[Research progress of oral allergy syndrome].

Oral allergy syndrome (OAS) is an IgE-mediated hypersensitivity. Patients with pollen allergy will experience oropharyngeal allergy after eating fresh fruits or vegetables containing homologous pathogenesis-related allergen, occasionally accompanied by systemic symptoms, it is a special type of food hypersensitivity in which respiratory allergens and food allergens are similar structurally and lead to the cross-reactivity. At present, there is little research and attention to it in China. To master the definition, epidemiological characteristics, pathological mechanism, diagnosis, prevention and treatment of OAS is very important to the prevention and control of OAS. This article reviews the research progress of OAS, providing reference and prevention basis for clinicians to improve the diagnosis and differential diagnosis of OAS.

Interventional treatments for prolapsing haemorrhoids: network meta-analysis.

BACKGROUND: Multiple treatments for early-moderate grade symptomatic haemorrhoids currently exist, each associated with their respective efficacy, complications, and risks. The aim of this study was to compare the relative clinical outcomes and effectiveness of interventional treatments for grade II-III haemorrhoids. METHODS: A systematic review was conducted according to PRISMA criteria for all the RCTs published between 1980 and 2020; manuscripts were identified using the MEDLINE, Embase, and CENTRAL databases. Inclusion criteria were RCTs comparing procedural interventions for grade II-III haemorrhoids. Primary outcomes of interest were: symptom recurrence at a minimum follow-up of 6 weeks, postprocedural pain measured on a visual analogue scale (VAS) on day 1, and postprocedural complications (bleeding, urinary retention, and bowel incontinence). After bias assessment and heterogeneity analysis, a Bayesian network meta-analysis was performed. RESULTS: Seventy-nine RCTs were identified, including 9232 patients. Fourteen different treatments were analysed in the network meta-analysis. Overall, there were 59 RCTs (73 per cent) judged as being at high risk of bias, and the greatest risk was in the domain measurement of outcome. Variable amounts of heterogeneity were detected in direct treatment comparisons, in particular for symptom recurrence and postprocedural pain. Recurrence of haemorrhoidal symptoms was reported by 54 studies, involving 7026 patients and 14 treatments. Closed haemorrhoidectomy had the lowest recurrence risk, followed by open haemorrhoidectomy, suture ligation with mucopexy, stapled haemorrhoidopexy, and Doppler-guided haemorrhoid artery ligation (DG-HAL) with mucopexy. Pain was reported in 34 studies involving 3812 patients and 11 treatments. Direct current electrotherapy, DG-HAL with mucopexy, and infrared coagulation yielded the lowest pain scores. Postprocedural bleeding was recorded in 46 studies involving 5696 patients and 14 treatments. Open haemorrhoidectomy had the greatest risk of postprocedural bleeding, followed by stapled haemorrhoidopexy and closed haemorrhoidectomy. Urinary retention was reported in 30 studies comparing 10 treatments involving 3116 participants. Open haemorrhoidectomy and stapled haemorrhoidopexy had significantly higher odds of urinary retention than rubber band ligation and DG-HAL with mucopexy. Nine studies reported bowel incontinence comparing five treatments involving 1269 participants. Open haemorrhoidectomy and stapled haemorrhoidopexy had the highest probability of bowel incontinence. CONCLUSION: Open and closed haemorrhoidectomy, and stapled haemorrhoidopexy were associated with worse pain, and more postprocedural bleeding, urinary retention, and bowel incontinence, but had the lowest rates of symptom recurrence. The risks and benefits of each treatment should be discussed with patients before a decision is made.

[Berberine protects myocardial injury and cardiac dysfunction in a septic rat model].

Objectives: To investigated whether berberine could ameliorate septic cardiomyopathy in a rat model of sepsis and it's mechanisms. Methods: SD rats were divided into 3 groups: sepsis group (LPS group), rats were intraperitoneal injected of LPS (10 mg/kg); Berberine intervention group (Ber group), Ber (50 mg/kg, one time per day) was gavage fed 3 days before intraperitoneally injection of lipopolysaccharides (LPS); control group (Con group), rats were gavage fed with double distilled water (2 ml/100 g, one time per day) 3 days before intraperitoneal injection of normal saline (1 ml/100 g). LPS group and the Ber group was further divided into 3 subgroups (n=6), and the follow-up experiments were conducted at 6 h, 24 h and 48 h after LPS injection (of which 48 h subgroup rats were gavage fed with Ber/saline at 24 h). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of change of left ventricular pressure (±dp/dtmax) were monitored, the level of cardiac troponin T (cTnT), tumor necrosis factor (TNF)-α and interleukin (IL)-1ß was detected by ELISA method, HE staining of myocardial tissues was done to observe myocardial injury; Western blotting method was used to detect the expression of toll-like receptor 4(TLR4) protein in rat myocardial tissue, the level of myocardial cell nucleus protein p65 was detected to reflects the degree of NF-κB activation. The correlation of factors was analyzed with Pearson correlation analysis. Results: Pre-treatment with berberine stabilized cardiac hemodynamics and improved the systolic function and diastolic function in the heart of LPS-induced rats, as evidenced by the partial recovery of the reduced±dp/dtmax and LVSP, as well as the decreased LVEDP. Compared with the LPS group, the Ber group showed improved myocardial injury, as demonstrated by decreased cTnT at each time point. HE staining results showed that berberine decreased inflammatory cell infiltration and LPS-induced cell swelling. These effects were observed early at 6 hours, severe at 24 hours, and become more serious at 48 hours after LPS injection. Further, TLR4 and NF-κB p65 subunits, which were the two key factors of the TLR4/NF-κB signaling, were upregulated in the LPS group and attenuated in the Ber group. Consistently, the expression levels of the downstream cytokines TNF-α and IL-1ß were lower in the Ber group than those in the LPS group (all P<0.05). Myocardial injury markers were positively correlated with the markers of TLR4/NF-κB signals and the downstream host inflammatory factors (all P<0.05). Conclusions: Berberine can improve myocardial injury and cardiac function in sepsis rats, the mechanism is considered to be related to that it can inhibit the activation of TLR4/NF-κB signaling pathway induced by LPS and further reducing the production of TNF-α and IL-1ß.

The neuroprotection effect of oxygen therapy: A systematic review and meta-analysis.

This study reviews the oxygen therapy (normobaric oxygen [NBO] and hyperbaric oxygen [HBO]) in both stroke and traumatic brain injury (TBI) patients and meta-analyzes the efficacy of two oxygen therapies in different kinds of injuries. In stroke patients, NBO showed significant improvement in reperfusion rate while there is no favorable outcome effect of HBO treatment. In patients with TBI, HBO showed significant improvement of Glasgow outcome scale score and reduction of overall mortality while NBO may play a favorable role in improving brain metabolism.

[Effects of early enteral nutrition in the treatment of patients with severe burns].

Objective: To investigate the effects of early enteral nutrition (EEN) in the treatment of patients with severe burns. Methods: Medical records of 52 patients with severe burns hospitalized in the three affiliations of authors from August to September in 2014 were retrospectively analyzed and divided into EEN group (n=28) and non-early enteral nutrition (NEEN) group (n=24) according to the initiation time of enteral nutrition. On the basis of routine treatment, enteral nutrition was given to patients in group EEN within post injury day (POD) 3, while enteral nutrition was given to patients in group NEEN after POD 3. The following items were compared between patients of the two groups, such as the ratio of enteral nutrition intake to total energy intake, the ratio of parenteral nutrition intake to total energy intake, the ratio of total energy intake to energy target on POD 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28, the levels of prealbumin, serum creatinine, blood urea nitrogen, total bilirubin, direct bilirubin, and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score on POD 1, 3, 7, 14, and 28, the first operation time, the number of operations, and the frequencies of abdominal distension, diarrhea, vomiting, aspiration, catheter blockage, and low blood sugar within POD 28. Data were processed with χ(2)test, ttest, Wilcoxon rank sum test, and Bonferroni correction. Results: (1) The ratio of parenteral nutrition intake to total energy intake of patients in group EEN on POD 1 was obviously lower than that in group NEEN (Z=2.078, P<0.05). The ratio of enteral nutrition intake to total energy intake and the ratio of total energy intake to energy target of patients in group EEN on POD 2 and 3 were obviously higher than those in group NEEN (Z=5.766, 6.404, t=4.907, 6.378, P<0.01). The ratio of total energy intake to energy target of patients in group EEN was obviously lower than that in group NEEN on POD 4, 5, 6, and 7 (t=4.635, 2.547, 3.751, 5.373, P<0.05 or P<0.01). On POD 2, 4, 5, 14, 21, and 28, the ratio of enteral nutrition intake to total energy intake of patients in group EEN was obviously higher than the ratio of parenteral nutrition intake to total energy intake within the same group (Z=5.326, 2.046, 2.129, 4.118, 3.174, 3.963, P<0.05 or P<0.01). In group NEEN, the ratio of enteral nutrition to total energy intake of patients on POD 1, 2, and 3 was obviously lower than the ratio of parenteral nutrition intake to total energy intake within the same group (Z=2.591, 2.591, 3.293, P<0.05 or P<0.01), while the ratio of enteral nutrition to total energy intake of patients on POD 14, 21, 28 was obviously higher than the ratio of parenteral nutrition intake to total energy intake within the same group (Z=2.529, 3.173, 3.133, P<0.05 or P<0.01). (2) The prealbumin levels of patients in the two groups were close on POD 1, 3, 7, and 14 (t=1.983, 0.093, 0.832, 1.475, P>0.05). On POD 28, the prealbumin level of patients in group EEN was obviously higher than that in group NEEN (t=3.163, P<0.05). The levels of serum creatinine, blood urea nitrogen, total bilirubin, and direct bilirubin of patients in the two groups at all time points post injury were close (Z=1.340, 0.547, 0.245, 0.387, 0.009, 1.170, 0.340, 1.491, 0.274, 1.953, 0.527, 0.789, 0.474, 1.156, 0.482, 0.268, 0.190, 0.116, 1.194, 0.431, P>0.05). (3) The APACHE Ⅱ scores of patients in group EEN were (22.5±3.1) and (15.6±3.8) points respectively on POD 1 and 3, which were close to (23.6±3.0) and (17.6±4.2) points of patients in group NEEN (t=1.352, 1.733, P>0.05). The APACHE Ⅱ scores of patients in group EEN on POD 7, 14, and 28 were (13.6±3.6), (13.8±4.1), and (15.5±4.1) points, respectively, which were obviously lower than (18.5±3.9), (19.5±4.2) and (20.8±3.8) points of patients in group NEEN (t=4.677, 4.843, 4.792, P<0.05). (4) Within POD 28, the time of the first operation, the number of operations, and the frequencies of abdominal distension, diarrhea, vomiting, aspiration, catheter blockage and hypoglycemia were similar between patients of the two groups (t=0.684, 0.782, Z=0.161, 1.751, 0.525, 0.764, 0.190, 0.199, P>0.05). Conclusions: EEN in the treatment of patients with severe burns potentially increases the energy intake at early stage and improves APACHE Ⅱ score and prealbumin level on POD 28, without increasing frequencies of adverse reactions.

Identification of a 62-kDa major allergen from Artemisia pollen as a putative galactose oxidase.

BACKGROUND: Around 20 years ago, a 60- to 70-kDa protein was reported as a major allergen of mugwort (Artemisia vulgaris) pollen. This study was to identify and characterize its molecular properties. METHODS: Sera from 113 Chinese and 20 Dutch Artemisia-allergic/sensitized subjects (and pools thereof) were used to identify the 60- to 70-kDa allergen. Pollen extracts of seven Artemisia species were compared by immunoblotting. Transcriptomics and proteomics (mass spectrometry) of A. annua pollen were used to identify the putative 60- to 70-kDa Artemisia allergen. Both the natural purified and recombinant allergens were evaluated for IgE reactivity by ImmunoCAP. Fourteen Chinese Artemisia-allergic patients were tested intradermally with purified natural allergen. RESULTS: Immunoblots revealed two major bands at 12 and 25 kDa, and a weak band at 70 kDa for all seven Artemisia species. Using a combined transcriptomic and proteomic approach, the high molecular mass allergen in A. annua pollen was shown to be a 62-kDa putative galactose oxidase, with a putative N-glycosylation site. More than 94% of Artemisia pollen-allergic patients had IgE response to this allergen. Although recognition of a nonglycosylated recombinant version was only confirmed in a minority (16%) and at much lower IgE levels, this discrepancy cannot be explained simply by reactivity to the carbohydrate moiety on the natural allergen. Intradermal testing with the natural allergen was positive in five of nine sensitized patients. CONCLUSIONS: The previously reported 60- to 70-kDa allergen of Artemisia pollen is most likely a 62-kDa putative galactose oxidase here designated Art an 7.

Effects of Chinese herbal medicine and cold exposure on plasma glucose, leucine and energy metabolism in sheep.

An experiment was carried out to assess the feeding effect of Chinese herbal medicine on N balance, ruminal fermentation characteristics, kinetics of plasma glucose, leucine and energy metabolism in sheep kept at thermoneutral environment (23°C) or exposed to cold (2-4°C). Four sheep were subjected to either mixed hay (MH-diet) or hay supplemented with 2% of a traditional nourishing Chinese herbal medicine mixture (Astragalus root, Angelica root and Atractylodes rhizome; CHM-diet) over two 23-day periods using a crossover design. Cold exposure was conducted for 5 days. The isotope dilution of [U-13 C]glucose with open circuit calorimetry was used to determine the turnover and oxidation rates of plasma glucose and metabolic heat production. The rate of plasma leucine turnover was measured with an isotope dilution method using [1-13 C]leucine. N intake was higher, N excretion through faeces was lower and N digestibility was higher for the CHM-diet than the MH-diet. Rumen pH was lower, concentration of rumen NH3 was higher, concentrations of rumen total VFA and acetate tended to be higher and propionate was higher for the CHM-diet compared with the MH-diet. Turnover rate of plasma glucose was higher for the CHM-diet than the MH-diet and increased during cold exposure. Oxidation rate of plasma glucose did not differ between diets and also between environments. Turnover rate of plasma leucine was higher for the CHM-diet compared with the MH-diet but remained similar between environments. Heat production was greater for the CHM-diet than the MH-diet and increased during cold exposure. No significant diet × environment interaction was detected. The present results demonstrated that plasma glucose and energy metabolism were enhanced by both Chinese herbal medicine and cold exposure; plasma leucine metabolism was enhanced by Chinese herbal medicine but with lack of change in response to cold exposure in sheep under the conditions of the current experiment.

[Recurrent syncope related to catecholaminergic polymorphic ventricular tachycardia due to de novo RyR2-R2401H mutation].

Objective: To explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods: Clinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy. Results: Recurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation (R2401H) was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate (118.75 mg/d) was effective and patient was free of syncopal attack during the 2 years follow-up. Conclusion: This is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.

[Diagnosis and treatment of T1a-T1b prostate cancer].

OBJECTIVE: To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of incidental (stage T1a-T1b) prostate cancer. METHODS: Seven hundred and seventy-one patients who underwent TURP from May 2004 to September 2013 were analyzed retrospectively. In our institution, TURP specimens should be totally submitted in an extensive sampling method. The tumor area was outlined by estimation of an experienced genitourinary pathologist and calculated by the image analysis system software (Image J 1.47 h). The tumor area was then multiplied by the thickness of tissue. The total sum of all tumor volume was the estimated tumor volume. The clinical and pathological factors, follow-up results were obtained and we aimed to collect information about the period of watchful waiting (WW), PSA progression status, intervention status during the follow-up, the reason for intervention on WW and the type of intervention. RESULTS: The average age of 771 patients was (71.3±5.9) years old, and the average BMI was (23.9±3.1) kg/m2, preoperative average tPSA was (4.4±2.8) µg/L. Eighty-six (11.2%) cases of incidental prostate cancer were detected. The patients in T1a group (77 cases, 89.5%) had tumor volumes of (12.3±12.6) mm3, and the patients in T1b group had tumor volumes of (105.1±41.8) mm3.The range of tumor volume was 0.4-180.2 mm3. The volume of all the 86 cases was less than 500 mm3 as the threshold of insignificant cancer. All the patients were managed by WW. The mean follow-up time was 88.9 (27.9-150.1) months.The Gleason score was <7 in 79 patients, and ≥7 in 7 patients. There was no significant difference in age, preoperative tPSA, preoperative PSAD, postoperative tPSA, prostate volume and TURP resection between T1a group and T1b group (P>0.05). Among 84 patients without follow-up losts, PSA progression occurred in 5 patients. One T1a patient underwent radical prostatectomy (RP) as an intervention, and 3 patients underwent hormone therapy. One patient in T1b group underwent radiotherapy for PSA progression and one was treated because of patient preference without evidence of disease progression. There were no patients who died due to prostate cancer. CONCLUSION: Eighty-six (11.2%) cases of incidental prostate cancer were detected. The tumor volume of all the cases was insignificant cancer.The clinical outcomes of IPCa were satisfactory with the initial treatment of WW in the Chinese population.

Deletion of calponin 2 in macrophages attenuates the severity of inflammatory arthritis in mice.

Calponin is an actin cytoskeleton-associated protein that regulates motility-based cellular functions. Three isoforms of calponin are present in vertebrates, among which calponin 2 encoded by the Cnn2 gene is expressed in multiple types of cells, including blood cells from the myeloid lineage. Our previous studies demonstrated that macrophages from Cnn2 knockout (KO) mice exhibit increased migration and phagocytosis. Intrigued by an observation that monocytes and macrophages from patients with rheumatoid arthritis had increased calponin 2, we investigated anti-glucose-6-phosphate isomerase serum-induced arthritis in Cnn2-KO mice for the effect of calponin 2 deletion on the pathogenesis and pathology of inflammatory arthritis. The results showed that the development of arthritis was attenuated in systemic Cnn2-KO mice with significantly reduced inflammation and bone erosion than that in age- and stain background-matched C57BL/6 wild-type mice. In vitro differentiation of calponin 2-null mouse bone marrow cells produced fewer osteoclasts with decreased bone resorption. The attenuation of inflammatory arthritis was confirmed in conditional myeloid cell-specific Cnn2-KO mice. The increased phagocytotic activity of calponin 2-null macrophages may facilitate the clearance of autoimmune complexes and the resolution of inflammation, whereas the decreased substrate adhesion may reduce osteoclastogenesis and bone resorption. The data suggest that calponin 2 regulation of cytoskeleton function plays a novel role in the pathogenesis of inflammatory arthritis, implicating a potentially therapeutic target.

[Clinical features and prognostic analysis of high-risk acute promyelocytic leukemia patients].

OBJECTIVE: To investigate the clinical features and outcomes of high-risk acute promyelocytic leukemia (APL) patients. METHODS: A retrospective analysis was conducted to compare the clinical characteristics and prognosis of 118 high-risk APL patients (WBC≥10 × 10(9)/L) and 234 low and intermedia-risk patients (WBC <10×10(9)/L) from January 2003 to April 2015, who were treated in the First Affiliated Hospital of Zhejiang University and Yinzhou People's Hospital affiliated to Medical College of Ningbo University. RESULTS: The initial platelet counts of high-risk APL were significantly lower than that of low and intermediate-risk groups (P=0.003); the major type of PML-RARα isoforms in high-risk patients was short-form (51.8% vs 28.2%, P <0.001); the early death (ED) rate of high-risk patients was higher than low and intermedia-risk patients (20.3% vs 2.6%, P<0.001); in contrast, the complete remission (CR) rate and 5 years estimated overall survival (OS) rate of the former were lower than the latter (76.3% vs 94.9%, P <0.001; 74.2% vs 93.7%, P <0.001). However, the CR rate (P=0.682) and 5 years estimated OS rate (P=0.481) did not have difference when the ED patients were excluded. The 5 years estimated relapse-free survival (RFS) and central nervous system (CNS) relapse were 82.7%, 9.4%, respectively, which were lower than low and intermediate-risk groups (87.8%, 1.4% ) with statistic difference (P=0.048, 0.002). High-dose cytarabine and intrathecal chemotherapy may reduce the risk of CNS relapse. CONCLUSION: The outcomes of high-risk APL patients were worse than low and intermediate-risk group owing to the high ED rate and CNS relapse, it was important to decrease the ED rate and emphasis the CNS prophylaxis for high-risk APL patients.

[Basal cell carcinoma of prostate: a report of three cases].

To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of basal cell carcinoma (BCC) of prostate. Three cases of BCC of prostate were reported and the relevant literature was reviewed to investigate the diagnosis and treatment of this disease. We analyzed three cases of prostatic BCC. Their ages were within a range of 57 to 83 years. One of them complained of hematuria and two complained of dysuria. All of them presented with prostatic hyperplasia. Two of them presented with high prostate specific antigen (PSA) and one with normal PSA. Case 1 had prostate cancer invasion of bladder, rectal fascia, with lymph node metastasis, bone metastasis and lung metastases. The patient received bladder resection+bilateral ureteral cutaneous ureterostomy+lymph node dissection on November 2, 2014 . Postoperative pathological diagnosis showed BCC. Reexamination of pelvic enhanced MRI in January 8, 2015 suggested pelvic recurrence. Abdominal enhanced CT showed multiple liver metastases and pancreatic metastasis on July 11, 2015. Prostate cancer specific death occurred in October 2015. Case 2 was diagnosed as BCC in prostate biopsy on March 27, 2015. Positron emission tomography and computed tomography (PET-CT) showed pulmonary metastasis and bone metastasis. Then the patient received chemotherapy, endocrine therapy and local radiation therapy. Reexamination of PET-CT on January 11, 2016 showed that the lung metastase tumors and bone metastase tumors were larger than before. Up to January 10, 2016, the patient was still alive. Postoperative pathological changes of transurethral resection of prostate (TURP) in case 3 showed BCC might be considered. The PET-CT suggested residual prostate cancer, which might be associated with bilateral pelvic lymph node metastasis. In April 20, 2016, the review of PET-CT showed pelvic huge irregular hybrid density shadow, about 14.5 cm×10.0 cm×12.9 cm in size, and tumor recurrence was considered. Then the patient received local radiation therapy. The patient survived in the followed upon January 10, 2016. BCC of prostate is a rare subtype. Due to the local infiltrative and distant metastatic potentiality, active management is preferred and a life-long follow-up is necessary.

Rumex acetosa L. induces vasorelaxation in rat aorta via activation of PI3-kinase/Akt- AND Ca(2+)-eNOS-NO signaling in endothelial cells.

Rumex acetosa L. (RA) (Polygonaceae) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China and the aerial parts of RA has a wide variety of pharmacological actions such as diuretic, anti-hypertensive, anti-oxidative, and anti-cancer effects. However, the mechanisms involved are to be defined. The purpose of the present study was to evaluate the vasorelaxant effect and define the mechanism of action of the ethanol extract of Rumex acetosa L. (ERA) in rat aorta. ERA was examined for its vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aorta and its acute effects on arterial blood pressure. In addition, the roles of the nitric oxide synthase (NOS)-nitric oxide (NO) signaling in the ERA-induced effects were tested in human umbilical vein endothelial cells (HUVECs). The phosphorylation levels of Akt and eNOS were assessed by Western blot analysis in the cultured HUVECs. ERA induced endothelium-dependent vasorelaxation. The ERA-induced vasorelaxation was abolished by L-NAME (an NOS inhibitor) or ODQ (a sGC inhibitor), but not by indomethacin. Inhibition of PI3-kinase/Akt signaling pathway markedly reduced the ERA-induced vasorelaxation. In HUVECs, ERA increased NO formation in a dose-dependent manner, which was inhibited by L-NAME and by removing extracellular Ca(2+). In addition, ERA promoted phosphorylation of Akt and eNOS, which was prevented by wortmannin and LY294002, indicating that ERA induces eNOS phosphorylation through the PI3-kinase/Akt pathway. Further, in anesthetized rats, intravenously administered ERA decreased arterial blood pressure in a dose-dependent manner through an activation of the NOS-NO system. In summary, the ERA- induced vasorelaxation was dependent on endothelial integrity and NO production, and was mediated by activation of both the endothelial PI3-kinase/Akt- and Ca(2+)-eNOS-NO signaling and muscular NO-sGC-cGMP signaling.

Rubi Fructus (Rubus coreanus) activates the expression of thermogenic genes in vivo and in vitro.

OBJECTIVE: To investigate the anti-obesity effect of Rubi Fructus (RF) extract using brown adipose tissue (BAT) and primary brown preadipocytes in vivo and in vitro. METHODS: Male C57BL/6 J mice (n=5 per group) were fed a high-fat diet (HFD) for 10 weeks with or without RF. Brown preadipocytes from the interscapular BAT of mice (age, post-natal days 1-3) were cultured with differentiation media (DM) including isobutylmethylxanthine, dexamethasone, T3, indomethacin and insulin with or without RF. RESULTS: In HFD-induced obese C57BL/6 J mice, long-term RF treatment significantly reduced weight gain as well as the weights of the white adipose tissue, liver and spleen. Serum levels of total cholesterol and low-density lipoprotein cholesterol were also reduced in the HFD group which received RF treatment. Furthermore, RF induced thermogenic-, adipogenic- and mitochondria-related gene expressions in BAT. In primary brown adipocytes, RF effectively stimulated the expressions of thermogenic- and mitochondria-related genes. In addition, to examine whether LIPIN1, a regulator of adipocyte differentiation, is regulated by RF, Lipin1 small interfering RNA (siRNA) and RF were pretreated in primary brown adipocytes. Pretreatment with Lipin1 siRNA and RF downregulated the DM-induced expression levels of thermogenic- and mitochondria-related genes. Moreover, RF markedly upregulated AMP-activated protein kinase. Our study shows that RF is capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes. CONCLUSIONS: This study demonstrates that RF prevents the development of obesity in mice fed with a HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes, which suggests that RF has potential as a therapeutic application for the treatment or prevention of obesity.

Chronopharmacology of analgesic effect and tolerance induced by six narcotic analgesics in mice.

Narcotic analgesics, especially morphine, exert significantly different effects depending on the time within one day. The objective of this study was to observe whether the dosing time of 6 narcotic analgesics in mice affected their efficacy, pain tolerance and recovery of tolerance. The chronopharmacology of these 6 narcotics was evaluated using a hot-plate model. Maximum possible effect (MPE) of morphine showed a significant 24 h rhythm, which was higher during the dark phase and lower during the light phase (P<0.05). Conversely, MPEs of fentanyl and bucinnazine groups during the light phase exceeded those during the dark phase (P<0.05). Pain tolerance developed after drug administration at 9:00 am or 9:00 pm for 5 days, of which bucinnazine produced lower tolerance at 9:00 am. After a 2-day washout period, the mice rapidly recovered from tolerance at 3:00 pm for 5-day morphine dosing at 9:00 pm, and for fentanyl dosing at 9:00 am. Not all narcotic analgesics displayed significant circadian variations, and the dosing time-dependent effects also depended on the types of narcotics. Therefore, the time of administration is crucial in clinical pain treatment. Chronotherapy may be more effective to relieve pain while reducing side effects.

The effect of horse simulator riding on visual analogue scale, body composition and trunk strength in the patients with chronic low back pain.

BACKGROUND: Chronic low back pain (CLBP) is one of the most common musculoskeletal disorders, and thus effective treatments are required. Recently, real horseback riding has been reported to be beneficial for the patients. However, it has some limitations, such as limited approaches and safety issues. OBJECTIVE: The purpose of this study was to investigate the effect of horse simulator riding on back pain, body composition and trunk strength in the patients with CLBP. PARTICIPANTS: Forty-seven men with CLBP (mean age 20.55 ± 1.38 years) were randomly divided into a control group (n = 23) and a horse simulator riding group (n = 24), and visual analogue scale (VAS), body composition and isokinetic trunk strength were measured after 8 weeks for which subjects in a horse simulator riding group had performed the horse simulator exercise (HSE). RESULTS: Horse simulator exercise significantly reduced pain scores of VAS and enhanced isokinetic torques of trunk at 30 and 90°/s. There were also significantly increased muscle mass and decreased fat mass in horse simulator riding group. CONCLUSION: It can be inferred that HSE may be helpful in relief of back pain and recovery of back function through developing trunk strength and balancing the ratio of trunk flexor/extensor muscles.

Current-modulated electrical stimulation as a treatment for peripheral nerve regeneration in diabetic rats.

PURPOSE: To study if electrical stimulation (ES) can be a useful tool to improve functional recovery after neuronal injury in the peripheral nervous system. METHODS: We studied the effects of 2 Hz of percutaneous ES at different intensities of 1, 10 and 20 mA on peripheral nerve regeneration in rats with diabetes induced by streptozotocin. Non-stimulated diabetic rats were used as the sham-controls. A10-mm gap was made in the rat sciatic nerve by suturing the stumps into silicone rubber tubes and stimulation was carried out every other day for 3 weeks starting 1 week after surgery. RESULTS: After 4 weeks of recovery, the diabetic rats showed that ES of 1 mA or above could increase the cutaneous blood flow in their ipsilateral hindpaw to the injury. ES of 10 mA could improve the amplitude and the area of evoked muscle action potentials with faster target muscle reinnervation. ES of 10 mA could also ameliorate the calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn ipsilateral to the injury and the number of macrophages in the diabetic distal sciatic nerve. The impaired growth and maturation of regenerating axons in diabetic rat could be improved by ES of 10 mA or above. CONCLUSIONS: All these results lead to the conclusion that ES of 10 mA or above might be necessary to improve regeneration after a dissect lesion of the sciatic nerve in the diabetic rat.

High-frequency electrical stimulation can be a complementary therapy to promote nerve regeneration in diabetic rats.

The purpose of this study was to evaluate whether 1 mA of percutaneous electrical stimulation (ES) at 0, 2, 20, or 200 Hz augments regeneration between the proximal and distal nerve stumps in streptozotocin diabetic rats. A10-mm gap was made in the diabetic rat sciatic nerve by suturing the stumps into silicone rubber tubes. Normal animals were used as the controls. Starting 1 week after transection, ES was applied between the cathode placed at the distal stump and the anode at the proximal stump every other day for 3 weeks. At 4 weeks after surgery, the normal controls and the groups receiving ES at 20, and 200 Hz had a higher success percentage of regeneration compared to the ES groups at 0 and 2 Hz. In addition, quantitative histology of the successfully regenerated nerves revealed that the groups receiving ES at a higher frequency, especially at 200 Hz, had a more mature structure with more myelinated fibers compared to those in the lower-frequency ES groups. Similarly, electrophysiology in the ES group at 200 Hz showed significantly shorter latency, larger amplitude, larger area of evoked muscle action potentials and faster conduction velocity compared to other groups. Immunohistochemical staining showed that ES at a higher frequency could significantly promote calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn and recruit a higher number of macrophages in the diabetic distal sciatic nerve. The macrophages were found that they could stimulate the secretion of nerve growth factor, platelet-derived growth factor, and transforming growth factor-ß in dissected sciatic nerve segments. The ES at a higher frequency could also increase cutaneous blood flow in the ipsilateral hindpaw to the injury. These results indicated that a high-frequency ES could be necessary to heal severed diabetic peripheral nerve with a long gap to be repaired.

L-carnitine protects against cyclosporine-induced pancreatic and renal injury in rats.

BACKGROUND: L-carnitine has protective effects against various types of injury. This study was designed to evaluate the beneficial effects of L-carnitine on pancreatic and renal injuries caused by cyclosporine (CsA). METHODS: Rats maintained on a low sodium diet were given vehicle (olive oil, 1 mL/kg/d), CsA (15 mg/kg/d), L-carnitine (50 or 200 mg/kg/d), or a combination of CsA and L-carnitine for 4 weeks. The impact of L-carnitine on pancreatic injury was assessed by blood glucose levels, plasma insulin concentrations, and hemoglobulin A1c (HbA1c). In addition, the protective effects of L-carnitine against CsA-induced kidney injury were evaluated in terms of renal function, histopathology (inflammatory cell influx and tubulointerstitial fibrosis), oxidative stress (8-hydroxy 2'-deoxyguanosine, 8-OHdG), transforming growth factor-betal (TGF-ß1), apoptosis (caspase-3), and autophagy (LC3-II). RESULTS: CsA treatment caused diabetes, renal dysfunction, tubulointerstitial inflammation (ED-1-positive cells), and fibrosis, which were accompanied by an increase in 8-OHdG production and upregulation of TGF-ß1, caspase-3, and LC3-II. Concomitant administration of L-carnitine increased plasma insulin concentrations, decreasing plasma glucose and HbA1c levels. In the kidney, L-carnitine induced dose-dependent improvement of renal function, inflammation, and fibrosis in parallel with suppression of the expression of TGF-ß1 and 8-OHdG. Furthermore, the administration of L-carnitine at a high dose inhibited the expression of caspase-3 and LC3-II. CONCLUSION: These findings suggest that L-carnitine has a protective effect against CsA-induced pancreatic and renal injuries.