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BACKGROUND Since December 2019, there have been many new cases of coronavirus pneumonia in Wuhan, Hubei Province, which has gradually spread throughout the country. AIM To explore our hospital’s innovative management system to ensure the efficient operation of fever clinics during the epidemic, since controlling the spread of disease is an important way to prevent and control the epidemic. METHODS In total, 200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups. RESULTS The fever clinic in our hospital operated smoothly, and infection with the novel coronavirus disease (COVID-19) has not been reported in our hospital. Additionally, we did not have any cases of missed diagnosis. The awareness regarding COVID-19 infection sources, transmission routes, early symptoms, and preventive measures was significantly higher in our fever clinic than in those of the pre-management group. CONCLUSION "An integrated system, three separate responsibilities" ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases, which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital, ultimately achieving the maximum effect of epidemic prevention and control.

Long noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.

This study aimed to evaluate the effects of seven stages (Lonicera caerulea berry juice, after enzymatic hydrolysis, sugar and acid adjustments, fermentation, deacidification, clarification and ageing) in the making of Lonicera caerulea berry wine on the anthocyanins and antioxidant capacity were studied. The total anthocyanin content was determined by the pH-differential method. The composition of anthocyanins was measured by HPLC-MS/MS. The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azinobis (3-ethylbenzothiazoline- 6-sulphonic acid) (ABTS), ferric reducing potential (FRAP), total antioxidant capacity and cupric ion reducing antioxidant capacity assays were used to measure the antioxidant activities. Eight anthocyanins namely, cyanidin-3-hexoside derivatives, cyanidin-3-acetylhexoside, cyanidin-3-glucoside, peonidin-3-rutinoside, peonidin-3,5-dihexoside, peonidin-3-glucoside, cyanidin-3,5-dihexoside and pelargonidin-3-glucoside were detected in Lonicera caerulea berry wine and in all samples taken from each of the brewing processes. Addition of pectinase significantly increased the anthocyanin content by 69.04% and the peak areas of the individual anthocyanins increased, except for peonidin-3,5-dihexoside and peonidin-3-rutinoside. Although the anthocyanin content decreased throughout the entire process, each sample showed good antioxidant capacity.

SuHeXiang (SHX) has been used to treat a wide range of diseases, including those related to the central nervous system. However, the effects of SHX on mood disorders are still elusive. This study aimed to investigate the effects of SHX essential oil on stress-induced depression of mice. In an acute stress-induced depression model, mice inhaled vehicle (1% Tween 80) for 10 min or 10% SHX for 10 or 30 min once daily for 12 continuous days. In the chronic mild stress (CMS)-induced depression model, mice were exposed to a 28-d CMS treatment. Tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and novelty suppressed feeding (NSF) test were conducted. In addition, serum levels of angiogenin (ANG), thrombopoietin (TPO), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by enzyme-linked immunosorbent assay (ELISA) assays. The results showed that in mice exposed to acute stress, repeated SHX inhalation exerted significant antidepressant and anxiolytic activities, and also reduced the serum levels of ANG, TPO, IL-6, and TNF-α. It also significantly reversed the depressive and anxiety-like behaviors, and reduced the serum levels of ANG and TPO in mice exposed to CMS. This is the first report to show that SHX inhalation could produce significant antidepressant and anxiolytic-like effects. These effects might be mediated by SHX ability to modulate the inflammatory response, and reduce dysfunction of vascular genesis and thrombosis. These results support further exploration for developing SHX inhalation as a novel therapeutic strategy for depression and stress-related disorders.

Aims Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension. Materials and methods Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16 weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40 weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot. Key findings Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16 weeks) had greater benefits than short-term (6 weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression. Significance Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin–angiotensin–aldosterone system.

Objective The aim of this study was to evaluate the additional effects of acupuncture treatment on motor function in patients with subacute hemorrhagic stroke. Design One hundred and thirty-four patients with subacute hemorrhagic stroke were randomized to receive acupuncture treatment plus conventional treatment (treatment group) or conventional treatment only (control group). Acupuncture treatments were given in 24 sessions over 4 weeks, with 3-month follow-up period. Blinded evaluation was based on Fugl-Meyer Assessment, Barthel Index with an intention-to-treat analysis. For those patients who were able to walk, a three-dimensional gait analysis system was employed to objectively record spatiotemporal and kinematic parameters. Results Compared with control group, the treatment group showed a significantly greater over-time improvement in total Fugl-Meyer, lower-limb Fugl-Meyer, but not in upper-limb Fugl-Meyer and Barthel Index. The spatiotemporal parameters of velocity, step length, cadence, step width all showed significant difference between the 2 groups. The velocity in treatment group decreased unexpectedly at day 14, then increased sharply and overcame control group at day 28. The treatment group also showed a significantly greater increase in peak circumduction, peak hip hiking, hip range of motion, knee range of motion and a tendency for the ankle range of motion. Conclusions Acupuncture may promote the motor function recovery of hemorrhagic stroke patients in subacute phase mainly by enhancing the lower limb ability. It probably diminishes the compensation strategies earlier to correct the abnormal gait pattern. Although this adjustment may result in a compromise in the improvement of gait velocity temporarily, patients would benefit from it in a long run.

Background and Purpose: Lower limb spasticity is often a significant problem in stoke rehabilitation. The purpose of this study was to investigate the effects of acupuncture treatment on lower limb spasticity in patients following hemorrhagic stroke. Methods: Fifty-nine patients following hemorrhagic stroke were randomized to receive acupuncture treatment combined with conventional treatment (treatment group [TG]) or conventional treatment only (control group [CG]). Acupuncture treatments were given in 24 sessions over 4 weeks. Blinded evaluation was based on Modified Ashworth Scale (MAS), short intracortical inhibition (SICI), and Hmax/Mmax ratio as the primary outcomes. In addition, Fugl-Meyer Assessment (FMA), Barthel Index (BI), motor evoked potential (MEP) and surface integrated electromyogram (IEMG) were employed as the secondary outcomes. All the evaluations were performed at 14 and 28 days after the start of the treatment. Results: Compared with the CG, the TG showed a significantly greater over-time decrease in MAS for knee (p = 0.022) and ankle (p = 0.017), SICI (p = 0.000) and Hmax/Mmax ratio (p = 0.000). In all patients of TG, we found a greater improvement in lower-limb FMA and MEP but not in BI. IEMG show that TG obtained a greater reduction in spastic agonist muscles and a greater enhancement in spastic antagonist muscles. A significant correlation between a greater decrease in ankle MAS and a greater increase in SICI for spastic muscles was found (r = 0.390, p = 0.002). Conclusions: Acupuncture could improve the lower limb spasticity and motor function, thus providing a safe and economical approach for treating stroke patients. The potential mechanism underpinning the greater improvement may be attributed to a reshape of corticospinal plasticity induced by acupuncture.

Scott connection transformer can be used as traction transformer, which is an important part of electrified railway traction power supply system. The application of Scott connection transformer can solve current unbalance problem of three phase power source and realize bilateral power supply of the contact network. Scott transformer and back-to-back converter can be joined together to form the railway co-phase power supply system, which will not only provide the traction load with all needed active power, but also compensate negative sequence components, harmonics and reactive power. This provides a new idea for the development of traction power supply. A simulation with Matlab/Simulink is performed to validate the feasibility of this proposed control strategy.

The present study aimed to investigate the effect of Buyang Huanwu decoction (BYHWD) on tumor growth, metastasis and angiogenesis in nude mice bearing human hepatocellular carcinoma (HCC) HCCLM3 xenografts. A total of 96 nude mice bearing HCCLM3 xenografts were randomly divided into four groups: BYHWD group (LB), Yi‑qi decoction group (LY), Huo‑xue decoction group (LH) and model group (LM). Each of these groups was divided into three subgroups (n=8), which were observed on days 21, 25, 38 following treatment, respectively. The tumor weights, volumes and pulmonary metastases were recorded. The expression of CD105 and the microvessel density (MVD) were assessed, and the expression levels of vascular endothelial growth factor (VEGF), hypoxia‑inducible factor 1α (HIF‑1α), and regulator of G protein signaling 5 (RGS‑5) were analyzed using immunohistochemical staining. Compared with the LM group, no significant decrease in tumor weight or volume were observed in the herbal medicine treatment groups, the number of the metastases in the lungs decreased, whereas the expression levels of RGS‑5 and HIF‑1α decreased in the LB group on day 35. However, the expression levels of VEGF increased in the LB group on days 28 and 35 post‑treatment. The results of the present study suggested that BYHWD may inhibit angiogenesis and metastasis by affecting the expression levels of VEGF, RGS‑5 and HIF‑1α, and suggested that BYHWD may contribute to the tumor microenvironment and vasculature normalization in HCC.

Introduction The effects of edaravone against pentylenetetrazole (PTZ)‐induced epilepsy in male albino rats were investigated. Edaravone is a well‐known commercial drug used in the treatment of strokes and amyotrophic lateral sclerosis (ALS). Antioxidant and free radical scavenging activities of edaravone have been reported in patients with ALS. Methods In this study, the experimental groups were as follows: sham, control, 5 mg/kg edaravone, and 10 mg/kg edaravone. Behavioral assessment, determination of biochemical markers, apoptosis, nitric oxide (NO), and mRNA and protein expression of cyclooxygenase‐II (COX‐II) were carried out. Seizure incidence, including generalized tonic–clonic seizure (GTCS) and minimal clonic seizure (MCS), was directly associated with PTZ administration in rats. Results Edaravone supplementation substantially increased MCS and GTCS latency in rats, and biochemical markers were significantly altered in the brain tissue of PTZ‐treated rats. Edaravone treatment normalized altered biochemical markers compared with the untreated control. Apoptosis and NO levels were significantly reduced by more than 50% compared to their respective controls. COX‐II mRNA was increased by 130% in PTZ‐treated rats, while edaravone supplementation reduced mRNA and protein expression of COX‐II by more than 20% and 40%, respectively. Immunohistochemistry indicated that COX‐II protein expression was reduced by 13.2% and 33.7% following supplementation with 5 and 10 mg/kg edaravone, respectively. Conclusion Taken together, our results suggest that edaravone functions by downregulating the levels of COX‐II and NO and is a potential candidate for the treatment of PTZ‐induced epilepsy.

Oxidative stress plays an important role in the neuronal damage induced by epilepsy. The present study assessed the possible neuroprotective effects of astaxanthin (ATX) on neuronal damage, in hippocampal CA3 neurons following amygdala kindling. Male Sprague-Dawley rats were chronically kindled in the amygdala and ATX or equal volume of vehicle was given by intraperitoneally. Twenty-four hours after the last stimulation, the rats were sacrificed by decapitation. Histopathological changes and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and reduced glutathione (GSH) were measured, cytosolic cytochrome c (CytC) and caspase-3 activities in the hippocampus were also recorded. We found extensive neuronal damage in the CA3 region in the kindling group, which was preceded by increases of ROS level and MDA concentration and was followed by caspase-3 activation and an increase in cytosolic CytC. Treatment with ATX markedly attenuated the neuronal damage. In addition, ATX significantly decreased ROS and MDA concentrations and increased GSH levels. Moreover, ATX suppressed the translation of CytC release and caspase-3 activation in hippocampus. Together, these results suggest that ATX protects against neuronal loss due to epilepsy in the rat hippocampus by attenuating oxidative damage, lipid peroxidation and inhibiting the mitochondrion-related apoptotic pathway.

Brain oxidative stress due to chronic cerebral hypoperfusion was considered to be the major risk factor in the pathogenesis of vascular dementia. In this study, we investigated the protective efficacy of alpha-lipoic acid, an antioxidant, against vascular dementia in rats, as well as the potential mechanism. Bilateral common carotid arteries occlusion (BCCAO) induced severe cognitive deficits tested by Morris water maze (MWM), along with oxidative stress and disturbance of central cholinergic system. However, administration of alpha-lipoic acid (50mg/kg, i.p.) for 28 days significantly restored cognitive deficits induced by BCCAO. Biochemical determination revealed that alpha-lipoic acid markedly decreased the production of malondialdehyde (MDA) and the generation of reactive oxidative species (ROS), and increased the level of reduced glutathione (GSH) in the hippocampal tissue. Additionally, alpha-lipoic acid raised the level of acetylcholine (ACh) and choline acetyltransferase (ChAT) and decreased the activity of acetycholinesterase (AChE) in the hippocampus. These results indicated that treatment with alpha-lipoic acid significantly improved behavioral alterations, protected against oxidative stress, and restored central cholinergic system in the rat model of vascular dementia induced by BCCAO.

Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.

Prehypertension has been associated with adverse cerebrovascular events and brain damage. The aims of this study were to investigate i) whether short- and long-term treatments with losartan or amlodipine for prehypertension were able to prevent blood pressure (BP)-linked brain damage, and ii) whether there is a difference in the effectiveness of treatment with losartan and amlodipine in protecting BP-linked brain damage. In the present study, prehypertensive treatment with losartan and amlodipine (6 and 16 weeks treatment with each drug) was performed on 4-week-old stroke-prone spontaneously hypertensive rats (SHRSP). The results showed that long-term (16 weeks) treatment with losartan is the most effective in lowering systolic blood pressure in the long term (up to 40 weeks follow-up). Additionally, compared with the amlodipine treatment groups, the short- and long-term losartan treatments protected SHRSP from stroke and improved their brains structurally and functionally more effectively, with the long-term treatment having more benefits. Mechanistically, the short- and long-term treatments with losartan reduced the activity of the local renin-angiotensin-aldosterone system (RAAS) in a time-dependent manner and more effectively than their respective counterpart amlodipine treatment group mainly by decreasing AT1R levels and increasing AT2R levels in the cerebral cortex. By contrast, the amlodipine treatment groups inhibited brain cell apoptosis more effectively as compared with the losartan treatment groups mainly through the suppression of local oxidative stress. Taken together, the results suggest that long-term losartan treatment for prehypertension effectively protects SHRSP from stroke-induced brain damage, and this protection is associated with reduced local RAAS activity than with brain cell apoptosis. Thus, the AT1R receptor blocker losartan is a good candidate drug that may be used in the clinic for long-term treatment on prehypertensive populations in order to prevent BP-linked brain damage.

To investigate the effects of losartan and amlodipine on cell apoptosis in the cerebral cortex of stroke-prone spontaneously hypertensive rats (SHRSP) from the onset of prehypertension or hypertension. SHRSP were randomly divided into five experimental groups that were administered losartan, amlodipine (n=8 in each group; 4 weeks old or 10 weeks old), or vehicle, respectively. Wistar-Kyoto rats were used as control animals. Systolic blood pressure was measured using the tail-cuff method every 2 weeks. At 20 weeks of age, apoptosis was analyzed by TdT-mediated dUTP-biotin nick end labeling, and the level of angiotensin II was measured by radioimmunoassay. Protein expressions of gp91(phox), superoxide dismutase, and angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors in the cerebral cortex were detected by western blot. Losartan and amlodipine effectively delayed the progression of systolic blood pressure elevation, especially from the onset of prehypertension, and they had no obvious effects on the level of angiotensin II. In addition, treatment with losartan or amlodipine significantly decreased cell apoptosis, downregulated the protein expression of gp91(phox), and upregulated the protein expression of superoxide dismutase. The protein expressions of AT1R and AT2R were decreased by the administration of both drugs. No difference was found in the expression of AT1R among the drug treatment groups, whereas the expression of AT2R was increased in rats with increased blood pressure. Amlodipine, especially from the onset of prehypertension, was more effective than losartan in reducing apoptosis in the cerebral cortex in SHRSP. This may be related to the antioxidative stress properties of amlodipine.

Background/Purpose Effective stone disintegration by extracorporeal shockwave lithotripsy (ESWL) may depend on patient- and stone-related factors. We investigated predictors of disintegration failure in ESWL for a solitary ureteral calculus. Methods From July 2008 to May 2010, 203 patients who underwent ESWL for a solitary ureteral calculus were enrolled. Clinical and radiologic data were collected, and factors related to ESWL failure were analyzed. Results Fifty-two patients (25.6%) showed ESWL failure, with a mean follow-up of 41 days. Forty patients (19.7%) required retreatment, including 12 who underwent repeat ESWL and 28 who underwent curative ureteroscopy. Patients with ESWL failure had significantly higher body weight, body mass index (BMI), and buttock circumference (BC) than patients for whom ESWL was successful. Univariate analysis showed that stone burden (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03–1.06) and BC (OR, 1.06; 95% CI, 1.01–1.11) were predictors of ESWL failure, while BMI was a potential predictor with borderline significance (OR, 1.09; 95% CI, 0.99–1.20). Multivariate analysis showed that stone burden (OR, 1.04; 95% CI, 1.03–1.06) was a significant predictor for all patients. On stratifying patients according to the level of ureteral calculi, BC was found to be an independent predictor (OR, 1.35; 95% CI, 1.02–1.80) for ESWL failure for middle/lower ureteral calculi and BMI (OR, 1.47; 95% CI, 1.13–1.91) for upper ureteral calculi. Conclusion Stone burden is the main predictor of ESWL failure for all patients with ureteral calculi. BC and BMI are independent predictors for ESWL failure for middle/lower and upper ureteral calculi, respectively.

Statins are being widely used for the therapy and prevention of several types of tumors, including human chronic myelogenous leukemia, but the underlying molecular mechanisms still remain unknown. Therefore, inhibition of cell proliferation, apoptosis and involved molecules were investigated in K562 cells after incubation with simvastatin.The results showed that simvastatin diminished K562 cell proliferation and induced apoptosis. At the same time, the level of reactive oxygen species (ROS) and intracellular calcium concentration increased. Furthermore, nitric oxide (NO) content and inducible NO synthase (iNOS) mRNA expression were significantly higher in the simvastatin-treated group than in the corresponding control group. The elevated ROS level and intracellular calcium concentration, enhanced mRNA expression of iNOS and total NO content might be responsible for the apoptotic and anti-proliferative effects of simvastatin in K562 cells.

The current study investigated the efficacy of losartan and amlodipine in protecting spontaneously hypertensive stroke-prone (SHRSP) rats against the risk of stroke. SHRSP rats were administered losartan, amlodipine or the vehicle for 6 weeks. There were no significant differences in systolic blood pressure (SBP) in rats treated with losartan or amlodipine, however, following drug withdrawal, rats treated with losartan maintained reduced SBP for a longer time compared with rats treated with amlodipine. In addition, rats treated with losartan exhibited thinner vascular walls and improved systolic and diastolic function. Clinical stroke scores in the losartan group were significantly reduced compared with those in the amlodipine and vehicle groups. However, rats treated with losartan exhibited higher levels of angiotensin II and lower levels of aldosterone in the serum and brain cortex compared with the vehicle and amlodipine-treated rats. Furthermore, losartan significantly reduced the abnormal expression of angiotensin II receptors type 1 and 2 in SHRSP rats, whilst amlodipine did not. These results suggest that losartan may be more efficacious than amlodipine in ameliorating blood pressure deterioration and reducing stroke risk in SHRSP rats via regulation of the renin angiotensin system.

Oleoyl-chitosans (O-chitosans), with three degrees of substitution (DS), were synthesized by reacting chitosan with oleoyl chloride. The chemical structures of these polymers were characterized by 1H NMR and FTIR. The results suggested the formation of an amide linkage between amino groups of chitosan and carboxyl groups of oleic acid. These O-chitosans exhibited poor solubility in aqueous acidic solution. The solubility of O-chitosans decreased as the DS values increased. The transmittance of O-chitosans (2 g/L) with DS 5%, 11%, 27% in 1% (v/v) HCl solution were 69.5%, 62.7%, 48.6%, respectively. These O-chitosans were not soluble at neutral or alkali pH. Formation of self-aggregation was observed using pyrene as a fluorescent probe in the O-chitosans aqueous solution. The increase of DS of O-chitosans resulted in significant decrease of critical aggregation concentration (CAC). The CAC of the O-chitosans with DS 5%, 11%, 27% were 79.43, 31.6, 10 mg/L, respectively. The surface tension of solution could be reduced slightly by all of the O-chitosans. The surface tension of O-chitosans solution decreased with the increase of DS values. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:1968–1973, 2006

Resolvin D1 (7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) (RvD1), generated from ω-3 fatty docosahexaenoic acids, is believed to exert anti-inflammatory properties including inhibition of neutrophil activation and regulating inflammatory cytokines. In this study, we sought to investigate the effect of RvD1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. In vivo, RvD1 was injected i.v. (5 μg/kg) 8 h after LPS (20 mg/kg) administration, which markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema. In addition, rat lung tissue protein was isolated after intervention and we found RvD1 improved epithelial sodium channel (ENaC) α, γ, Na,K-adenosine triphosphatase (ATPase) α1, β1 subunit protein expression and Na,K-ATPase activity. In primary rat alveolar type II epithelial cells stimulated with LPS, RvD1 not only upregulated ENaC α, γ and Na,K-ATPase α1 subunits protein expression, but also increased Na+ currents and Na,K-ATPase activity. Finally, protein kinase A and cGMP were not responsible for RvD1’s function because a protein kinase A inhibitor (H89) and cGMP inhibitor (Rp-cGMP) did not reduce RvD1’s effects. However, the RvD1 receptor (formyl-peptide receptor type 2 [FPR2], also called ALX [the lipoxin A4 receptor]) inhibitor (BOC-2), cAMP inhibitor (Rp-cAMP), and PI3K inhibitor (LY294002) not only blocked RvD1’s effects on the expression of ENaC α in vitro, but also inhibited the AFC in vivo. In summary, RvD1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/cAMP/PI3K signaling pathway.

Involved with many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, GPCRs (G-protein-coupled receptors) are the most frequent targets for drug development: over 50% of all prescription drugs currently on the market are actually acting by targeting GPCRs directly or indirectly. Found in every living thing and nearly all cells, ion channels play crucial roles for many vital functions in life, such as heartbeat, sensory transduction, and central nervous system response. Their dysfunction may have significant impact to human health, and hence ion channels are deemed as "the next GPCRs". To develop GPCR-targeting or ion-channel-targeting drugs, the first important step is to identify the interactions between potential drug compounds with the two kinds of protein receptors in the cellular networking. In this minireview, we are to introduce two predictors. One is called iGPCR-Drug accessible at http://www.jci-bioinfo.cn/iGPCR-Drug/; the other called iCDI-PseFpt at http://www.jci-bioinfo.cn/iCDI-PseFpt. The former is for identifying the interactions of drug compounds with GPCRs; while the latter for that with ion channels. In both predictors, the drug compound was formulated by the two-dimensional molecular fingerprint, and the protein receptor by the pseudo amino acid composition generated with the grey model theory, while the operation engine was the fuzzy K-nearest neighbor algorithm. For the convenience of most experimental pharmaceutical and medical scientists, a step-bystep guide is provided on how to use each of the two web-servers to get the desired results without the need to follow the complicated mathematics involved originally for their establishment.

Fibroblasts, far frombeing merely bystander cells, are known to play a specific role in inflammation resolution after an acute injury. As the endogenous “braking signal,” resolvins possess potent anti-inflammatory and proresolution actions. We demonstrated that the expression of COX-2 protein was significantly peaked initially at 6 hours but then also at 48 hours after LPS stimulation in lung fibroblasts. PGE2levels also peaked at 6 hours, and PGD2levels were increased and peaked at 48 hours. However, no significant change in the protein expression of COX-1 was observed after treatment with LPS in lung fibroblasts. Exogenous resolvin D1 inhibited the first peak of COX-2 expression as well as the production of PGE2induced by LPS. In contrast, exogenous resolvin D1 increased the second peak of COX-2 expression as well as the production of PGD2induced by LPS. In addition, resolvin D1 inhibited COX-2 expression at 6 hours, which was partly through PI3K/AKT and ERK2 signalling pathways.

Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called "iGPCR-drug", was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug - target interaction networks.

Current approaches for treatment of late-stage breast cancer rarely result in a long-term cure. In part this is due to tumor stroma that prevents access of systemically or intratumorally applied therapeutics. We propose a stem cell gene therapy approach for controlled tumor stroma degradation that uses the pathophysiologic process of recruitment of inflammatory cells into the tumor. This approach involves genetic modification of hematopoietic stem cells (HSCs) and their subsequent transplantation into tumor-bearing mice. We show that inducible, intratumoral expression of relaxin (Rlx) either by transplanting tumor cells that contained the Rlx gene or by transplantation of mouse HSCs transduced with an Rlx-expressing lentivirus vector delays tumor growth in a mouse model of breast cancer. The antitumor effect of Rlx was mediated through degradation of tumor stroma, which provided increased access of infiltrating antitumor immune cells to their target tumor cells. Furthermore, we have shown in a human/mouse chimeric model that genetically modified HSCs expressing a transgene can access the tumor site. Our findings are relevant for cancer gene therapy and immunotherapy.

Background: Statins, a family of 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitors, are being investigated for the therapy and prevention of cancers. Here we aimed to investigate the effects of simvastatin on chronic myelogenous leukemia (CML) cells in vitro and in vivo, and to elucidate the mechanisms. Methods: Cell proliferation and cell cycle were measured after K562 cells were incubated with simvastatin, and differentially expressed genes were determined by oligonucleotide microarray. Changes of 2 genes obtained by oligonucleotide microarray were validated by real-time RT-PCR, and immunohistochemistry was performed to determine expression of proliferating cell nuclear antigen (PCNA). Finally, a xenograft tumor model was constructed to evaluate the effects of simvastatin in vivo. Results: Simvastatin could inhibit K562 cell proliferation, and the inhibition rate was approximately 30% after treatment with 20 µmol/l simvastatin for 48 h. Cell cycle was arrested in G1 phase, as shown by flow cytometry results. Fifteen downregulated, 9 upregulated cell cycle-related genes and decreased PCNA protein were observed in the presence of simvastatin. Furthermore, simvastatin exhibited impairment of xenograft tumor growth in nude mice and also blocked cell cycle in G1 phase. Conclusion: Simvastatin can inhibit CML cell proliferation in vitro and in vivo, and its mechanisms might be involved in cell cycle regulation.

A patient sustained high-voltage electrical burns with third-degree burns over 35.5% of his body surface, which included a large direct wound on the left chest wall, exposing the heart. The heart and lungs were severely injured. Subsequently, hydrothorax, hydropericardium, and respiratory failure developed. He was successfully treated with fluid resuscitation, antibiotics, drainage of the pericardium and pleural cavities, early removal of necrotic tissue, skin grafting, and reconstruction of the chest wall with a 13 x 27-cm delay-flap, as well as a number of supportive measures. The patient gradually recovered and was discharged in 6 months.

Objective To study the mechanism of herbal application along meridians for treatment and prevention of asthma by using serum pharmacological test to observe the effects of serum containing herbs against the constriction of tracheal spiral strips induced by acetylcholine chloride (Ach). Methods Guinea pigs were randomly divided into normal control group, normal saline (NS) application group, aminophylline application group, aminophylline injection group, 1-day herb application group, 7-day herb application group and 14-day herb application group. Asthma was induced by Hutson's method in guinea pigs except the normal control group. Guinea pigs in herb application groups were treated by external application of a compound herbal medicine 60 min once every day. Guinea pigs in NS application group were treated by external application of NS. Guinea pigs in the two aminophylline-treated groups were treated by external application and intraperitoneal injection of aminophylline at a dose of 400 mg/kg, respectively. The guinea pigs were killed and the sera were obtained after 1-day, 7-day and 14-day treatment in the three herb application groups, 7-day treatment in the NS application group, the aminophylline application and injection groups, respectively. Serum pharmacological method was used to do the experiment, the effects of different sera on the constriction of tracheal strips were observed, and the constriction rates were calculated. Result The serum containing herbs had an effect in reducing the constriction of tracheal spiral strips induced by Ach, and the effect was similar to that of the serum obtained from the aminophylline injection group. The constriction rate of the tracheal spiral strips was decreased when herbal application treatment was prolonged within a period of time, and it became stable when herbal application treatment was between 7-14 days. The constriction of tracheal spiral strips induced by Ach could be reduced remarkably when it was previously treated by serum containing herbs. Conclusion The anti-acetylcholine function with a time-dependent effect is one of the mechanisms of herbal application treatment along meridians for asthma, and furthermore, herbal application treatment along meridians might be useful for preventing asthma.

Ro 40-5967 is a structurally novel Ca 2+ channel blocker which binds to the [ 3 H]desmethoxyverapamil receptor in cardiac membranes with a potency similar to that of verapamil but which has considerably fewer negative inotropic effects. In the present study, the inward Ca 2+ current was measured in isolated myocytes with the whole-cell patch-clamp technique. It was found that at a physiological membrane potential ( − 80 mV) Ro 40-5967 was also less potent than verapamil in inhibiting this current, and that negative inotropy and Ca 2+ channel blockade were correlated.

The absorption spectra of Nd3+ in pure anhydrous neodymium chloride crystals and in anhydrous praseodymium chloride crystals (containing 0.1% NdCl3) have been examined systematically examined. The structures of the groups of their absorption lines are found to be similar to those of Nd3+ in NdCl3 crystals diluted by LaCl3 (containing 2% NaCl3 in LaCl3), except for a shift of the spectrum towards the long wave side. The shifts (relative to the ground state) of these corresponding sub-levels are proportional to the length of unit cell of the single crystals.