Objective To discuss the clinical efficacy of catheter-directed thrombolysis(CDT)in treating acute pulmonary embolism(APE).Methods A total of 215 patients with APE,who were admitted to the Second Affiliated Hospital of Shandong First Medical University of China,were enrolled in this study.Pulmonary angiography was performed in all the patients.After the location of the thrombus was identified,the pigtail catheter was rotated so as to break the thrombus into small pieces,which was followed by local infusion of thrombolytic agent urokinase to make recanalization of the occluded pulmonary artery.The postoperative clinical symptoms,blood oxygen saturation,mean pulmonary artery pressure,BNP,D-dimer,RV/LV diameter ratio were compared with their preoperative values.PESI scoring was used to evaluate the severity of the pulmonary embolism.Patients with PESI grade-Ⅲ and PESI grade-Ⅳ were classified into medium-risk group,and patients with PESI grade-V were classified into higher-risk group.Results Symptom relief immediately after surgery was observed in 210 patients,complete recanalization of pulmonary artery was achieved in 200 patients,and partial recanalization of pulmonary artery was seen in 15 patients.The preoperative mean pulmonary artery pressure,blood oxygen saturation,BNP,D-dimer,RV/LV diameter ratio were(46.24±5.32)mmHg,(90.36±3.23)％,(8 000.12±750.56)pg/mL,(7.5±2.3)mg/L and(1.63±0.22)respectively;at one week after surgery the above indicators were(26.12±3.36)mmHg,(98.74±2.12)％,(240.35±33.52)pg/mL,(1.75±0.36)mg/L and(1.11±0.13)respectively;the differences were statistically significant(all P＜0.05).In the patients who had symptoms of hemoptysis,shock and syncope before surgery,all these symptoms were completely disappeared in one week after CDT,and the symptoms of dyspnea,chest pain,and palpitations were significantly relieved after CDT,the differences were statistically significant(all P＜0.05).The difference in survival time between different PESI grade groups was statistically significant(P＜0.05).No serious postoperative complications such as severe arrhythmia,cerebral hemorrhage,or gastrointestinal bleeding occurred.Postoperative 3-month CT pulmonary angiography(CTPA)showed that the main pulmonary artery was well visualized and no thrombus-produced filling defect shadow was detected.Conclusion For the treatment of APE,CDT can promptly and rapidly open the obstructed pulmonary artery lumen,restore pulmonary artery hemodynamics,and correct hypoxemia.Therefore,CDT is a safe,effective and quick treatment for APE.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Bone Regeneration ; Cell Differentiation ; Circadian Clocks ; Cryptochromes/metabolism* ; Osteoblasts/metabolism* ; Osteogenesis ; Transcription Factors/metabolism*

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.

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.

OBJECTIVE: To discuss the value of chromosomal microarray analysis (CMA) for the identification of DMD gene deletions during prenatal diagnosis. METHODS: G-banded karyotyping and CMA were performed on fetuses with ultrasonographic soft markers but no family history for Duchenne/Becker muscular dystrophy (DMD/BMD). Denaturing high-performance liquid chromatograghy (DHPLC) was used to detect DMD gene mutations in umbilical cord blood and peripheral blood samples from the mothers. RESULTS: For fetus 1, analysis of amniocytes showed a normal karyotype, while CMA detected a 119 kb deletion at Xp21.1 (32 565 489 - 32 681 461), which encompassed exons 10 to 16 of the DMD gene. The result was confirmed by DHPLC analysis. The mother was found to have loss of heterozygosity in the same region. For fetus 2, karyotyping of amniocytes also showed a normal male karyotype, while CMA detected a 254 kb deletion at Xp21.1 (32 104 604 - 32 358 874), which encompassed exons 41 to 44 of the DMD gene. The same deletion was not detected in the mother. DHPLC analysis confirmed the presence of both deletions. CONCLUSION Two fetuses harboring DMD gene deletions but without a family history were discovered. CMA can improve the efficiency for detecting single gene diseases caused by deletions.
Dystrophin ; genetics ; Exons ; Female ; Fetus ; Gene Deletion ; Humans ; Incidental Findings ; Male ; Microarray Analysis ; Muscular Dystrophy, Duchenne ; genetics ; Pregnancy

We hereby reported a case of ring chromosome 18 complicated by the deletion of 18p11.32p11.31 and 18q21.33q23 diagnosed prenatally by G-banding karyotype and chromosomal microarray analysis (CMA). Ultrasound scan indicated a single umbilical artery and intrauterine growth retardation at the second trimester. The result of G-banding karyotyping was 46, XN, r(18)(p11.3q21.3) and CMA indicated that there was a 3.3 Mb deletion at 18p11.32p11.31 and a 16.9 Mb deletion at 18q21.33q23. All these suggested that the fetus might present with clinical manifestations such as growth retardation, epilepsy, speech delay and growth hormone deficiency after birth, so the couple decided to terminate the pregnancy after genetic counseling.

Objective To explore the current situation and requirements of the health management services among the middle-aged and elderly people in Hainan province for optimizing the health management service pattern. Methods The random sampling method was adopted to perform the survey and analysis on the current situation and requirements of the health management services among 600 middle-aged and elderly people by using the mode of questionnaire combined with interview. Results Totally 575 respondents completed the questionnaire. 43.1% of respondents could correctly understand the concept of health, 40.5% of them thought that "Health is the condition without disease" ;the main ways for getting the health knowledge by these people were mainly joining the intercommunication meeting of health management (97. 2%), phone counseling (94. 4%) and brochures (90.3%) ;the requirements of the health management service mainly focused on the middle age and elderly people aged 45- 59 years old. The most needed health management service items were the mental health service (99.0 %), cultural entertainment service(97.4 %) and health care recovery(84 %). The health management requirements had no statistical difference compared with the gender (x2 = 0. 678, P= 0. 712), cultural degree (x2 = 5. 584, P = 0. 471 ) and medical insurance situation (x2 = 3. 886, P = 0. 420) ;but compared with the age, the difference was statistically significant (x2 = 9. 697, P = 0.04). Conclusion The consciousness of health management among middle age and old people needs to be increased,the health management information platform construction and propaganda promotional efforts should be strengthened, the cooperation between government and enterprise should be strengthened, the pertinence of the health management service should be enhanced and the related policy laws and regulations should be perfected.

In this paper, the patent of traditional medicines of type-2 diabetes mellitus before 2014 were searched, totally 1 229 patent family information were obtained. The patent information including developing trends, geographic distribution, competitive agencies, technical focus, herbs preferences and so on were analyzed. China is in a leader position on the number of applying patent of using traditional medicine to treat type-2 diabetes mellitus, and the main applications were research institutes, universities and pharmaceutical enterprises. Although the views and theo-ries on treatment of type-2 diabetes mellitus are variety and abound, the most frequently used traditional medicines are tonics and heat-clearing. This article reflected the history, clinical treatment way, developments, application of the diabetes traditional drugs after a meta-analysis,efforts to guide a better understanding and further research.

BACKGROUND:Increasing autologous stem cellmobilization is conceived to achieve effectively repair of cardiac ischemic injury. Therefore, it is important to seek a specific and effective mobilization agent. OBJECTIVE:To observe the effects of hypoxia-inducible factor-1α(HIF-1α) on bone marrow mesenchymal stem cellmobilization in myocardial infarction. METHODS:Left anterior descending artery was ligated to establish a rat model of acute myocardial infarction in 90 outbreeding Sprague-Dawley rats, and then the models were randomly divided into three groups. In HIF-1α-antisense oligonucleotide (ASODN) group, HIF-1α-ASODN was infused into the tail vein to restrain the expression of HIF-1αin infarcted ischemic tissue. In HIF-1α-missense oligonucleotide (MSODN) group or control group, an equal volume of HIF-1α-MSODN or saline was injected. RESULTS AND CONCLUSION:After 30 hours and 7 days of modeling, the number of bone marrow mesenchymal stem cells and expression of vascular endothelial growth factor in the peripheral blood of the control group were similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group. After 7 days of modeling, the expressions of HIF-1αprotein, vascular endothelial growth factor protein and mRNA in the ischemic myocardial tissues of the control group were similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group. After 7, 14 and 28 days of modeling, the capil ary density in the ischemic myocardial tissues of the control group was similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group. These findings indicate that after acute myocardial infarction, high expression of HIF-1αexhibits a causal relationship with mobilization of bone marrow mesenchymal stem cells, initiating a series of self-healing process of myocardial tissues.