Near-Unity Green Luminescent Hybrid Manganese Halides as X-ray Scintillators.

The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.

Population pharmacokinetics and dosing optimization of azlocillin in neonates with early-onset sepsis: a real-world study.

OBJECTIVES: Nowadays, real-world data can be used to improve currently available dosing guidelines and to support regulatory approval of drugs for use in neonates by overcoming practical and ethical hurdles. This proof-of-concept study aimed to assess the population pharmacokinetics of azlocillin in neonates using real-world data, to make subsequent dose recommendations and to test these in neonates with early-onset sepsis (EOS). METHODS: This prospective, open-label, investigator-initiated study of azlocillin in neonates with EOS was conducted using an adaptive two-step design. First, a maturational pharmacokinetic-pharmacodynamic model of azlocillin was developed, using an empirical dosing regimen combined with opportunistic samples resulting from waste material. Second, a Phase II clinical trial (ClinicalTrials.gov: NCT03932123) of this newly developed model-based dosing regimen of azlocillin was conducted to assure optimized target attainment [free drug concentration above MIC during 70% of the dosing interval ('70% fT>MIC')] and to investigate the tolerance and safety in neonates. RESULTS: A one-compartment model with first-order elimination, using 167 azlocillin concentrations from 95 neonates (31.7-41.6 weeks postmenstrual age), incorporating current weight and renal maturation, fitted the data best. For the second step, 45 neonates (30.3-41.3 weeks postmenstrual age) were subsequently included to investigate target attainment, tolerance and safety of the pharmacokinetic-pharmacodynamic model-based dose regimen (100 mg/kg q8h). Forty-three (95.6%) neonates reached their pharmacokinetic target and only two neonates experienced adverse events (feeding intolerance and abnormal liver function), possibly related to azlocillin. CONCLUSIONS: Target attainment, tolerance and safety of azlocillin was shown in neonates with EOS using a pharmacokinetic-pharmacodynamic model developed with real-world data.

First dose in neonates: pharmacokinetic bridging study from juvenile mice to neonates for drugs metabolized by CYP3A.

First dose prediction is challenging in neonates. Our objective in this proof-of-concept study was to perform a pharmacokinetic (PK) bridging study from juvenile mice to neonates for drugs metabolized by CYP3A. We selected midazolam and clindamycin as model drugs. We developed juvenile mice population PK models using NONMEM. The PK parameters of these two drugs in juvenile mice were used to bridge PK parameters in neonates using different correction methods. The bridging results were evaluated by the fold-error of 0.5- to 1.5-fold. Simple allometry with and without a correction factor for maximum lifespan potential could be used for a bridging of clearance (CL) and volume of distribution (Vd), respectively, from juvenile mice to neonates. Simulation results demonstrated that for midazolam, 100% of clinical studies for which both the predictive CL and Vd were within 0.5- to 1.5-fold of the observed. For clindamycin, 75% and 100% of clinical studies for which the predictive CL and Vd were within 0.5- to 1.5-fold of the observed. A PK bridging of drugs metabolized by CYP3A is feasible from juvenile mice to neonates. It could be a complement to the ADE and PBPK models to support the first dose in neonates.

Long Noncoding RNA-Sox2OT Knockdown Alleviates Diabetes Mellitus-Induced Retinal Ganglion Cell (RGC) injury.

Retinal ganglion cell (RGC) injury is one of the important pathological features of diabetes-induced retinal neurodegeneration. Increasing attention has been paid to find strategies for protecting against RGC injury. Long noncoding RNAs (lncRNAs) have emerged as the key regulators of many cell functions. Here, we show that Sox2OT expression is significantly down-regulated in the retinas of STZ-induced diabetic mice and in the RGCs upon high glucose or oxidative stress. SOX2OT knockdown protects RGCs against high glucose-induced injury in vitro. Moreover, Sox2OT knockdown plays a neuroprotective role in diabetes-related retinal neurodegeneration in vivo. Sox2OT knockdown could regulate oxidative stress response in RGCs and diabetic mouse retinas. Sox2OT knockdown plays an anti-oxidative role via regulating NRF2/HO-1 signaling activity. Taken together, Sox2OT knockdown may be a therapeutic strategy for the prevention and treatment of diabetes-induced retinal neurodegeneration.

Lignans Extracted from Eucommia Ulmoides Oliv. Protects Against AGEs-Induced Retinal Endothelial Cell Injury.

BACKGROUND/AIMS: Advanced glycation end products (AGEs) could elicit oxidative stress, trigger and aggravate endothelium damage in several ischemic retinopathies including diabetic retinopathy (DR). The leaves of Eucommia ulmoides O., also referred to as Tu-chung or Du-zhong, have been used for the treatment of hypertension and diabetes, showing great antioxidant activity and anti-glycation activity. Lignans is one of the main bioactive components of Eucommia ulmoides. This study mainly investigated the effect of lignans treatment on AGEs-induced endothelium damage. METHODS: MTT assay, Hoechst staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of lignans treatment on endothelial cell function in vitro. Retinal trypsin digestion, Evans blue assay, isolectin staining, and western blots were conducted to determine the effect of lignans treatment on retinal microvascular function in vivo. Western blot, protein immunoprecipitation (IP), MTT assays, and enzyme activity assay was conducted to detect the effect of ligans treatment on oxidative stress response. RESULTS: Lignans protected retinal endothelial cell against AGEs-induced injury in vitro and diabetes-induced vascular dysfunction in vivo. Lignans treatment could regulate oxidative stress response in retinal endothelial cell line, retina, and liver. Moreover, we showed that NRF2/HO-1 signaling was critical for lignans-mediated oxidative stress regulation. CONCLUSION: Lignans treatment could protect against endothelial dysfunction in vivo and in vitro via regulating Nrf2/HO-1 signaling. Lignans might be developed as a promising drug for the treatment of diabetes-induced microvascular dysfunction.

Highly Enantioselective Catalysis by Enzyme Encapsulated in Metal Azolate Frameworks with Micelle-Controlled Pore Sizes.

Encapsulating enzymes within metal-organic frameworks has enhanced their structural stability and interface tunability for catalysis. However, the small apertures of the frameworks restrict their effectiveness to small organic molecules. Herein, we present a green strategy directed by visible linker micelles for the aqueous synthesis of MAF-6 that enables enzymes for the catalytic asymmetric synthesis of chiral molecules. Due to the large pore aperture (7.6 Å), double the aperture size of benchmark ZIF-8 (3.4 Å), MAF-6 allows encapsulated enzyme BCL to access larger substrates and do so faster. Through the optimization of surfactants' effect during synthesis, BCL@MAF-6-SDS (SDS = sodium dodecyl sulfate) displayed a catalytic efficiency (Kcat/Km) that was 420 times greater than that of BCL@ZIF-8. This biocomposite efficiently catalyzed the synthesis of drug precursor molecules with 94-99% enantioselectivity and nearly quantitative yields. These findings represent a deeper understanding of de novo synthetic encapsulation of enzyme in MOFs, thereby unfolding the great potential of enzyme@MAF catalysts for asymmetric synthesis of organics and pharmaceuticals.

Hepatocellular carcinoma that arose from primary Sjögren's syndrome.

Hepatocellular carcinoma (HCC) typically originates from HBV or HCV associated liver cirrhosis. Primary Sjögren's syndrome (pSS) is a kind of autoimmune disease. A sixty-two year old female patient with mild liver damage was diagnosed with pSS after excluding viral, alcoholic and drug-induced hepatitis according to serum immunological detection and liver biopsy. But when she was hospitalized for a second time two years later, a CT scan revealed liver neoplasm. Surgery confirmed HCC and liver cirrhosis by pathology. The elevated level of AFP recovered to normal after tumorectomy. In conclusion, HCC might be a candidate outcome in patients with pSS; it is the doctors' responsibility to keep this kind of patient under surveillance.

[Effects of Different Nitrite Generation on the Short-cut Nitrification Denitrifying Phosphorus Removal Granules System].

To explore the effects of nitrite generation on the system of short-cut nitrification denitrifying phosphorus removal granules, nitrite was produced continuously and intermittently, under continuous and intermittent aeration, in two groups of SBR reactors of the same size. The effects of nitrogen and phosphorus removal, physical characteristics of the sludge, and microbial community structure were investigated. Nitrite was consumed immediately after intermittent production, with better and more stable nitrogen and phosphorus removal performance. In particular, the average rate of TN removal was 92.07% after 72 days. The utilization efficiency of the carbon source (by P/COD) was concentrated at 0.21-0.22 mg ·mg-1, to ensure full utilization of the carbon source and to further promote denitrification and phosphorus removal. Particle sizes were uniform and showed concentrated distribution, with particles exhibiting regular shapes and clear boundaries. Microbial community analysis showed that the abundance and diversity of microbial communities were higher in the intermittent nitrite system and more enriched in DPAOs genera (Dechloromonas and Pseudomonas). The combination of DPAOs genera and Nitrosomonas resulted in a dynamic balance and stable operation of the short-cut nitrification and denitrifying phosphorus removal system.

[Combining Different Aerobic/Anoxic Durations with Zoned Sludge Discharge to Optimize Short-cut Nitrification Denitrifying Phosphorus Removal Granules in Domestic Sewage].

In this study, domestic sewage was used to inoculate mature short-cut nitrification denitrifying phosphorus removal particles, which were cultivated and matured under artificial water. The operation of the short-cut nitrification denitrifying phosphorus removal system was optimized using different aerobic/anoxic durations combined with zoned sludge discharge. The results showed that regulating the aerobic/anoxic duration, in combination with zoned sludge discharge, can realize the stable operation of the system. In the later stable period, the effluent COD concentration was below 50 mg·L-1, the effluent TN concentration was below 15 mg·L-1, the TN removal rate reached about 83% and remained stable, the effluent P concentration was below 0.5 mg·L-1, and the average P removal rate was 93.72%. At the same time, zoned sludge discharge (70% top sludge and 30% bottom sludge) can be used to screen out microorganisms, maintain good nitrosation and phosphorus removal performance, limit the particle size distribution, and ensure the growth advantages of AOB and DPAOs. Increases in the anoxic duration improved the growth rate of anoxic heterotrophic bacteria, causing them to secrete more EPS and ensuring granular sludge improvements and continued stability.

[Simultaneous Domestication of Short-cut Nitrification Denitrifying Phosphorus Removal Granules].

In this experiment, three replicated SBR reactors were operated using asynchronous acclimation of the phased method (A/O-A/O/A), simultaneous domestication of continuous aeration by A/O/A, and simultaneous domestication of intermittent aeration by A/O/A. Using artificial water distribution as the influent substrate, flocculent sludge was inoculated and granulated by hydraulic selection. The domestication and nitrogen and phosphorus removal characteristics of shortcut nitrification denitrifying phosphorus removal granules under different operation modes were assessed. The results show that simultaneous domestication of intermittent aeration by A/O/A has the most efficient under the combination of short aeration time (140 min) and low aeration strength[3.5 L·(h·L)-1]. The average removal rates of carbon, nitrogen, and phosphorus were 90.74%, 91.15%, and 95.66%, respectively, which could achieve synchronous removal during later stable operation. The particle size was 895 µm, and the particles were small but uniformly dense in microscope observations. The f value (MLVSS/MLSS) was kept stable at 0.8-0.85 and sludge had a high biomass due to the alternate aerobic/anoxic operation with intermittent aeration. This supported anoxic heterotrophic bacteria at the core of the particles, which was conducive to the stability of the granular sludge structure. Batch experiments showed that the specific ammonia-oxidation rate of the simultaneous domestication of intermittent aeration by A/O/A system was 3.38 mg·(g·h)-1, and denitrifying phosphate accumulating organisms (DPAOs) able to utilize nitrite as electron acceptor accounted for 65.46%. This was more conducive to the simultaneous domestication and enrichment of ammonia-oxidizing bacteria (AOB) and NO2--type DPAOs, ensuring a stable treatment effect.

Developmental Pharmacogenetics of CYP2D6 in Chinese Children: Loratadine as a Substrate Drug.

Objective: The elucidation of CYP2D6 developmental pharmacogenetics in children has improved, however, these findings have been largely limited to studies of Caucasian children. Given the clear differences in CYP2D6 pharmacogenetic profiles in people of different ancestries, there remains an unmet need to better understand the developmental pharmacogenetics in populations of different ancestries. We sought to use loratadine as a substrate drug to evaluate the effects of ontogeny and pharmacogenetics on the developmental pattern of CYP2D6 in Chinese pediatric patients. Methods: Chinese children receiving loratadine treatment were enrolled in the present study. The metabolite-to-parent ratio (M/P ratio), defined as the molar ratio of desloratadine to loratadine of trough concentrations samples at steady-state condition, was used as a surrogate of CYP2D6 activity. Loratadine and desloratadine were determined by LC/MS/MS method. Variants of CYP2D6 were genotyped by polymerase chain reaction for CYP2D6 *4, *10, *41 and long polymerase chain reaction for CYP2D6 *5. Results: A total of 40 patients were available for final analysis. The mean age was 4.50 (range 0.50-9.00) years and the mean weight was 19.64 (range 7.00-42.00) kg. The M/P ratio was significantly lower in intermediate metabolizers (IMs) compared to normal metabolizers (NMs) (10.18 ± 7.97 vs. 18.80 ± 15.83, p = 0.03). Weight was also found to be significantly associated with M/P ratio (p = 0.03). Conclusion: The developmental pharmacogenetics of CYP2D6 in Chinese children was evaluated using loratadine as a substrate drug. This study emphasizes the importance of evaluating the developmental pharmacogenetics in populations of different ancestries.

LPS-Induced Inflammation Affects Midazolam Clearance in Juvenile Mice in an Age-Dependent Manner.

PURPOSE: Inflammation has a significant impact on CYP3A activity. We hypothesized that this effect might be age dependent. Our objective was to conduct a population pharmacokinetic study of midazolam in mice at different developmental stages with varying degrees of inflammation to verify our hypothesis. METHODS: Different doses (2 and 5 mg/kg) of lipopolysaccharide (LPS) were used to induce different degrees of systemic inflammation in Swiss mice (postnatal age 9-42 days, n = 220). The CYP3A substrate midazolam was selected as the pharmacological probe to study CYP3A activity. Postnatal age, current body weight, serum amyloid A protein 1 (SAA1) levels and LPS doses were collected as covariates to perform a population pharmacokinetic analysis using NONMEM 7.2. RESULTS: A population pharmacokinetic model of midazolam in juvenile and adult mice was established. Postnatal age and current body weight were the most significant and positive covariates for clearance and volume of distribution. LPS dosage was the most significant and negative covariate for clearance. LPS dosage can significantly reduce the clearance of midazolam by 21.8% and 38.7% with 2 mg/kg and 5 mg/kg, respectively. Moreover, the magnitude of the reduction was higher in mice with advancing postnatal age. CONCLUSION: Both inflammation and ontogeny have an essential role in CYP3A activity in mice. The effect of LPS-induced systemic inflammation on midazolam clearance in mice is dependent on postnatal age.

Drug Clearance in Neonates: A Combination of Population Pharmacokinetic Modelling and Machine Learning Approaches to Improve Individual Prediction.

BACKGROUND: Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data. OBJECTIVE: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates. METHODS: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods. RESULTS: The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods. CONCLUSION: A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data.

[Simultaneous Short-Cut Nitrification-Denitrification Phosphorus Removal Granules Induced by Phosphorus Removal Granules].

This paper investigated domestic sewage with a low C/N ratio. Mature phosphorus removal granules were inoculated to cultivate granules with a simultaneous short-cut nitrification and denitrification function. The characteristics of nitrogen and phosphorus removal of this process were analyzed. Results show that AOB can be enriched by prolonging the sludge age for 30 days with an aeration intensity of 5 L·(h·L)-1 and shorter aeration time (140 min), whereas the simultaneous nitrification and denitrification ability could not be improved. The nitrogen loss increased at the aerobic time when aeration intensity was reduced by 3.5 L·(h·L)-1 and aeration time was prolonged by 200 min. The aeration time was further optimized to restrain the transformation of NO2- to NO3-, and finally the effluent of TP < 0.5 mg·L-1 and TN < 15 mg·L-1. During the process of the system function transformation from phosphorus removal to nitrogen and phosphorus removal, the phosphorus release decreased, however PAOs still played a dominant role (60%) in the process of internal carbon storage. Batch experiments showed that DPAOs that can utilize nitrite as an electron acceptor accounts for 52.43% in the total PAOS, which alleviated the pressure of the carbon source and improved the simultaneous nitrogen and phosphorus removal.

An adapted LC-MS/MS method for the determination of free plasma concentration of cefoperazone in children: Age-dependent protein binding.

Antimicrobial activity of cefoperazone, a high protein bound cephalosporin, depends on its unbound concentration. However, the protein binding data of cefoperazone in children is limited, making it challenging to optimize antimicrobial therapy in pediatric clinical practice. Furthermore, a validated method to measure the free part in children is unavailable with the small volume of samples that can be obtained. Therefore, in the present study, we developed and validated an LC-MS/MS method for the determination of free cefoperazone in children. In this study, 70 µL of plasma was used to prepare the ultrafiltrate (only containing the free drug). Chromatographic separation of the analyte was achieved on a C18 column using gradient elution with a mobile phase of acetonitrile and water (0.1% formic acid). Negative electrospray ionisation in the multiple reaction monitoring mode was applied for the detection of cefoperazone and ceftiofur (internal standard). The calibration curve was prepared in the range of 5-5000 ng/mL with excellent linearity. For each level of quality control samples, the intra- and inter-day precision (CV) was below 9.0%, and the accuracy ranged from 91.5% to 105.0%. The matrix effect was less than 11.7%, and the recovery was between 92.9% and 95.9% of cefoperazone. The validated method has been successfully applied to the determination of free plasma concentration of cefoperazone in pediatric patients. The results of the unbound fraction showed considerable individual variability (range: 8.1-48.0%). The correlation analysis showed that age and albumin had significant effects on the protein binding of cefoperazone.

[Effects of Solid Retention Time on the Phosphorus Removal and Nitrosation Granules System].

In this paper, the low C/N ratio of domestic sewage was studied, and mature phosphorus removal granules were inoculated to investigate the effect of solid retention time(SRT)on phosphorus removal and nitrification granular sludge at middle-low temperatures (14-21℃). The test showed that at room temperature (20℃±1℃), the enrichment of AOB in the phosphorus removal granules can be achieved with 30 d SRT and 5 L·(h·L)-1 aeration intensity, while the NAR was over 90%. When the temperature was lowered to 15℃ and the SRT was 40 d, the phosphorus removal performance deteriorated, and the granule structure became loose with the formation of filamentous bacteria. Relatively sufficient oxygen destabilized nitrosation and the NAR dropped by 22.4%. NOB does not have the ability to quickly adapt to environmental changes. The 12 d anaerobic starvation and sludge removal strategy weakened the relative activity of NOB and quickly restored the performance of phosphorus removal and nitrosation. Batch experiments showed that the temperature dropped from 20℃ to 15℃, and the PAOs still maintained a high oxygen utilization rate, but the SOUR of the AOB decreased by 18%. At this time, the temperature, not the dissolved oxygen concentration, restricted the ammonia oxidation ability. Controlling the sludge age to 30 d, while reducing the aeration intensity to 4 L·(h·L)-1, achieved stable operation of phosphorus removal and nitrosation at a low temperature (15℃±1℃).

Elevated levels of serum soluble E-selectin in patients with chronic hepatitis B: Correlation with T lymphocyte subsets, NK cells and liver inflammation.

BACKGROUND: It has been reported that serum soluble E-selectin (sE-selectin) may be increased in some inflammatory liver diseases. The purpose of our study was to investigate changes of sE-selectin, T lymphocyte subsets, natural killer (NK) cells, and HBV load in patients with chronic hepatitis B (CHB), analyze the relationship between them, and discuss their significances. METHODS: Fifty-four patients with chronic hepatitis B and fourteen controls were studied. Serum sE-selectin, T lymphocyte subsets, NK cells, and hepatitis B virus (HBV) load were detected by enzyme-linked immunosorbent assay (ELISA), flow cytometry (FCM), and fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. RESULTS: sE-selectin level in patients with CHB increased significantly than that in controls (p<0.01). The percentages of CD4 positive cells and NK cells decreased while the percentage of CD8 positive cells increased significantly in CHB patients than in controls (p<0.01, respectively). sE-selectin level significantly related to levels of T lymphocyte subsets, NK cells, serum alanine aminotransferase (sALT) and aspartate aminotransferase (sAST) (p<0.01, respectively), but had no relationship with HBV level. CONCLUSION: The sE-selectin levels in patients with chronic hepatitis B increase significantly and correlate to liver inflammation, suggesting that sE-selectin can be considered as an additional useful marker of CHB inflammatory activity, and E-selectin may play part of role in pathogenesis of chronic hepatitis B.

[A clinical study of abnormal bone metabolism in patients with HBV liver cirrhosis].

OBJECTIVE: To study the pathogenesis of abnormal bone metabolism in patients with HBV liver cirrhosis. METHODS: NM-300 signal-energy X-ray absorptiometry system was used to measure the bone mineral density (BMD) in 61 liver cirrhosis patients and 30 age-matched healthy controls. The serum levels of 1,25(OH)2D3, parathyroid hormone (PTH), calcitonin (CT), bone gamma-carboxyglutamic acid-containing protein (BGP), IL-1beta, IL-6, tumor necrosis factor (TNF)alpha and urine crosslaps were also detected in these patients. RESULTS: BMD in patients with HBV liver cirrhosis was lower than those of the controls. The serum levels of 1,25(OH)2D3 and BGP in cirrhosis patients were lower than those in the controls, and they were much lower in the osteoporosis (OP) group than in the non-osteoporosis (NOP) group. The PTH and CT were higher significantly in the patients than in the controls. The changes of serum 1,25(OH)2D3 and BGP were correlated with the changes of BMD. The serum levels of IL-1beta, IL-6, TNFalpha and urine crosslaps in cirrhosis patients were higher than those of the controls, and they were much higher in the OP group than in the NOP group. We also found that the serum levels of IL-1beta, IL-6, TNFalpha and urine crosslaps had a negative correlation with BMD. CONCLUSIONS: These data suggest that bone formation is weakened and bone resorption is increased in patients with HBV liver cirrhosis, 1,25(OH)2D3 plays an important role in abnormal bone formation. Elevation of serum IL-1beta, IL-6, TNFalpha can accelerate bone resorption and cause hepatic bone disease (HBD). Taking 1,25(OH)2D3 and reducing the level of IL-1beta, IL-6, TNFalpha may be very important in preventing and treating HBD.

Pharmacodynamic study on insomnia-curing effects of Shuangxia Decoction in Drosophila melanogaster.

The present study aimed to establish a pharmacodynamic method using the pySolo software to explore the influence of freeze-dried powders of Shuangxia Decoction (SXD) on the sleep of normal Drosophila melanogaster and the Drosophila melanogaster whose sleep was divested by light. The dose-effect and the time-effect relationships of SXD on sleep were examined. The effect-onset concentration of SXD was 0.25%, the plateau appeared at the concentration of 2.5% and the total sleep time showed a downtrend when the concentration was greater than 2.5%. The sleep time was the longest on the fourth day after SXD was given. The fruit fly sleep deprivation model was repeated by light stimulation at night. The middle dosage group (2.5%) had the best insomnia-curing effect. In conclusion, using the pySolo software, an approach for the pharmacodynamics study was established with Drosophila melanogaster as a model organism to determine the insomnia-curing effects of the traditional Chinese medicine (TCM). Our results demonstrated the reliability of this method. The freeze-dried powders of SXD could effectively improve the sleep quality of Drosophila melanogaster.

[A study of the association of iNOS and eNOS gene polymorphism with portal hypertension in liver cirrhosis].

OBJECTIVE: To study whether polymorphism of iNOS and eNOS genes is associated with portal hypertension in liver cirrhosis. METHODS: A case control study of 106 patients with liver cirrhosis due to HBV was performed in comparison with 108 controls using PCR-RFLP to detect iNOS promoter -969G --> C and eNOS exon7 894G --> T polymorphism. RESULTS: The frequency of the C allele and GC genotype in the iNOS promoter -969G --> C was significantly higher in the portal hypertension group than in the control group. (P < 0.05). The frequency of the T allele and GT genotype in eNOS exon7 894G --> T was dramatically higher in the portal hypertension group than in the control group (P < 0.05). Multivariate logistic regression analysis revealed that iNOS polymorphism in iNOS promoter -969G --> C and eNOS exon7 894G --> T was an independent new risk factor for portal hypertension. We discovered that iNOS promoter -969G --> C led to an increase in its functional activity. CONCLUSIONS: The polymorphism of iNOS promoter -969G --> C and eNOS exon7 894G --> T is associated with portal hypertension of liver cirrhosis, which is a new independent risk factor found related to the occurrence of portal hypertension. The polymorphism of iNOS promoter -969G --> C results in functional activity increase of the iNOS promoter.