[Current status of parental decision-making of childhood 13-valent pneumococcal conjugate vaccine immunization and related factors in China].

Objective: To analyze the relationship between health belief and the stages of parental decision-making on childhood 13-valent pneumococcal conjugate vaccine (PCV13) immunization in China. Methods: Cross-sectional multistage survey sampling method was used to select study subjects. The study subjects were parents who were aged 20-45 years and had one and more children ≤5 years old in three cities in China. A self-administered questionnaire designed based on health belief model was used to collect the information. Multinomial logistic regression analysis was used to assess the relationships between perceived susceptibility, perceived severity of illness, perceived effect of PCV13 and stages of parental decision-making on childhood PCV13 immunization. Results: A total of 1 716 valid questionnaires were returned (89.33%). The average age of the study subjects was (35.33±4.95) years, and 79.60% of them were women. In the study subjects, 48.31% had in action, 21.79% were in contemplation and 29.90% were in pre-contemplation. The multinominal logistic regression analysis indicated that high perceived susceptibility (OR=0.14, 95%CI:0.09-0.22; OR=0.54, 95%CI:0.39-0.76), high perceived severity of illness (OR=0.55, 95%CI:0.42-0.73), and high perceived effect of PCV13 (OR=0.27, 95%CI:0.18-0.40; OR=0.51, 95%CI:0.32-0.81) were significantly lower in those who were in contemplation or pre-compared with those who had in action. For study subjects with low perceived susceptibility, high perceived effect of PCV13 might decrease the probabilities of contemplation (OR=0.53, 95%CI:0.32-0.87) and pre-contemplation (OR=0.27, 95%CI:0.18-0.41). For those with high perceived susceptibility, perceived severity of illness might decrease the probability of contemplation (OR=0.43, 95%CI:0.23-0.82). Conclusions: Childhood PCV13 vaccination willingness and level is low in China. It is important to pay greater attention to the intervention on health belief in child parents, such as perceived effect of PCV13, perceived severity of illness, and perceived susceptibility, in health policy development and health promotion.

[Clinical efficacy of resection of extramedullary subdural tumor in thoracic spinal canal via muscle-pedicle open-door laminoplasty approach].

In order to evaluate the efficacy of resecting extramedullary subdural tumors, located in the thoracic spinal canal, via the muscle-pedicle open-door laminoplasty approach, clinical data of fifteen patients with thoracic spinal tumors admitted to the Department of Spinal Surgery in the Affiliated Hospital of Qingdao University from December 2018 to June 2021 were analyzed retrospectively. All patients received surgical treatment to remove the tumors via the muscle-pedicle open-door laminoplasty approach. The clinical data of the patient was recorded. The Japanese Orthopedic Association (JOA) score, the thoracic kyphosis angle in the standing position before and after the operation, and the visual analog score (VAS) of thoracic back incision pain before and after the operation were compared. CT scan was performed three months after the surgery and at the last follow-up to measure the healing of the lamina. In addition, MRI was used to detect the healing of the posterior ligament at the last follow-up. The tumors of all fifteen patients were completely removed, the operating time was (91±15) minutes, blood loss was (117±56) ml. Cerebral spinal fluid leakage occurred in three patients, but the incisions healed smoothly following compression and no complication was observed. All patients were followed-ups for more than 6 months. The VAS score of thoracic back incision pain was (3±1.3) points at three days post operation and it dropped to (1.3±0.9) points three months post-operation. The JOA score improved significantly after the operation, it was (11.9±2.4) points before operation, and it was (14.0±1.6) points three months post operation and increased to (16.1±0.7) points at the last follow-up (both P<0.001). The Cobb angle was 10.1°±5.3° before the operation and it was 10.4°±6.2° at the last follow-up (P=0.420). Three months after operation, partial callus formation or even complete healing on the muscle pedicle side was observed on the CT scans of all patients. At the last follow-up, CT scans showed complete healing on the muscle pedicle side. There were different degrees of sclerosis and healing on the open-door side. There was no necrosis, displacement, or secondary spinal canal stenosis in any vertebral lamina. It indicated that the muscle-pedicle open-door laminoplasty approach is an effective way to resection extramedullary subdural tumors located in the thoracic spinal canal.

Role of HMGB1 in the formation of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism.

Acute pulmonary embolism (PE) may be a common but fatal condition in several countries; in untreated or inadequately therapeutic PE patients, is a commonly occurring long-term complication affecting patient survival treatment and prognosis, contributing to right heart disease and may even be fatal. To date, the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) due to acute pulmonary embolism remains unclear; hence, there is an immediate demand for medications that are directly aimed at both preventing and managing the progression of CTEPH. Previous studies have shown that the inflammatory response is associated with thrombosis and the development of pulmonary cardiovascular disease. High-mobility Group B 1 (HMGB1), a damage-associated molecular pattern (DAMP), is involved in deep vein thrombosis and inflammatory reactions, vascular remodeling, and thrombosis in pulmonary hypertension. Therefore, we hypothesized that HMGB1 participates in the process of CTEPH development after acute PE. This paper details the dynamic changes in HMGB1 and the relationship between HMGB1 and the advancement of CTEPH after acute PE to better understand the pathogenic mechanisms and potential clinical applications.

[Dynamic changes of axial length, corneal refractive power, and refractive state after cataract surgery in infants].

Objective: To investigate the changes of axial length, corneal refractive power, and refractive state in infants with congenital cataract surgery. Methods: Retrospective cohort study. Medical records of 103 patients who underwent congenital cataract surgery in the Eye Hospital of Wenzhou Medical University Hangzhou Branch from January 1, 2015 to December 31, 2018 were reviewed. There were 61 boys and 42 girls in the study. The mean age at the surgery of 103 congenital cataract patients was (3.95±1.94) months. In patients receiving bilateral cataract surgery, only the left eye was selected for analysis. The patients were followed up for at least 1 year. The patients were divided into the groups of <4 months old and 4-12 months old according to the age at cataract surgery. The change in the axial length, corneal refractive power, and refractive state of each patient at 1 year after surgery was analyzed. Independent sample t-test, one way variance analysis and simple linear regression were used for statistical analysis. Results: There were 71 cases of bilateral cataract, including 33 in the group of <4 months old and 38 in the group of 4-12 months old, and 32 cases of unilateral cataract, including 17 in the group of <4 months old and 15 in the group of 4-12 months old. The change in the axial length of bilateral cataract children in the <4-month-old group was (2.46±1.33) mm at 1 year after surgery, which was greater than (1.52± 1.00) mm in the group of 4-12 months old (t=3.21; P<0.01). In the same surgery age group, there was no significant difference in the change of axial length among bilateral cataract eyes, unilateral cataract eyes and the contralateral eyes at 1 year after surgery (both P>0.05). One year after surgery, the axial length of the eyes in patients with bilateral cataract, the affected eyes and the fellow eyes in patients with unilateral cataract all was highly correlated with the logarithm of the actual age (r=0.68, 0.52, 0.73; all P<0.01). The corneal refractive power showed a decreased trend with the increase of age. The change in the corneal refractive power of the bilateral cataract children in the <4-month-old group at 1 year after surgery was (1.43±2.87) D, and in the group of 4-12 months old was (0.68±2.10) D, but the difference was not statistically significant (P>0.05). The chang in spherical equivalent of bilateral cataract children was (2.02±2.60) D in the <4-month-old group, greater than that in the group of 4-12 months old [(0.69±1.89) D; t=2.15; P<0.05]. The change of spherical equivalent one year after surgery in 4-12 months group, unilateral cataract eyes was significantly greater than that of bilateral cataract eyes [(2.05±0.95) D vs. (0.69±1.89) D; t=2.49; P<0.05]. The spherical equivalent of both bilateral and unilateral cataract children was highly correlated with the actual age (r=-0.51, -0.54; both P<0.01). Conclusions: The axial length is increased, the corneal refractive power is decreased, and the spherical equivalent is decreased at 1 year after surgery for congenital cataract in infants. The younger the age at cataract surgery, the greater the change in the axial length, myopia drift, and corneal refractive power. (Chin J Ophthalmol, 2021, 57: 34-40).

[Cytological analysis of lymphoblastic lymphoma/acute lymphoblastic leukemia in serous effusion].

Objective: To study the diagnostic clues and significance in serous effusion cytology associated with lymphoblatic lymphoma/acute lymphoblastic leukemia (LBL/ALL). Methods: Forty-five serous effusion specimens with final diagnosis of LBL/ALL were collected from August 2011 to December 2019 at the First Affiliated Hospital of Zhengzhou University. All cases were reviewed for their clinical profiles, cytomorphologic features and ancillary studies. Cell blocks and immunocytochemistry were prepared in 22 cases; flow cytometric immunophenotyping was performed in three cases and gene rearrangement analysis (T-cell recepter, TCR and immunoglobulin, Ig) was performed in five cases. Results: Among the 45 cases, there were 35 males and 10 females with male to female ratio of 3.5∶1.0. The median age was 15 years. Mediastinal mass was the initial presentation in 39 patients (86.7%) and high LDL level were observed in 34 patients (75.6%). Microscopically, the majority of the specimens (86.7%) were hypercellular. The smears demonstrated dispersed lymphoblasts that were predominantly small to intermediate in size with scanty basophilic cytoplasm and irregular or convoluted nuclei with fine chromatin condensation and inconspicuous nucleoli. Mitoses were frequently observed. Karyorrhexis and apoptosis were seen in all cases. By immunophenotyping, TdT was expressed in 19 cases (86.4%) and CD99 in 20 cases (90.9%). Ki-67 expression varied from 65% to 95%. Flow cytometry in three cases demonstrated positivity for TdT, CD2, CD3 and CD7. Monoclonal TCR gene rearrangement was found in 4 of 5 cases, and both monoclonal TCR and Igκ gene were found in 1 case. Conclusions: In LBL/ALL, primary diagnosis could be made basing on clinical features (younger male patients with a mediastinum mass) and cytomorphology (monotonous, small to medium sized lymphoid cells with prominent irregular nuclei, fine chromatin and frequent mitoses, karyorrhexis and apoptosis). If immunocytochemistry and other ancillary studies are performed, the accuracy and reliability of the results could be improved.

Hierarchical Construction of Higher-Order Exceptional Points.

The realization of higher-order exceptional points (HOEPs) can lead to orders of magnitude enhancement in light-matter interactions beyond the current fundamental limits. Unfortunately, implementing HOEPs in the existing schemes is a rather difficult task, due to the complexity and sensitivity to fabrication imperfections. Here we introduce a hierarchical approach for engineering photonic structures having HOEPs that are easier to build and more resilient to experimental uncertainties. We demonstrate our technique by an example that involves parity-time symmetric optical microring resonators with chiral coupling among the internal optical modes of each resonator. Interestingly, we find that the uniform coupling profile is not required to achieve HOEPs in this system-a feature that implies the emergence of HOEPs from disorder and provides resilience against some fabrication errors. Our results are confirmed by using full-wave simulations based on Maxwell's equation in realistic optical material systems.

LncRNA NEAT1 regulates proliferation, apoptosis and invasion of liver cancer.

OBJECTIVE: The occurrence and progression of hepatocellular carcinoma (HCC) is a multi-step complex process and the exact molecular mechanisms remain to be elucidated. LncRNA NEAT1 is involved in tumorigenesis and progression. However, the role of LncRNA NEAT1 in HCC remains unclear. PATIENTS AND METHODS: The tumor tissues and adjacent tissues of HCC patients were collected and LncRNA NEAT1 expression was detected by Real time PCR. The hepatoma cell line HepG2 was cultured and transfected with lnc RNA NEAT1 siRNA or lnc RNA NEAT1 plasmid followed by analysis of LncRNA NEAT1 expression, cell proliferation by MTT assay, as well as Caspase 3 activity. In addition, cell apoptosis and cell cycle were assessed by flow cytometry and cell invasion was measured by transwell chambers. The expression of EGFR, Bax and Bcl-2 was detected by Western blot. RESULTS: LncRNA NEAT1 expression was significantly increased in HCC tissues compared with adjacent tissues (p < 0.05). Compared with the siRNA group, transfection of lncRNA NEAT1 siRNA into HepG2 cells significantly inhibited cell proliferation, increased Caspase 3 activity and apoptosis, reduced cell invasion, as well as arrested cell cycle (p < 0.05). Meanwhile, lncRNA NEAT1 siRNA also significantly decreased Bcl-2 and EGFR expression and increased Bax expression (p < 0.05). Transfection of lncRNA NEAT1 plasmid in hepatoma cells HepG2 reversed the above changes, compared with vector group, the differences were statistically significant (p < 0.05). CONCLUSIONS: LncRNA NEAT1 expression is increased in liver cancer tissues. Down-regulation of LncRNA NEAT1 can inhibit EGFR expression and promote hepatoma cell apoptosis, inhibit cell cycle, thus inhibiting tumor proliferation and invasion.

[Investigation and analysis on occupational hazard factors exposure to the female workers in Gansu province].

Objective: To investigation on the occupational hazardous factors exposed to the female workers, from 14 prefectures and municipalities in Gansu province. Methods: The survey was conducted from June to October 2015. A total of 8 538 female employees from 30 enterprises in 14 prefectures and cities of the province were selected by cluster sampling method. The occupational hazard factors were investigated and analyzed statistically. Results: The survey found that the proportion of female workers in Gansu province who are exposed to chemical and physical harmful factors at the same time is relatively large. Most female workers are exposed to 2-4 occupational hazards, and women who are exposed to 3 and 4 chemical harmful factors account for 28.8 % and 38.0 %, respectively. Women workers who were exposed to two or three physical factors at the same time accounted for 59.44 per cent, while 61.5% were exposed to two biological factors at the same time. The number of female workers exposed to two or three physical factors at the same time and the number of four and five physical factors at the same time after being tested by χ(2). The difference is statistically significant (χ(2)= 8.17, P<0.05) . The difference in the number of female workers who simultaneously exposed 3 and 4 chemical factors and simultaneously exposed 2 and 5 or more chemical factors is statistically significant (χ(2)=11.26, P<0.05) . There was no significant difference in the exposure of female workers to biological factors. Conclusion: This survey shows that the exposure of female workers in Gansu Province to occupational hazards is not optimistic. We should strengthen enterprise supervision and improve the working environment and conditions of female workers.

[Resection of lumbar nerve sheath tumors via muscle-pedicle open-door laminoplasty approach].

Objective: To evaluate the efficacy and safety of resection of lumbar nerve sheath tumors via muscle-pedicle open-door laminoplasty approach. Methods: From March 2016 to June 2018, 6 patients (4 males and 2 females, average age (45±14) years) with lumbar spinal nerve sheath tumors received surgical treatment via muscle-pedicleopen-door laminoplasty approach in the Department of Spinal Surgery, the Affiliated Hospital of Qingdao University. The operation time, blood loss, cerebral spinal fluid (CSF) leakage, and pre- and post-operative Oswestry Disability Index (ODI) and low back and leg pain visual analogue scale (VAS) were recorded for all patients. Cobb angle of lumbar lordosis was measured on the standing lateral X-ray before and 6 months after surgery. Bone fusion was observed in computed tomography at six months after surgery. Results: Total tumor resection was achieved in all the 6 patients. The operation time was from 76 to 117 minutes (average, (102±15) minutes). The blood loss was from 160 to 280 ml (average, (256±24) ml). No CSF leakage was observed in this cohort.All patients were followed up for more than 6 months. ODI and VAS for low back and leg pain were much better at one month after operation than those before the operation(t=7.70, 8.63,11.31, all P<0.05). The Cobb angle of lumbar lordosis before operation and at six months after the operation were comparable in all six patients(t=0.70, P>0.05). Bone fusion was observed in computed tomography at six months after surgery. No bone necrosis or absorption, no lamina dislodgement or spinal stenosis was occurred. Conclusions: The muscle-pedicle open-door laminoplasty approach is proved effective and safe to incise nerve sheath tumors in the lumbar spine. Some blood supply of lamina can be kept intact to accelerate bone fusion.

[Study on insecticide resistance of Culex pipiens pallens in southwest region of Shandong Province].

OBJECTIVE: To explore the sensitivity of Culex pipiens pallens to common chemical insecticides in the southwestern region of Shandong Province, so as to provide a theoretical basis for the development of reasonable and effective mosquito control measures. METHODS: The resistance of Cx. pipiens pallens larvae to 5 chemical insecticides, such as cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate were tested by using the WHO biological test method in 2018, and the co-toxicity coefficients after compounding the above-mentioned insecticides were tested by using a drug compounding method. RESULTS: The resistance indexes of Cx. pipiens pallens to cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate in 3 cities were 144.43-557.54, 118.17-445.33, 6.44-19.00, 2.37-8.10, and 0.88-2.98, respectively, and expect the difference between the DDVP resistances of Cx. pipiens pallens in Jining City and Heze City was not statistically significant (P > 0.05), all the other differences were statistically significant (all P < 0.05). The synergistic coefficients of cypermethrin + DDVP, cypermethrin + propoxur, DDVP + acetofenate, and propoxur + acetofenate were 199.58 - 456.95, 190.56 - 292.37, 123.32 - 319.24, and 192.31 - 367.32, respectively. The lower synergism was observed by using the mixture of DDVP + propoxur (synergistic coefficient: 99.87-108.36) . CONCLUSIONS: After decades of chemical control, Cx. pipiens pallens in the southwestern region of Shandong Province has produced different degrees of resistance to common chemical insecticides. Therefore, comprehensive control measures should be taken to control mosquito breeding and prevent the development of insecticide resistance.

Expression of Ski and its role in astrocyte proliferation and migration.

Ski, as an evolutionarily conserved protein, is a versatile transcriptional regulator which widely distributes in various tissues and species. Recently, we have demonstrated for the first time that Ski was strikingly up-regulated in reactive astrocytes after spinal cord injury (SCI) in vivo, which indicates that maybe Ski is a new molecule that controls astrocytes' biological properties after SCI. However, the accurate distributions and functions of Ski in astrocytes after central nervous system (CNS) injury are still unclear. Astrocytes were collected from rats' cerebral cortex. To elucidate the expression and role of Ski in reactive astrocytes, we performed an activated astrocytes model induced by LPS and scratch injury in vitro. Our results showed that Ski gradually increased and reached a peak at 4days, then declined at 6days after induction by LPS. Up-regulation of Ski was accompanied with the increase in proliferation-related proteins including PCNA, CDK4 and CyclinD1. Furthermore, immunofluorescent staining analysis also demonstrated a highly positive relationship between Ski and GFAP, PCNA in astrocytes. These results indicated that Ski might play an important role in astrocyte proliferation. To further explore the role of Ski, astrocytes were transfected with Ski-specific small interfering RNA (siRNA). We found that the primary activated astrocytes' proliferation decreased significantly after transfection with Ski-specific siRNA. Surprisingly, Ski knockdown also weakened the primary astrocyte migration. Based on the above, we could conclude that Ski might play a crucial role in astrocyte proliferation and migration. This discovery might contribute to a promising therapeutic intervention in CNS injury.

[The clinical characteristics and surgical treatment strategy of acute gangrenous cholecystitis after biliary tract stenting].

Objective: To analysis of the possible cause and surgical diagnosis and treatment strategies of acute gangrenous cholecystitis (AGC) after biliary stent drainage. Methods: The clinical data of 273 patients who received biliary stent drainage in Beijing Chaoyang Hospital from January 2015 to March 2016 were analyzed retrospectively. Among them, 22 patients who underwent surgical treatment were divided into two groups: 9 cases of AGC group and 13 cases of non-AGC group. The risk factors of AGC and surgical approach were analyzed. Result: All 22 patients underwent laparoscopic surgery. In AGC group, 1 patient with toxic shock died of multiple organ viscera function failure caused by infection, and 1 patient with gallbladder triangle inflammatory adhesion suffered from biliary leakage. The postoperative pathology of 2 patients was acute gangrenous cholecystitis. Non-AGC group had no death, bile duct injury and bleeding, with postoperative pathology of chronic cholecystitis. Patients were followed up for 2 month to restore well, without biliary calculi residual. Operation time, intraoperative blood loss, hospitalization days and hospitalization expenses of AGC group were higher than those of non-AGC group. Conclusion: The advocated AGC after biliary stent drainage should actively surgery after early diagnosis and endoscopic therapy should not be repeated. Laparoscopic surgery is a safe and effective treatment for AGC after carotid stenting.

Extracellular DNA traps released by acute promyelocytic leukemia cells through autophagy.

Acute promyelocytic leukemia (APL) cells exhibit disrupted regulation of cell death and differentiation, and therefore the fate of these leukemic cells is unclear. Here, we provide the first evidence that a small percentage of APL cells undergo a novel cell death pathway by releasing extracellular DNA traps (ETs) in untreated patients. Both APL and NB4 cells stimulated with APL serum had nuclear budding of vesicles filled with chromatin that leaked to the extracellular space when nuclear and cell membranes ruptured. Using immunofluorescence, we found that NB4 cells undergoing ETosis extruded lattice-like structures with a DNA-histone backbone. During all-trans retinoic acid (ATRA)-induced cell differentiation, a subset of NB4 cells underwent ETosis at days 1 and 3 of treatment. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly elevated at 3 days, and combined treatment with TNF-α and IL-6 stimulated NB4 cells to release ETs. Furthermore, inhibition of autophagy by pharmacological inhibitors or by small interfering RNA against Atg7 attenuated LC3 autophagy formation and significantly decreased ET generation. Our results identify a previously unrecognized mechanism for death in promyelocytes and suggest that ATRA may accelerate ET release through increased cytokines and autophagosome formation. Targeting this cellular death pathway in addition to conventional chemotherapy may provide new therapeutic modalities for APL.

[Characteristics of tinnitus related to idiopathic suddensensorineural hearing loss in 272 patients].

Objective:To investigate the characteristics of sudden sensorineural hearing loss (SSHL) patients with tinnitus.Method:Two-hundred and seventy two SSHL patients with tinnitus underwent evalution through Tinnitus Handicap Inventory(THI) and Tinnitus Questionnaire(TQ).Demographic data and tinnitus characteristics were analyzed.Result:In 272 patients,41.6% of patients suffered from low frequency tinnitus,2.0% with medium frequency tinnitus,56.4% with high frequency tinnitus.There were 79% patients whose tinnitus were continous,while 21% were intermittent;From the view point of daily life compromising,37.4% were minor,44.8% were moderate,17.8% were serious.The most important factors that deteriorate tinnitus were bad sleep,noise,life pressure and tiredness.Conclusion:There were individual differences among patients with sudden deafness and tinnitus.Enough evaluation should be made to decrease the infection of tinnitus.

Extrication process of chlorogenic acid in Crofton weed and antibacterial mechanism of chlorogenic acid on Escherichia coli.

Crofton weed is a perennial herb and a biological intruding species. The present study firstly used the orthogonal test to compare the differences in extraction of chlorogenic acid in leaves and stems of Crofton weed by using three kinds of solvents, namely water, ethanol and ethyl acetate. The best effect was found by using ethonolic extraction of chlorogenic acid in Crofton weed. Further, by choosing Escherichia coli as test object, in-vitro antibacterial test was conducted to study the antimicrobial activities of chlorogenic acid by testing a series of indexes before and after the interaction between chlorogenic acid and Escherichia coli, to clarify the antibacterial mechanism of chlorogenic acid on Escherichia coli. Finally, by comparing the antibacterial activities of isochlorogenic acid A on Escherichia coli, it was concluded that both chlorogenic acid and isochlorogenic acid A showed antibacterial activities against Escherichia coli, wherein chlorogenic acid had a better antibacterial effect on Escherichia coli than isochlorogenic acid A.

Ruscogenin suppresses mouse neutrophil activation: Involvement of protein kinase A pathway.

Ruscogenin, a natural steroidal sapogenin, presents in both food and medicinal plants. It has been found to exert significant anti-inflammatory activities. Considering that activation of neutrophil is a key feature of inflammatory diseases, this study was performed to investigate the inhibitory effect of ruscogenin and its underlying mechanisms responsible for neutrophil activation. Ruscogenin displayed potent antioxidative effects against Formyl-Met-Leu-Phe (FMLP)-induced extra- and intracellular superoxide generation in mouse bone marrow neutrophils, with IC50 values of 1.07±0.32 µM and 1.77±0.46 µM, respectively. Phorbol myristate acetate (PMA)-elicited extra- and intracellular superoxide generation were also suppressed by ruscogenin, with IC50 values of 1.56±0.46 µM and 1.29±0.49 µM, respectively. However, ruscogenin showed weak inhibition in NaF-induced response. Inhibition of superoxide generation was mediated neither by a superoxide-scavenging ability nor by a cytotoxic effect. Furthermore, ruscogenin inhibited the membrane translocation of p47phox and p67phox. It reduced FMLP-induced phosphorylation of cytosolic phospholipase A2 (cPLA2) and p21-activated kinase (PAK). The cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were increased by ruscogenin. Moreover, ruscogenin inhibited phosphorylation of protein kinase B (Akt), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK). In addition, the inhibitory effects of ruscogenin on superoxide production and the phosphorylation of Akt, p38MAPK, and ERK1/2 were reversed by PKA inhibitor (H89), suggesting a PKA-dependent mechanism. In summary, our data suggest that ruscogenin inhibits activation of neutrophil through cPLA2, PAK, Akt, MAPKs, cAMP, and PKA signaling pathways. Increased PKA activity is associated with suppression of the phosphorylation of Akt, p38MAPK, and ERK1/2 pathways.

Diosgenin inhibits superoxide generation in FMLP-activated mouse neutrophils via multiple pathways.

Diosgenin possesses anti-inflammatory and anticancer properties. Activated neutrophils produce high concentrations of the superoxide anion which is involved in the pathophysiology of inflammation-related diseases and cancer. In the present study, the inhibitory effect and possible mechanisms of diosgenin on superoxide generation were investigated in mouse bone marrow neutrophils. Diosgenin potently and concentration-dependently inhibited the extracellular and intracellular superoxide anion generation in Formyl-Met-Leu-Phe (FMLP)- activated neutrophils, with IC50 values of 0.50 ± 0.08 µM and 0.66 ± 0.13 µM, respectively. Such inhibition was not mediated by scavenging the superoxide anion or by a cytotoxic effect. Diosgenin inhibited the phosphorylation of p47phox and membrane translocation of p47phox and p67phox, and thus blocking the assembly of nicotinamide adenine dinucleotide phosphate oxidase. Moreover, cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were also effectively increased by diosgenin. It attenuated FMLP-induced increase of phosphorylation of cytosolic phospholipase A (cPLA2), p21-activated kinase (PAK), Akt, p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK). Our data indicate that diosgenin exhibits inhibitory effects on superoxide anion production through the blockade of cAMP, PKA, cPLA2, PAK, Akt and MAPKs signaling pathways. The results may explain the clinical implications of diosgenin in the treatment of inflammation-related disorders.

Expression profile of insulin-like growth factor system genes in muscle tissues during the postnatal development growth stage in ducks.

Insulin-like growth factors (IGFs) are regulators that modulate the proliferation and differentiation of muscle tissues. We quantified the messenger RNA (mRNA) expression of IGF-I, IGF-II, and type I and II IGF receptors (IGF-IR and IGF-IIR) in muscle tissues including the breast, leg, and myocardium during an early postnatal development growth stage (post-hatching weeks 1-8) in ducks. The results showed a significant age-related change in mRNA in these muscle tissues. In breast muscle, the developmental expression of IGF-I and IGF-II was highest during week 1 but decreased quickly and maintained a relatively lower level. Leg muscle had the highest mRNA expression of IGF-I and IGF-II genes at week 3. In myocardial tissues, the expression level of IGF-IR and IGF-IIR genes exhibited a "rise-decline" developmental trend. The expression patterns of IGF-I/IGF-IR and IGF-II/IGF-IIR were different between weeks 4 and 6. The same expression pattern was observed for IGF-I and IGF-IR; however, it was different from that observed for IGF-II and IGF-IIR. Our results showed a negative correlation between IGF-II mRNA expression and leg muscle weight at week 4 (P < 0.05). A negative correlation was also found between IGF-II mRNA expression and breast muscle weight (P < 0.01), and a positive correlation was found between IGF-IR expression and breast muscle weight. At week 6, a positive correlation was found between IGF-IR expression and breast muscle weight. However, at week 8, a negative correlation was found between IGF-IR expression and breast muscle weight. The results showed that the expression of IGF mRNA in duck tissues exhibits a specific developmental trend and an age-related pattern, suggesting that the regulation mechanism of these 4 genes in proliferation and differentiation of muscle tissues differed.

Opposite effects of genistein on the regulation of insulin-mediated glucose homeostasis in adipose tissue.

BACKGROUND AND PURPOSE: Genistein is an isoflavone phytoestrogen found in a number of plants such as soybeans and there is accumulating evidence that it has beneficial effects on the regulation of glucose homeostasis. In this study we evaluated the effect of genistein on glucose homeostasis and its underlying mechanisms in normal and insulin-resistant conditions. EXPERIMENTAL APPROACH: To induce insulin resistance, mice or differentiated 3T3-L1 adipocytes were treated with macrophage-derived conditioned medium. A glucose tolerance test was used to investigate the effect of genistein. Insulin signalling activation, glucose transporter-4 (GLUT4) translocation and AMP-activated PK (AMPK) activation were detected by Western blot analysis or elisa. KEY RESULTS: Genistein impaired glucose tolerance and attenuated insulin sensitivity in normal mice by inhibiting the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1) at tyrosine residues, leading to inhibition of insulin-mediated GLUT4 translocation in adipocytes. Mac-CM, an inflammatory stimulus induced glucose intolerance accompanied by impaired insulin sensitivity; genistein reversed these changes by restoring the disturbed IRS1 function, leading to an improvement in GLUT4 translocation. In addition, genistein increased AMPK activity under both normal and inflammatory conditions; this was shown to contribute to the anti-inflammatory effect of genistein, which leads to an improvement in insulin signalling and the amelioration of insulin resistance. CONCLUSION AND IMPLICATIONS: Genistein showed opposite effects on insulin sensitivity under normal and inflammatory conditions in adipose tissue and this action was derived from its negative or positive regulation of IRS1 function. Its up-regulation of AMPK activity contributes to the inhibition of inflammation implicated in insulin resistance.