OBJECTIVETo investigate the effect of adenosine and its agonist on hypoxia-induced right ventricular hypertrophy (RVH) and explore the underlying mechanism.

METHODSFifty-six rats were randomly divided into normoxia group, hypoxia group, and treated hypoxia groups (with different treatments with adenosine, A1 receptor agonist CPA, A2 receptor agonist NECA, CPA plus A1 receptor inhibitor DPCPX, or NECA plus A2B receptor inhibitor MRS1754). The rats except for those in normoxia group were exposed to normobaric chronic hypoxia (9.5%-10.5% oxygen) for 21 days, and the corresponding treatments were administered since the 7th day of hypoxia till day 21 via implantable capsule with a pressure pump. After the treatments, the right ventricles were then removed and weighed for evaluation of hypertrophy, and the expressions of NHE-1 and CnAβ mRNA in the myocardial tissue were detected using RT-PCR.

RESULTSAfter a 21-day hypoxia, the rats showed significantly increased RV/(LV+S) ratio (0.369∓0.033) and RV/BW ratio (0.75∓0.095) compared to those in normoxia group (0.271∓0.010 and 0.59∓0.039, respectively; P<0.001), adenosine treatment group (0.281∓0.022 and 0.65∓0.077, respectively; P<0.001, P=0.025), hypoxia with CPA group (0.313∓0.021 and 0.66∓0.067, respectively P<0.001), and hypoxia with NECA group(0.333∓0.019, and 0.68∓0.074, respectively P<0.001). The NHE-1 and CnAβ mRNA levels in hypoxia group were significantly higher than those in normoxia group, adenosine treatment group, hypoxia with CPA group, and hypoxia with NECA group(P<0.001).

CONCLUSIONAdenosine and its agonist can inhibit hypoxia-induced RVH in rats through the NHE-1/CaN signal pathway.

Adenosine ; agonists ; pharmacology ; Animals ; Hypertrophy, Right Ventricular ; metabolism ; Hypoxia ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Sodium-Hydrogen Exchangers ; metabolism

Objective: To investigate the effects of treatment of hernia sac stump in laparoscopic transabdominal preperitoneal inguinal hernia repair (TAPP) on postoperative seroma. Methods: The prospective study was conducted. The clinical data of 128 male patients with primary indirect inguinal hernia who were admitted to Fujian Medical University Union Hospital from October 2017 to March 2019 were selected. Patients were divided into two groups by random number method. Patients in experimental group had hernia sac stump sutured and fixed at the lower margin of rectus abdominis after transection of hernia sac in TAPP, and patients in control group had hernia sac stump free in the abdominal cavity after dissection and transection of hernia sac in TAPP. Observation indicators: (1) surgical situations; (2) follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect the incidence of postoperative seroma, incision infection, chronic pain, and hernia recurrence up to June 2019. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was done using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was done using the Mann-Whitney U test. Count data were described as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test. Results: A total of 128 male patients were screened for eligibility, including 60 patients in the experimental group and 68 patients in the control group. The 128 patients were aged from 47 to 74 years, with an average age of 61 years. (1) Surgical situations: operation time and hospital expenses were (102±34)minutes and (12 813±2 390)yuan for the experimental group, and (97±30)minutes and (12 125±2 205)yuan for the control group, respectively, showing no significant difference between the two groups (t=0.907, 1.685, P>0.05). (2) Follow-up: all the 128 patients received follow-up. There were 8 cases of seroma in both the experimental group and the control group, with no significant difference between the two groups (χ²=0.072, P>0.05). The extraction volume of patients with seroma was 20 mL (range, 4-31 mL) in the experimental group, and 43 mL (range, 23-98 mL) in the control group, showing a significant difference between the two groups (Z=-2.013, P<0.05). There was no incision infection, chronic pain or hernia recurrence in 3 months after operation in patients with seroma of either experimental group or control group. Conclusions During TAPP, suture and fixation of the hernia sac stump to the lower edge of rectus abdominis and free hernia sac stump in the abdominal cavity after dissection and transection of hernia sac can effectively repair indirect inguinal hernia. The former method can reduce the extraction volume of seroma after operation.

OBJECTIVETo investigate the relationship between the quality of life (QOL) and disability level in patients with occupational disease and to investigate the influencing factors for QOL.

METHODSA total of 255 patients with occupational disease were selected from three specialized hospitals dedicated to occupational disease and the department of occupational medicine of one comprehensive hospital using cluster sampling from December 2013 to May 2014. A survey was carried out using WHOQOL-BREF and general questionnaire (including disability level), and statistical analysis was also performed using t test, F test, analysis of variance, and multivariate stepwise regression analysis.

RESULTSThe QOL scores of patients with occupational diseases, from high to low, were social domain (11.48 ± 2.86), psychological domain (10.60 ± 2.28), physiological domain (10.54 ± 1.65), and environmental domain (10.50 ± 2.55), scores of which were significantly lower than the normal levels (P<0.05). QOL showed no significant differences between patients with occupational diseases of different disability levels (P>0.05). Also, QOL showed no significant differences between stage I, II and III patients with pneumoconiosis (P>0.05). The patients with pneumoconiosis were divided into mild, moderate, and severe groups, and the QOL scores of patients with mild pneumoconiosis in psychological and environmental domains were significantly higher than those of the patients with moderate or severe pneumoconiosis (P< 0.05). Patients with occupational poisoning was divided into mild, moderate and severe groups, and the three groups showed no significant differences in QOL score (P>0.05). Multivariate regression analysis showed that the QOL score of each domain was mainly influenced by the degree of lung injury, complications, course of disease, age of onset, income, and employment status.

CONCLUSIONThe QOL of patients with occupational disease is significantly reduced, and disability level cannot accurately reflect their QOL. The treatment of patients with occupational disease should focus on their complications, and at the same time QOL should also be improved.

Disability Evaluation ; Humans ; Occupational Diseases ; psychology ; Pneumoconiosis ; psychology ; Poisoning ; psychology ; Quality of Life ; Regression Analysis ; Surveys and Questionnaires

Objective:To evaluate the role of nuclear factor NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in atorvastatin-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Twenty-four healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divide into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal I/R group (I/R group), atorvastatin group (ATV group) and atorvastatin+ Nrf2 inhibitor ML385 group (AM group). Intestinal I/R was produced by occlusion of superior mesenteric artery for 45 min followed by reperfusion.In ATV and AM groups, atorvastatin 10 mg/kg was given by gavage for 3 consecutive days daily at 3 day before establishment of the model, while the equal volume of normal saline was given by gavage in S and I/R groups.Nrf2 inhibitor ML385 30 mg/kg was intraperitoneally injected at 1 h before establishment of the model in group AM.The mice were sacrificed at 2 h of reperfusion, and intestine tissues were obtained for examination of the pathological changes of intestinal tissues (with a light microscope) which were scored according to Chiu, for determination of wet/dry weight ratio (W/D ratio), for detection of the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) (by xanthine oxidase method and thiobarbituric acid condensation method) and for determination of the expression of Nrf2 and HO-1 (by Western blot). Results:Compared with S group, the Chiu score, W/D ratio and MDA content were significantly increased, the activity of SOD was decreased, and the expression of Nrf2 and HO-1 was up-regulated in the other 3 groups ( P<0.05). Compared with the group I/R, the Chiu score, W/D ratio and MDA content were significantly decreased, the SOD activity was increased, and the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological changes were significantly attenuated in group ATV, and no significant change was found in the parameters mentioned above in AM group ( P>0.05). Compared with the group ATV, the Chiu score, W/D ratio and MDA content were significantly increased, the SOD activity was decreased, the expression of Nrf2 and HO-1 was decreased ( P<0.05), and the pathological changes were significantly aggravated in group AM. Conclusion:The mechanism by which atorvastatin reduces intestinal I/R injury is related to activating Nrf2/HO-1 signaling pathway in mice.

Objective:To evaluate the role of peroxidase proliferator-activated receptor γ (PPARγ)/nuclear factor kappa B (NF-κB) signaling pathway in sodium butyrate-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty-two SPF-grade healthy adult male C57BL/6J mice, aged 7-9 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (IIR group), sodium butyrate group (NaB group) and PPARγ inhibitor GW9662 group (GW9662 group). The model of intestinal I/R was established by occlusion of superior mesenteric artery for 45 min followed by 2-h reperfusion in anesthetized animals.GW9662 2 mg/kg was intraperitoneally injected at 1 h before ischemia in GW9662 group, and sodium butyrate 500 mg/kg was intraperitoneally injected at 30 min before ischemia in NaB and GW9662 groups.Blood samples were obtained via cardiac puncture at 2 h of reperfusion, and the animals were then sacrificed.The intestinal tissues were removed for determination of diamine oxidase (DAO), tumor necrosis factorα (TNF-α) and interleukins 6 (IL-6) concentrations in serum (by enzyme-linked immunosorbent assay) and the expression of PPAR and NF-κB p65 (by Western blot). The damage to intestinal mucous membrane was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score was significantly increased, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were increased, expression of PPARγ was down-regulated, and expression of NF-κB p65 was up-regulated in group IIR ( P<0.05). Compared with group IIR, the Chiu′s score, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were decreased, and expression of PPARγ was up-regulated in group NaB, and expression of NF-κB p65 was up-regulated in NaB and GW9662 groups ( P<0.05). Compared with group NaB, the Chiu′s score, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were increased, and expression of PPARγ was down-regulated, and expression of NF-κB p65 was up-regulated in group GW9662 ( P<0.05). Conclusion:The mechanism by which sodium butyrate reduces intestinal I/R injury may be related to activating PPARγ/NF-κB signaling pathway and inhibiting inflammatory responses in mice.

Objective:To investigate the effect of atorvastatin preconditioning on intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) signaling pathway.Methods:Twenty-four healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), I/R group, atorvastatin preconditioning group (A group), atorvastatin plus PI3K inhibitor LY294002 group (AL group). Atorvastatin 10 mg/kg was given by intragastric gavage for 3 consecutive days in A and AL groups, and in addition LY294002 0.3 mg/kg was intraperitoneally injected at 30 min before the last administration of atorvastatin in AL group.Intestinal I/R was produced by occlusion of superior mesenteric artery (SMA) for 45 min followed by 2 h reperfusion in anesthetized mice.The superior mesenteric artery was only isolated but not clamped in S group.The mice were sacrificed at the end of reperfusion, and small intestinal tissues were taken for determination of the pathological changes with a light microscope after HE staining and for determination of wet to dry weight ratio(W/D ratio) and expression of PI3K, phosphorylated Akt (p-Akt), autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3Ⅰ (LC3Ⅰ) and LC3Ⅱ.The intestinal damage was assessed and scored according to Chiu.The ratio of LC3Ⅱ expression to LC3Ⅰ expression (LC3Ⅱ/LC3Ⅰ) was calculated. Results:Compared with S group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in I/R, A and AL groups ( P<0.05). Compared with I/R group, Chiu′s scores and W/D ratio were significantly decreased, the expression of PI3K and p-Akt was up-regulated, the expression of Beclin-1 was down-regulated, and LC3Ⅱ/LC3Ⅰ ratio was decreased in A group ( P<0.05). Compared with A group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in AL group ( P<0.05). Conclusion:Atorvastatin preconditioning can mitigate intestinal I/R injury in mice, and the mechanism is related to activating PI3K/Akt signaling pathway and inhibiting the level of autophagy.

Objective　To observe the incidence of white matter hyperintensities （WMHs） and the distribution of right to left shunt （RLS） in migraine patients，and to explore whether WMHs is related to RLS. Methods　106 patients with migraine were selected as the research objects. The basic data and clinical information of migraine were collected. The WMHs were evaluated by cranial MRI. The RLS was diagnosed and graded by transcranial Doppler （TCD） bubbles test. The correlation between WMHs and RLS was analyzed. Results　Among 106 migraine patients，33 （31.1%） were in WMHs+ group and 73 （68.9%） in WMHs- group. The total positive rate of RLS was 48.1% （51/106）. The distribution of different shunt levels was as follows：grade Ⅰ shunt in 27 cases （25.5%），grade Ⅱ shunt in 4 cases （3.8%），grade Ⅲ shunt in 6 cases （5.6%），grade Ⅳ shunt in 14 cases （13.2%）. In "WMHs+" group，there were 5 cases of grade Ⅰ shunt，1 case of grade Ⅱ shunt，3 cases of grade Ⅲ shunt and 10 cases of grade Ⅳ shunt；in "WMHs-" group，there were 22 cases of grade Ⅰ shunt，3 cases of grade Ⅱ shunt，3 cases of grade Ⅲ shunt and 4 cases of grade Ⅳ shunt. Compared with "WMHs+" group and "WMHs-" group，there was no statistical difference in the overall positive rate of bubbles test between the two groups （P>0.05，χ2=1.719），but the large shunt rate of "WMHs+" group was significantly higher than that of "WMHs-" group （P<0.01，χ2=13.188）. Conclusion　There is no significant correlation between WMHs and RLS in migraine patients，but large RLSs will increase the risk of WMHs in migraine patients.

Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.

AIM: To evaluate the effect of SLC7A11 in dexmedetomidine pretreatment induced reduction of ferroptosis caused by intestinal ischemia-reperfusion (II/R) injury in mice. METHODS: Twenty-four healthy meal SPF C57BL/6J mice, aged 8 weeks, weighing 22-25 g, were randomly divided into Sham operation group (S group), intestinal I/R group (II/R group), dexmedetomidine group (DEX group) and dexmedetomidine plus SLC7A11 inhibitior group (DIKE group), with 6 mice in each group. Intestinal ischemia was induced by occluding the superior mesenteric artery for 45 min followed by 30 min of reperfusion to establish the model of II/R injury. In DEX and DIKE groups, Dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before clamping the superior mesenteric artery. The same amount of normal saline was injected in the S group and the II/R group. In DIKE group, SLC7A11 inhibitior Imidazole ketone erastin 50 mg/kg was intraperitoneally injected at 90 min before ischemia. Mice were sacrificed 30 min after reperfusion, and small intestinal tissues in length 5 cm away from the ileocecal valvum were obtained for microscopic examination of pathological changes of intestinal mucosa and for determination of contents of Fe

AIM: To observe the effect of paricalcitol on intestinal ischemia-reperfusion injury, and to explore the relationship with HMGB1/TLR4/NF-κB signaling pathway. METHODS: Twenty-four SPF-grade healthy adult male C57BL/6J mice were divided into 4 groups (n=6) by random number table: sham operation group (S group), paricalcitol pretreatment+sham operation group (SP group), intestinal ischemia-reperfusion group (IR group) and paricalcitol ischemic preconditioning group (P group). S group and SP group were separated the superior mesenteric artery, IR group and P group were clamped the superior mesenteric artery for 45 minutes and then followed by reperfusion for 2 hours to establish the intestinal ischemia-reperfusion model; SP group and P group were intraperitoneally injected with 0.3 μg/kg paricalcitol 24 hours before surgery, and the other two groups were given equal volume of normal saline. The mice were sacrificed at 2 h after reperfusion, and the intestinal tissue was obtained 5 cm from the terminal ileum. The pathological results were observed under light microscope. The intestinal mucosal injury was scored according to the Chiu's scoring standard. The intestinal tissue diamine oxidase (DAO) and tumor were detected by ELISA. Necrosis factor α (TNF-α) and interleukin 6 (IL-6) content; Western blot was used to detect the expression levels of HMGB1, TLR4 and NF-κB p65 protein in small intestine tissues.RESULTS: Compared with S group and SP group, Chiu's score was increased, the expression of Dao, TNF-α and IL-6 were increased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein increased significantly in IR group (P< 0.05); Compared with IR group, Chiu's score was decreased, the expression of Dao, TNF-α and IL-6 were decreased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein decreased significantly in P group (P< 0.05). CONCLUSION: Paricalcitol can alleviate intestinal ischemia-reperfusion injury by inhibiting HMGB1/TLR4/NF-κB signaling pathway and playing an anti-inflammatory role.