Nitroglycerin combined with NSAIDs for prevention of post-ERCP pancreatitis: A meta-analysis of prospective, randomized, controlled trials.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. OBJECTIVE: A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. METHODS: Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. RESULTS: A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. CONCLUSION: GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.

Stereoselective Synthesis of Polysubstituted Dihydropyrroles via 1,5-Addition and N-1,4-Addition Cascade.

An unprecedented 1,5-addition/N-1,4-addition cascade reaction is established via palladium hydride catalysis. A variety of polysubstituted dihydropyrrole skeletons are constructed in high yield and with exclusively >20 : 1 diastereoselectivity. An enantioselective protocol of this design is also developed to provide a novel access to enantioenriched dihydropyrroles.

Population Pharmacokinetics of Tigecycline: A Systematic Review.

Although tigecycline is widely used in clinical practice, its efficiency and optimal dosage regimens remain controversial. The purpose of this article was to help guide tigecycline dosing in different patient subpopulations through comparing the published population pharmacokinetic models of tigecycline, as well as summarizing and determining the potential covariates that markedly influence tigecycline pharmacokinetics. In this review, literature was systematically searched from the PubMed database from inception to March 2022. The articles focusing on population pharmacokinetics for tigecycline in healthy volunteers or patients were included; finally, a total of eight studies were included in this review. NONMEM methods were used in five studies to generate the population pharmacokinetic models. Tigecycline pharmacokinetics were mostly described by a two-compartment model in these included studies. Estimated clearance and volumes of distribution of tigecycline at steady state (Vss) varied widely in different target patient populations, with a range of 7.5-23.1 L/h and 212.7-1087.7 L, respectively. Body-weight and creatinine clearance were the most important predictors of clearance in these studies, while other predictors include age, gender, bilirubin and aspartate aminotransferase. In conclusion, this review showed the large variability of tigecycline population pharmacokinetics, which can provide guide dosing in different target populations. For clinicians, the individual dosing adjustment should be based not only on the indication and pathogen susceptibility but also on the potential important predictors. However, more studies were needed to confirm the necessity of modified dosage regimens in different patient subpopulations.

Inherently Area-Selective Atomic Layer Deposition of Manganese Oxide through Electronegativity-Induced Adsorption.

Manganese oxide (MnOx) shows great potential in the areas of nano-electronics, magnetic devices and so on. Since the characteristics of precise thickness control at the atomic level and self-align lateral patterning, area-selective deposition (ASD) of the MnOx films can be used in some key steps of nanomanufacturing. In this work, MnOx films are deposited on Pt, Cu and SiO2 substrates using Mn(EtCp)2 and H2O over a temperature range of 80-215 °C. Inherently area-selective atomic layer deposition (ALD) of MnOx is successfully achieved on metal/SiO2 patterns. The selectivity improves with increasing deposition temperature within the ALD window. Moreover, it is demonstrated that with the decrease of electronegativity differences between M (M = Si, Cu and Pt) and O, the chemisorption energy barrier decreases, which affects the initial nucleation rate. The inherent ASD aroused by the electronegativity differences shows a possible method for further development and prediction of ASD processes.

Metabolic syndrome emerges after artificial selection for low baroreflex sensitivity.

AIMS: It is unclear whether the impaired BRS plays a key role in the incidence of cardiovascular diseases. The molecular mechanism of impaired BRS remains to be fully elucidated. We hypothesized that selection of rats based on deficient and normal intrinsic BRS would yield models that reflect cardiovascular diseases risk. METHODS AND RESULTS: Twenty generations of selection produced arterial baroreflex low rats and normal rats that differed in BRS by about 2.5-fold change. Metabolic syndrome (including hypertension, overweight, hyperlipemia, and hyperglycemia) emerged in ABR-DRs. Although ABR-DRs consumed less food, they gained significantly more body weight. CONCLUSION: Our study demonstrated that intrinsic low BRS induced hypertension and metabolic disorder. Restoration of impaired BRS might be a potent target of therapeutic intervention in metabolic syndrome.

TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension.

Angiotensin II (Ang II)-induced injury of vascular smooth muscle cells (VSMCs) serves an important role in hypertension and other cardiovascular disorders. Transient receptor potential melastatin 8 (TRPM8) is a thermally­regulated Ca2+­permeable channel that is activated by reduced body temperature. Although several recent studies have revealed the regulatory effect of TRPM8 in vascular tone and hypertension, the precise role of TRPM8 in dysfunction of vascular smooth muscle cells (VSMCs) induced by Ang II remains elusive. In the present study, the possible function of TRPM8 in Ang II­induced VSMCs malfunction in vivo and in vitro was investigated. In the aortae from rats that had undergone a two­kidney one­clip operation, which is a widely­used renovascular hypertension model, the mRNA and protein levels of TRPM8 were reduced. In addition, exogenous Ang II treatment decreased TRPM8 mRNA and protein expression levels in primary cultures of rat VSMCs. TRPM8 activation by menthol, a pharmacological agonist, in VSMCs, significantly attenuated the Ang II­induced increase in reactive oxygen species and H2O2 production. In addition, TRPM8 activation reduced the Ang II­induced upregulation of NADPH oxidase (NOX) 1 and NOX4 in VSMCs. Furthermore, TRPM8 activation relieved the Ang II­induced activation of ras homolog gene family, member A­rho associated protein kinase 2 and janus kinase 2 signaling pathways in VSMCs. In conclusion, the results presented in the current study indicated that TRPM8 downregulation by Ang II in VSMCs may be involved in hypertension.

[Effect of miR-21 in promoting angiogenesis differentiation of umbilical cord blood mesenchymal stem cells in vitro].

PURPOSE: To investigate the effect of miR-21 on promoting vascular differentiation of umbilical cord blood derived mesenchymal stem cells (UCBMSCs) in vitro. METHODS: UCBMSCs (from Stem Cell Bank of Tongji University) were cultured; Lenti-LacZ-Luciferase and Lenti-miR-21-Luciferase Lentiviral vector were reconstructed; Real-time fluorescence quantification PCR and Western blot were performed to detect the expression of key angiogenic factors at 0, 1, 4, 7 and 14 d after target gene was transduced into UCBMSCs; UCBMSCs of the third generation were transduced with Lenti-LacZ-Luciferase and Lenti-miR-21- Luciferase; matrigel tube assay was performed to observe the tube-like structure under microscope. The data were statistically analyzed using Student's t test and variance analysis with SPSS13.0 software package. RESULTS: UCBMSCs were successfully cultured; The results of qPCR and Western blot showed the expression of HIF-1α and VEGF in miR-21 group significantly increased at 4 d and continued until 7 d and 14 d; Matrigel results showed the tubular structures in Lenti-miR-21-Luciferase group were more than other groups both in amount and in length. CONCLUSIONS: MiR-21 can promote vascular differentiation of UCBMSCs.

A combination of neostigmine and anisodamine protects against ischemic stroke by activating α7nAChR.

BACKGROUND: Increasing endogenous acetylcholine by neostigmine decreased the ischemic cerebral injury. The off-target action on muscarinic receptor produced a variety of adverse effects and limited the clinical application on stroke. AIM: We combined neostigmine with anisodamine and investigated the neuroprotection and mechanism. METHODS: Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Neuroprotective action of neostigmine in combination with anisodamine at varying ratios was examined to determine the optimal combination as well as ideal therapeutic window. Potential involvement of α7 nicotinic acetylcholine receptor was examined by measuring the infarct size, the expression of proinflammatory cytokines, and the biomarkers of apoptosis in α7 nicotinic acetylcholine receptor knockout mice. A set of in vitro experiments was conducted in RAW264.7 cells to probe into potential molecular mechanisms. RESULTS: The neostigmine/anisodamine combination conferred neuroprotection. The protection was most potent at a ratio of 1:500. At such a ratio, the combination increased the binding of acetylcholine to α7 nicotinic acetylcholine receptor and reduced proinflammatory cytokines. The neuroprotection was evident only in wild-type and not in α7 nicotinic acetylcholine receptor knockout mice. The combination significantly decreased the expression of Bad and Bax, and increased Bcl-2 and Bcl-xl in α7 nicotinic acetylcholine receptor wild-type mice but not in knockout mice. The combination did not affect caspase-8, cleaved caspase-8, or caspase-12. CONCLUSIONS: Current study identified the optimal combination of neostigmine and anisodamine against ischemic stroke, and indicated that the acetylcholine-α7 nicotinic acetylcholine receptor is involved in the protective effects.

An evaluation of Frankliniella occidentalis (Thysanoptera: Thripidae) and Frankliniella intonsa (Thysanoptera: Thripidae) performance on different plant leaves based on life history characteristics.

To compare the performance of Frankliniella occidentalis (Pergande) and native Frankliniella intonsa (Trybom) on cucumber and tomato leaves in laboratory, life history characters were investigated, and life tables were constructed using the method of age-stage, two-sex table life. Compared with tomato leaf, there were shorter total preoviposition period (TPOP), higher fecundity, longer female longevity, and higher intrinsic rate of increase (r) of both F. occidentalis and F. intonsa on cucumber leaf. Meanwhile, on cucumber leaf, the shorter TPOP, higher fecundity, longer female longevity, and higher value of r were found on population of F. intonsa but on tomato leaf which were found on population of F. occidentalis. From above, cucumber leaf was the preference to population development of both F. occidentalis and F. intonsa compared with tomato leaf. Nevertheless, on cucumber leaf, population of F. intonsa would grow faster than that of F. occidentalis, which was the opposite on tomato leaf. As to the population development in fields, much more factors would be taken into account, such as pollen, insecticide resistance, and effects of natural enemies etc.

The smallest spectral radius of graphs with a given clique number.

The first four smallest values of the spectral radius among all connected graphs with maximum clique size ω ≥ 2 are obtained.

On the signless laplacian spectral radius of bicyclic graphs with perfect matchings.

The graph with the largest signless Laplacian spectral radius among all bicyclic graphs with perfect matchings is determined.

Effects of combination therapy with levamlodipine and bisoprolol on stroke in rats.

AIM: To examine the effects of combination with levamlodipine and bisoprolol on stroke in rats. METHODS: For acute study, Systolic blood pressure (SBP) and heart period (HP) were monitored in conscious stroke prone-spontaneously hypertensive rats (SHR-SP) and sinoaortic denervation (SAD) rats before and after intragastric administration of either drug at a single dose. Rats were subjected to middle cerebral arterial occlusion (MCAO) half an hour after drug administration; sacrificed 24 h later to measure the infarct size. For long-term study, drugs (either alone or in combination) were delivered via food to SHR-SP. The survival time was recorded. RESULTS: SBP was significantly reduced by combination therapy both in SHR-SP and SAD rats. Neutralization on heart rate (HR) was observed in combination. The drug combination increased baroreflex sensitivity (BRS) and reduced SBP variability (SBPV). In chronic experiments, the lifespan of SHR-SP rats exposed to the drug combination was longer than that in rats exposed to either drug alone. The infarct area was the smallest in subjects receiving drug combination in SD rats both with and without SAD. CONCLUSION: Combined use of levamlodipine and bisoprolol produced better protection against stroke.

Reproduction of the solenopsis mealybug, Phenacoccus solenopsis: males play an important role.

The solenopsis mealybug, Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae), is an aggressive pest threatening crops worldwide. The biology of P. solenopsis has been described in several studies, but detailed information on the reproduction of P. solenopsis has not been investigated. The results of our study showed: 1) no progeny could be produced by virgins; 2) apoptosis of follicle cells, which occurs when the eggs begin to develop, did not happen in virgins; and 3) oosorption occurred in the unfertilized eggs. This suggests that P. solenopsis is an obligate amphimictic species, and resorption of developed eggs fits the "wait to reproduce" oosorption hypothesis. Compared to females that mated when they were two days old, the females that mated 30 days after eclosion had lower reproductive output and longer adult lifespans, but had higher reproductive output and shorter lifespan than those of the unmated females. Such a phenomenon suggests that resources obtained from eggs can be allocated for survival until conditions for reproduction improve. The results of this study provide evidence for a trade-off between survival and future reproduction: delayed reproductive conditions trigger physiological states geared toward survival at the expense of reproduction. The mating history of the males had no effect on progeny production.

Synergic effects of levamlodipine and bisoprolol on blood pressure reduction and organ protection in spontaneously hypertensive rats.

AIMS: Stroke is a major cause of disability and death worldwide. Hypertension is one of the most important risk factors for stroke. The objective of this work was to study the synergic effects of levamlodipine and bisoprolol on blood pressure reduction and organ protection in spontaneously hypertensive rats (SHR). METHODS: Blood pressure was continuously monitored in conscious SHR. For acute study, a single dose of drugs was administrated via an intragastric catheter. For chronic study (4 months), drugs were delivered via rat chow. RESULTS: A single dose of levamlodipine (from 1 mg/kg), bisoprolol (from 0.125 mg/kg), and their combinations significantly decreased blood pressure. The levamlodipine-induced tachycardia and the bisoprolol-induced bradycardia were temporized by the combination of these two drugs. Upon chronic treatment, this combination also decreased blood pressure variability and reduced organ damage. CONCLUSION: Levamlodipine and bisoprolol produce synergic effects on blood pressure reduction and organ protection in SHR.

[Therapeutic effect of 125I-103Pd hybrid radioactive seeds on pulmonary carcinomas in BALB/c-nu mice].

OBJECTIVE: To prepared (125)I-(103)Pd hybrid radioactive seeds and to explore their therapeutic effect on pulmonary carcinomas. METHODS: The (125)I-(103)Pd hybrid radioactive seeds were prepared by a chemical method of step-by-step coat plating. Pulmonary adenocarcinoma of GLC-82 cells and pulmonary large cell carcinoma of H460 cells were cultured in vitro and then were exposed directly to (125)I, (103)Pd and (125)I-(103)Pd seeds for 48 hours to observe the killing effects of radiation. GLC-82 and H460 tumor models were established and 20 mice chosen randomly for each model. For each tumor model, there were 4 groups (n = 5 each). Then (125)I-(103)Pd, (125)I, (103)Pd and nonradioactive seeds were implanted into the tumors. Tumor sizes and weights of mice were measured and recorded every 5 days for a 2-month observation. RESULTS: The (125)I-(103)Pd hybrid radioactive seeds were prepared successfully. After a 48-hour radiation from radioactive seeds, the GLC-82 cells within one particulate around (125)I, (103)Pd or (125)I-(103)Pd seeds were inhibited so as to become swollen and transfiguring. The H460 cells around (125)I seeds showed no obvious abnormality while those within one particulate around (103)Pd or (125)I-(103)Pd seeds were much fewer. No mouse died during the observation period. The radioactive seeds could inhibit the tumors. The radiotherapeutic effects were similar in two tumor modes: (125)I-(103)Pd seeds > (103)Pd seeds ≈ (125)I seeds > non-radioactive seeds. H460 tumors grew much faster than GLC-82 tumors. Meanwhile the seeds with the same nuclide were much more effective for GLC-82 tumors than for H460 tumors. CONCLUSION: The (125)I-(103)Pd hybrid radioactive seeds are clinically applicable due to their effective inhibitions of tumor growth.

[Expression of dopamine receptor D2 in pulmonary carcinoma cells and effects of dopamine on the cell apoptosis].

OBJECTIVE: To detect the expression of dopamine receptor D2 in different pulmonary carcinoma cells and investigate the effect of dopamine in inducing apoptosis of A549 cells. METHODS: Western blotting and RT-PCR were employed to detect the expression of dopamine receptor D2 in different pulmonary carcinoma cells (95D, H460, GLC-82, A549 and H446 cells). The apoptosis of A549 cells after a 6-hour exposure to 0.02%, 0.04%, 0.08% and 0.1% dopamine was analyzed by flow cytometry. The apoptosis-inducing effect of dopamine in vivo was also tested by intratumoral injection of 1% dopamine in 2 BALB/c-nu mice bearing A549 tumor xenograft using flow cytometry. RESULTS: The presence of dopamine receptor D2 expression was detected by Western blotting and RT-PCR in 95D, H460, GLC-82, A549 and H446 cells. Flow cytometry detected obvious apoptosis of A549 cells following dopamine exposure in vitro in positive correlation to dopamine concentration. In the tumor-bearing mice, dopamine also showed an obvious apoptosis-inducing effect on A549 cells. CONCLUSION: Dopamine receptor D2 exists extensively in different pulmonary carcinoma cells. Dopamine may promote the apoptosis of pulmonary carcinoma cells through dopamine receptor D2.

ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression.

Extracellular ATP released from axons is known to assist activity-dependent signaling between neurons and Schwann cells in the peripheral nervous system. Here we report that ATP released from astrocytes as a result of neuronal activity can also modulate central synaptic transmission. In cultures of hippocampal neurons, endogenously released ATP tonically suppresses glutamatergic synapses via presynaptic P2Y receptors, an effect that depends on the presence of cocultured astrocytes. Glutamate release accompanying neuronal activity also activates non-NMDA receptors of nearby astrocytes and triggers ATP release from these cells, which in turn causes homo- and heterosynaptic suppression. In CA1 pyramidal neurons of hippocampal slices, a similar synaptic suppression was also produced by adenosine, an immediate degradation product of ATP released by glial cells. Thus, neuron-glia crosstalk may participate in activity-dependent synaptic modulation.

[Clinical practice of 99mTc-peplimycin imaging and radio guided surgery for lung neoplasms].

BACKGROUND & OBJECTIVE: Intraoperatively,the routine method to differentiate malignant lung neoplasms from benign lesions is by the judgment of naked eye or frozen section. It is not accurate to judge by naked eye and will take long time by frozen section. Using a gamma-detecting probe (GDP) to accurately detect the tumors and the metastases, the operators could decide the resection range and the treatment plan. This study was preliminary clinical practice of tumor imaging and radioimmunoguided surgery (RGS) using (99m)Tc-PPM (peplomycin) as a tumor tracer. METHODS: Thirty-seven patients were administered with injection of (99m)Tc-PPM. The images were taken preoperatively. Region of interest (ROI) method was performed and tumor-to- normal-tissue (T/NT) ratio was calculated on the image. The radioactivity of the specimens resected from the patients was detected using GDP at the time of surgery. T/NT ratio was obtained by comparing the radioactivity of the tumor tissue with the normal lung tissue. RESULTS: The uptake ratios (T/NT) of (99m)Tc-PPM were different between malignant and benign lesion (P< 0.01). The ratio (T/NT, x+/-2s) was regarded as the threshold for differentiation of malignant and benign lesions. The sensitivity, specificity, and accuracy of identifying malignant lesion were 90%, 87.5%, and 89.3%, respectively; GDP could be used to accurately detect the invasive range of the tumors, with the sensitivity, specificity, and accuracy of identifying lymph node metastases of 91%, 88%, and 90%, respectively. CONCLUSION: (99m)Tc-PPM is a useful agent in differentiating malignant lung neoplasm from benign lesions, and as a tumor tracer can be used in detecting tumor by GDP intraoperatively. The RGS is a simple method that can help the surgeon in the intraoperative assessment of the tumor and the lymph node metastases.