (GSDMD-N/β-actin): 1.42±0.42 vs. 1.99±0.46, P < 0.05]. Conclusions:The systemic inflammatory response and intestinal mucosal barrier damage of SAP mice may be related to the increase of GSDMD expression in intestinal tissues. GSDMD mediates cell pyrolysis to promote the release of inflammatory factors, cause intestinal injury, and down-regulate the expression of intestinal epithelial cell tight junction proteins such as ZO-1 and Occludin, resulting in intestinal mucosal damage.
2.Efficacy of nystatin vaginal effervescent tablets and nifuratel tablet combined with recombinant human interferon alpha 2b suppository in the treatment of candida vaginitis
Chinese Journal of Primary Medicine and Pharmacy 2018;25(4):499-503
Objective To explore the efficacy of nystatin vaginal effervescent tablets , nifuratel tablet combined with recombinant human interferon alpha 2b suppository in the treatment of candida vaginitis .Methods 124 patients with candida vaginitis were selected as the research subjects .The patients were randomly divided into two groups according to different treatment .The control group was treated with nystatin vaginal effervescent tablets +nifuratel tablet,the study group was given recombinant human interferon alpha 2b suppository on the basis of the control group.The symptoms,clinical curative effect,quality of life score,adverse reaction rate were observed and compared in the two groups .Results There were no statistically significant differences between the two groups in symptom and physical signs before treatment (all P>0.05).After treatment,the vulvar itching,burning pain,abnormal leucorrhea,redness symptoms and signs of the study group were (0.95 ±0.44)points,(1.02 ±0.51)points,(1.13 ± 0.62) points,(1.09 ±0.56) points,which were significantly lower than those of the control group [(1.42 ± 0.98)points,(1.28 ±1.02)points,(1.38 ±1.17)points,(1.37 ±1.12)points,t=2.529,2.512,2.505,2.618,all P<0.05].The total effective rate of the study group was 95.2%,which was significantly higher than 74.2% of the control group (Z=-2.839,P<0.05).After treatment,the quality of life scores of physiological function ,bodily pain,mental health,emotional function and social function in the study group were (80.16 ±9.23)points,(84.22 ± 9.95)points,(87.49 ±10.46) points,(89.27 ±12.35) points,(88.21 ±11.74) points,which were significantly higher than those in the control group[(67.58 ±5.34)points,(71.49 ±7.28)points,(73.52 ±7.61)points,(76.83 ±8.32)points,(75.51 ±8.16) points,t=9.728,8.577,9.036,7.039,7.537,all P<0.05].The incidence rate of adverse reactions of the study group was significantly lower than that of the control group (χ2 =10.978,P<0.05). Conclusion Nystatin vaginal effervescent tablets ,nifuratel tablet combined with recombinant human interferon alpha 2b suppository in the treatment of candida vaginitis can significantly improve clinical symptoms ,improve the therapeutic effect,and improve the quality of life of patients with significant clinical value ,it is worthy of reference .
3.Clinical effect of ethinyl estradiol cyproterone tablets combined with ovulation induction in the treatment of polycystic ovary syndrome infertility
Shasha PAN ; Yunyun ZHANG ; Lianju YU
Chinese Journal of Primary Medicine and Pharmacy 2018;25(4):507-511
Objective To explore the clinical effect of ethinyl estradiol cyproterone tablets ( Diane -35 ) combined with ovulation induction in the treatment of polycystic ovary syndrome infertility .Methods 70 patients with polycystic ovary syndrome were enrolled , and they were randomly divided into two groups according to the random number table of the computer ,35 cases in each group .The control group was treated with Diane -35,the observation group was given ovulation induction .The clinical parameters ,vaginal ultrasound results ,cycle ovulation rate ,pregnancy rate,adverse reaction rate and quality of life were compared between the two groups .Results There were no statistically significant differences in uterine volume , intima thickness , bilateral ovarian volume and bilateral follicle number between the two groups after treatment (t=0.055,0.308,0.991,0.435,0.473,0.248,all P>0.05).The cycle ovulation rate of the observation group was significantly higher than that of the control group (80.88% vs. 54.05%,χ2 =8.451,P<0.01).The shape,color,thought and energy score of the observation group were significantly higher than those of the control group (t=4.819,3.519,4.735,6.804,all P<0.01).The pregnancy rate of the observation group was significantly higher than that of the control group (25.71%vs.5.71%,χ2 =5.285,P<0.05). Conclusion Diane-35 combined with ovulation induction in the treatment of polycystic ovary syndrome infertility has significant clinical efficacy .
4.Radioimmuno-tracing of metastatic lymph node for gastric cancer: status quo and progress.
Yunyun PAN ; Hao WANG ; Min FENG ; Wenxian GUAN
Chinese Journal of Gastrointestinal Surgery 2015;18(3):298-300
Lymph node metastasis is one of the factors associated with the prognosis of gastric cancer patients. While precise evaluation of nodal status can promote the personalized surgery and improve prognosis. Although with many unsolved problems and limitations, radioimmune technique can be used to trace gastric cancer and metastatic lymph nodes. With the constant development of monoclonal antibody, genetic engineering antibody, nuclide molecular functional imaging, the radioimmune technique may allow tumor targeting, preoperative imaging, and intraoperative tracing. Therefore, more accurate tumor staging and optimal therapeutic regimen may be possible. This review mainly focuses on the utility of radioimmuno-tracing technique in metastatic lymph node for gastric cancer.
Antibodies, Monoclonal
;
Disease Progression
;
Humans
;
Lymph Nodes
;
Lymphatic Metastasis
;
Neoplasm Staging
;
Prognosis
;
Stomach Neoplasms
5.Visualization analysis of research hotspots and trends of midwifery education in China based on CNKI
Yangguang CHEN ; Jia ZHAO ; Shenmei LI ; Yunyun DAI ; Chuang PAN ; Zili ZHOU
Chinese Journal of Medical Education Research 2023;22(3):331-338
Objective:To analyze the research status, development trend and frontier hotspots of midwifery education in China in recent 20 years.Methods:Based on the topic of "midwifery education" or "midwifery teaching", this paper searched the periodical literatures from 2001 to 2021 on CNKI database, and used CiteSpace5.7R5 software to analyze them visually and generate knowledge map.Results:A total of 548 Chinese papers were included in this study, and the annual number of published papers showed an overall upward trend. The research field of midwifery education in China formed an obvious core team, and there was few cooperation among core author groups. Health Vocational Education, Chinese Nursing Education and Chinese Higher Medical Education were the top three journals. The six topics with the highest frequency were midwifery specialty, midwifery personnel, midwifery education, practice teaching, delivery mode and teaching mode, forming 10 clusters of midwifery education. In recent three years, the research of midwifery education in China has gradually changed into simulation teaching, flipped classroom, postpartum rehabilitation and so on. Conclusion:The research scope of midwifery education in China is wide and has formed an obvious core team, but the correlation is weak and there is less communication and cooperation among the research teams. The research in the field of high-level midwifery education is insufficient. Midwifery educators and researchers should pay enough attention to carry out in-depth research on relevant aspects.
6.The mechanism of poly (ADP-ribose) polymerase on the intestinal mucosal barrier injury in rat model with severe acute pancreatitis through NF-κB signaling pathway
Liangyu MI ; Ziqian WU ; Xinting PAN ; Youdong WAN ; Shaoyan LYU ; Qingyun ZHU ; Jingyu SONG ; Yunyun WANG ; Tianjiao LIN
Chinese Journal of Emergency Medicine 2020;29(5):675-681
Objective:To investigate the effects of poly (ADP-ribose) polymerase-1(PARP-1) in intestinal mucosal barrier injury in rat model with severe acute pancreatitis (SAP).Methods:Twenty healthy male Wistar rats were divided into four groups ( n=5 each group) using a random table method: control, SAP, 3-aminobenzamide (3-AB), and 3-AB control groups. The SAP model was induced by intraperitoneal injection of cerulean with lipopolysaccharide. At 30 min, the rats were treated with the PARP-1 inhibitor, 3-AB, or normal saline,separately. After 12 h, all rats were sacrificed to harvest pancreas tissues, intestines tissues, and blood from the hearts for index detection. Serum amylase (AMY) and interleukin (IL)-6 levels were measured using an automatic biochemical instrument and enzyme-linked immunosorbent assay (ELISA), respectively.The protein expression of PARP-1 and nuclear factor (NF-κB) were measured using Western blot and that of occludin was measured using an immunohistochemical test. One-way analysis of variance was used for comparison of multiple groups of variables. Non-parametric tests of rank conversion were used when variances were not uniform. A P <0.05 was considered statistically significant. Results:Compared to the control group, the following indexes in the SAP group were significantly increased: ascites (with serious hemorrhage and necrosis in the pancreas and disordered intestinal villi),serum AMY and IL-6 levels, and the expression of PARP-1 and NF-κB. However, Occludin expression was significantly decreased. There was no significant difference between 3-AB group and 3-AB control group. Compared to the SAP group, the severity of SAP and pancreatitis-associated intestinal injury was significantly attenuated with the administration of 3-AB. Serum AMY and IL-6 levels were significantly decreased (serum AMY: 1 879.25 ± 736.6 U/L vs 5 569.33 ± 1993.48 U/L; IL-6: 77.98 ± 20.65 pg/mL vs 209.14 ± 79.08 pg/mL, both P<0.05), but the expression of PARP-1 and NF-κB were significantly increased (PARP-1: 1.44 ± 0.09 vs 1.49 ± 0.13; NF-κB: 0.63 ± 0.09 vs 0.96±0.08, both P<0.05). Similarly, Occludin expression was significantly decreased (6.7±1.5 vs 3.2±1.1, P<0.05). Conclusions:Inhibition of PARP-1 has protective effects on SAP associated intestinal mucosal barrier damage. The mechanism may be related to the inhibition of NF-κB signaling pathway and increase intestinal mucosal Occludin protein expression.
7.A case of congenital systemic lipodystrophy with exfoliated xanthoma caused by AGPAT2 gene mutation
Yunyun LUO ; Liyuan ZHANG ; Xinyi WANG ; He LIU ; Hanze DU ; Hui PAN
Basic & Clinical Medicine 2023;43(12):1852-1856
Objective To analyze the clinical characteristics and genotype of a patient with congenital systemic lip-odystrophy(CGL)type 1 associated with exudative xanthoma caused by AGPAT2 gene mutation,and to provide ev-idence for clinical and genetic diagnosis of the disease.Methods Clinical data of the patient such as medical histo-ry,physical examination and laboratory examination were collected.Peripheral venous blood was collected for whole exome sequencing analysis and Sanger sequencing verification,and treatment was provided to patients according to the changes of condition.Results The clinical manifestations of the patient were subcutaneous fat reduction,fatty liver,spleen enlargement,kidney enlargement,high blood sugar and lipids,severe insulin resistance,scattered yellow rash on limbs,which was confirmed as xanthoma.The results of whole exon sequencing showed that the AGPAT2 gene of the patient had a heterozygous nonsense mutation of c.202C>T:p.R68?and c.646A>T:p.K216?,and the former was the pathogenic mutation site.Follow-up therapy covers improvement of lifestyle,low-fat diet and regular exercise.The rashes subsided after active lipid-lowering therapy.Conclusions Apart from typical lipody-strophy,the patient was accompanied by exanthemous xanthoma.No CGL1 patient with exanthemous xanthoma has been reported in the domestic literature database up to now,and the genetic test results showed that there was a c.202C>T heterozygous mutation of AGPAT2 gene.This gene site has not been reported in the literature,and its functional verification needs to be further studied.
8.Protective effect and mechanism of Hirudo on mice with non-alcoholic fatty liver disease
Ziyun WEN ; Qianqian HAN ; Qing LYU ; Liang WEI ; Wenqiang NIE ; Min HONG ; Yunyun PAN
China Pharmacy 2024;35(10):1193-1197
OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease (NAFLD) in mice. METHODS The male ApoE-/- mice were randomly divided into the model group and Hirudo low- dose and high-dose groups (0.45, 0.9 g/kg), with 10 mice in each group; another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically, once a day, for 8 consecutive weeks. In the 13th week, the body weight and liver weight of mice in each group were measured after the last medication, and the liver index was calculated; the serum levels of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β), IL-6, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected; the liver pathomorphological changes were observed; the protein expressions of peroxisome proliferator-activated receptor γ(PPARγ) and silence information regulator type 1 (SIRT1) were detected. RESULTS Compared with the control group, the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells, with significant lipid accumulation; the body weight, liver weight and liver index of the mice, and serum levels of NF-κB, TNF-α, IL-1β, IL-6, TC, TG and LDL-C significantly increased, while the serum level of HDL-C, the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased (P<0.01). Compared with the model group, the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups; the body weight, liver weight and liver index, the serum levels of NF-κB, TNF-α, IL-1β, IL-6, TC, TG and LDL-C decreased significantly, while the serum level of HDL-C, the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly (P<0.05 or P<0.01). CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1, thus having a significant ameliorative effect on NAFLD.