Research progress in rodent modeling of major depressive disorder / 中国药理学通报

Major depressive disorder (MDD) has a high disability rate and a high risk of suicide. Due to the limited efficacy of traditional antidepressants, researchers have actively developed animal models with different mechanisms to meet the clinical needs. The principle and preparation methods, phenotypic characteristics, model validity (simulating clinical MDD) and their advantages and disadvantages of different models have been reviewed in this article. It is helpful for researchers to explore the pathogenesis of MDD and to select appropriate animal models in the development of new anti-MDD drugs.

Genetic Profiles in Pharmacogenes Indicate Personalized Drug Therapy for COVID-19

BackgroundThe coronavirus disease 2019 (COVID-19) has become a global pandemic currently. Many drugs showed potential for COVID-19 therapy. However, genetic factors which can lead to different drug efficiency and toxicity among populations are still undisclosed in COVID-19 therapy. MethodsWe selected 67 potential drugs for COVID-19 therapy (DCTs) from clinical guideline and clinical trials databases. 313 pharmaco-genes related to these therapeutic drugs were included. Variation information in 125,748 exomes were collected for racial differences analyses. The expression level of pharmaco-genes in single cell resolution was evaluated from single-cell RNA sequencing (scRNA-seq) data of 17 healthy adults. ResultsPharmacogenes, including CYP3A4, ABCB1, SLCO1B1, ALB, CYP3A5, were involved in the process of more than multi DCTs. 224 potential drug-drug interactions (DDIs) of DCTs were predicted, while 112 of them have been reported. Racial discrepancy of common nonsynonymous mutations was found in pharmacogenes including: VDR, ITPA, G6PD, CYP3A4 and ABCB1 which related to DCTs including ribavirin, -interferon, chloroquine and lopinavir. Moreover, ACE2, the target of 2019-nCoV, was only found in parts of lung cells, which makes drugs like chloroquine that prevent virus binding to ACE2 more specific than other targeted drugs such as camostat mesylate. ConclusionsAt least 17 drugs for COVID-19 therapy with predictable pharmacogenes should be carefully utilized in risk races which are consisted of more risk allele carriers. At least 29 drugs with potential of DDIs are reported to be affected by other DDIs, they should be replaced by similar drugs without interaction if it is possible. Drugs which specifically targeted to infected cells with ACE2 such as chloroquine are preferred in COVID-19 therapy.

Treatment of severely osteoporotic vertebral compression fractures with the vertebral body stent system and percutanous kyphoplasty combined with zoledronic acid / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy of vertebral body stent (VBS) system and percutanous kyphoplasty (PKP) combined with zoledronic acid for the treatment of severely osteoporotic compression vertebral fractures (OVCFs).@*METHODS@#The clinical data of 48 patients with osteoporotic thoracolumbar fractures treated from December 2017 to December 2018 were retrospectively analyzed, including 13 males and 35 females, aged 55 to 92 years old with an average (71.2±10.5) years. All patients were treated with VBS system PKP surgery, and zoledronic acid injection was used for anti-osteoporosis treatment after operation. The VAS scores ODI, the height of diseasedvertebral lost were compared before operation, 3 d and half a year after operation, and whether there was re-fracture of diseased or adjacent vertevrae after operation was observed.@*RESULTS@#Before operation, 3 d and half a year after operation, VAS scores were 7.60±0.12, 3.00±0.46, 1.20±0.23, ODI were(82.00±0.32)%, (30.00±1.50) %, (18.00±0.16) %, the height of diseased vertebral lost were (12.00±0.43) mm, (3.00± 0.15) mm, (3.60±0.51) mm respectively. Postoperative VAS score, ODI, the height of diseased vertebral lost were obviously improved (0.05). All the 48 patients were followed up with an average time of (6.6±0.5) months. All the incisions healed at grade A after operation, and no re-fracture of diseased vertebrae or adjacent vertebrae was found at the final follow-up.@*CONCLUSION@#VBS system and PKP combined with zoledronic acid in the treatment of OVCFs not only may effectively relieve the pain in the thoracolumbar back, improve the mobility of the thoracolumbar, but also can restore the height of the vertebral body to the maximum extent, and prevent the re-fracture of the affected vertebrae and adjacent vertebrae, which is worthy to spread in clinic.

Liraglutide Ameliorates Hyperhomocysteinemia-Induced Alzheimer-Like Pathology and Memory Deficits in Rats via Multi-molecular Targeting / 神经科学通报·英文版

Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD), and insulin-resistance is commonly seen in patients with Hhcy. Liraglutide (Lir), a glucagon-like peptide that increases the secretion and sensitivity of insulin, has a neurotrophic or neuroprotective effect. However, it is not known whether Lir ameliorates the AD-like pathology and memory deficit induced by Hhcy. By vena caudalis injection of homocysteine to produce the Hhcy model in rats, we found here that simultaneous administration of Lir for 2 weeks ameliorated the Hhcy-induced memory deficit, along with increased density of dendritic spines and up-regulation of synaptic proteins. Lir also attenuated the Hhcy-induced tau hyperphosphorylation and Aβ overproduction, and the molecular mechanisms involved the restoration of protein phosphatase-2A activity and inhibition of β- and γ-secretases. Phosphorylated insulin receptor substrate-1 also decreased after treatment with Lir. Our data reveal that Lir improves the Hhcy-induced AD-like spatial memory deficit and the mechanisms involve the modulation of insulin-resistance and the pathways generating abnormal tau and Aβ.

Molecular evidence for nitrite-dependent anaerobic methane-oxidising bacteria in the Jiaojiang Estuary of the East Sea (China).

Nitrite-dependent anaerobic methane oxidation (N-DAMO) is a recently discovered process linking the global carbon and nitrogen cycles. This process was reported to be mediated by "Candidatus Methylomirabilis oxyfera". To date, M. oxyfera-like bacteria have been detected in a limited number of freshwater habitats, but whether these bacteria occur in estuarine habitats is currently unknown. In this study, the distribution, diversity and abundance of M. oxyfera-like bacteria were studied in the sediment of the Jiaojiang Estuary of the East Sea (China). Both the 16S ribosomal RNA (rRNA) and pmoA genes confirmed the occurrence of M. oxyfera-like bacteria in the examined estuary. The recovered 16S rRNA gene sequences showed 91.5-97.2 % identity to the 16S rRNA gene of M. oxyfera, and the recovered pmoA gene sequences showed 85.1-95.4 % identity to the pmoA gene of M. oxyfera. Quantitative PCR further confirmed the occurrence of M. oxyfera-like bacteria in this estuary, with the abundance varying from 5.80 ± 0.28 × 10(4) to 8.35 ± 0.52 × 10(7) copies g (dry weight)(-1). Correlation analysis indicated that the sediment organic content was the most important factor affecting the distribution of M. oxyfera-like bacterial communities in the examined sediments among the environmental factors investigated. This study demonstrated for the first time the existence of M. oxyfera-like bacteria in an estuarine environment and showed the correlations between the distribution of these bacteria and the estuarine environmental conditions.

Determination of plasma concentration of five phenolic acid by LC-MS/MS and study of pharmacokinetics in rats after Mailuoning injection / 中国中药杂志

To establish a LC-MS/MS method for quantification of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in rats plasma and study its pharmacokinetics after administration of Mailuoning injection at a single dose to rats. Plasma samples were acidified with hydrochloric acid and extracted with ethyl acetate. The analytes were determined by LC-MS-MS using a ZOBAX SB C18 column with a mobile phase of methanol-water (containing 2 mmol x L(-1) ammonium acetic) (60:40)at a flow rate of 0.5 mL x min(-1) and detected using ESI with negative ionization mode. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 353.1/191.0 [M-H]- for chlorogenic acid, m/z 178.9/134.9 [M-H]- for caffeic acid, m/z 515.2/353.0 [M-H]-for 3,4-DCQA, m/z 193.0/133.9 [M-H]-for ferulic acid, m/z 146.9/102.9 [M-H]- for cinnamic acid and m/z 246.0/125.8 [M-H]- for tinidazole (IS). After administration of Mailuoning injection at a single dose to eight Sprague-Dawley rats, the concentrations of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in plasma were determined by LC-MS/MS method. The main pharmacokinetics parameters of measured data were caluculated by using DASver 1.0 software. The linear concentration ranges of the calibration curves for chlorogenic acid, caffeic acid, 3,4-DCQA and cinnamic acid were 2.006-1,027 microg x L(-1) (r = 0.999 6), 1.953-1,000 microg x L(-1) (r = 0.999 7), 28.51-1.459 x 10(4) microg x L(-1) (r = 0.998 9), 1.836-940.0, g x L(-1) (r = 0.997 7) and 4.780-2,447 microg x L(-1) (r = 0.998 6) respectively. The inner and inter-days relative standard deviations were both less than 5.0%, indicating legitimate precise and accuracy to the requirement of biological sample analysis. For chlorogenic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (49.78 +/- 12.81) min, (123.55 +/- 14.82) mg x min x L(-1) and (0.004 3 +/- 0.000 5) L x min(-1), respectively. For caffeic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (36.65 +/- 10.59) min, (91.67 +/- 11.77) mg x min L(-1) and (0.005 7 +/- 0.000 7) L x min(-1), respectively. For 3,4-DCQA, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (50.08 +/- 13.78) min, (278.34 +/- 31.82) mg x min x L-1 and (0.001 6 +/- 0.000 2) L x min(-1), respectively. For ferulic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (51.39 +/- 15.52) min, (34.72 +/- 4.67) mg x min x L(-1) and (0.000 4 +/- 0.0001) L x min(-1), respectively. For cinnamic acid, the pharmacokinetic parameter t1/2, AUCo-t, and CL were (74.42 +/- 18.32) min, (34.63 +/- 4.82) mg x min x L(-1) and (0.007 7 +/- 0.001 1) L x min-', respectively. The assay method is proved to be sensitive, accurate and convenient. It can be applied to the pharmacokinetic study of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid.

Systematic report on re-evaluating parenterally administered salvianolate / 中国中药杂志

There are few articles or reports collecting evidence about parenterally administered salvianolate from premarketing and postmarketing research or studies systematically. This article is an exact miniature of a systematical report about parenterally administered salvianolate. We analyzed information from four aspects, such as quality control reports, non-clinical premarketing safety experiments, postmarketing research (efficacy studies, hospital information system data and national spontaneous reporting system data) and literature analysis. All the four aspects build an evidence body for Kudiezi Solution in order to inform its safety use in clinical practice and further study.

Enrichment of anammox bacteria from three sludge sources for the startup of monosodium glutamate industrial wastewater treatment system.

Three activated sludges from a landfill leachate treatment plant (S1), a municipal sewage treatment plant (S2) and a monosodium glutamate (MSG) wastewater treatment plant (S3) were used as inocula to enrich anaerobic ammonium oxidation (anammox) bacteria for the startup of MSG industrial wastewater treatment system. After 360 days of cultivation using MSG wastewater, obvious anammox activity was observed in all three cultures. The maximum specific anammox activities of cultures S1, S2 and S3 were 0.11 kg N kg(-1) VSS day(-1), 0.09 kg N kg(-1) VSS day(-1) and 0.16 kg N kg(-1) VSS day(-1), respectively. Brownish-red anammox granules having diameters in the range of 0.2-1.0mm were visible in cultures S1 and S2, and large red granules having diameters in the range of 0.5-2.5mm were formed in culture S3 after 420 days of cultivation. Phylogenetic analysis of 16S rRNA genes showed that Kuenenia organisms were the dominant anammox species in all three cultures. The copy numbers of 16S rRNA genes of anammox bacteria in cultures S1, S2 and S3 were 6.8 × 10(7) copies mL(-1), 9.4 × 10(7) copies mL(-1) and 7.5 × 10(8) copies mL(-1), respectively. The results of this study demonstrated that anammox cultivation from conventional activated sludges was highly possible using MSG wastewater. Thus the anammox process has possibility of applying to the nitrogen removal from MSG wastewater.

Surgical treatment of ankle fracture in the elderly / 中国骨伤

<p><b>OBJECTIVE</b>To analysis the outcomes and the technique of surgical operation of osteoporotic ankle fracture in the elderly.</p><p><b>METHODS</b>One hundred and twenty-eight patients with osteoporotic ankle fracture were treated by surgical operation from January 2003 to December 2008, included 26 males and 102 females, with an average age of 69 years old ranging from 50 to 82 years. According to Lange-Hanson classification, there were 113 cases of supinatio-extorsion, 18 of pronate-extorsion, 5 of supinatio-adduction, 2 of pronate-abduction. The methods of fixation, the complications, and the AOFAS scores after operation were recorded.</p><p><b>RESULTS</b>All the 128 patients were followed up from 6 months to 6 years (averaged in 36 months). Delayed wound healing occurred in 11 cases (8.6%). There was no deep infection, nonunion of the fracture, and revision. The average AOFAS scores after operation was 83.6 +/- 6.3 (the mean pain scores were 33.5 +/- 5.6, the mean function scores were 40.2 +/- 7.4, the mean alignment scores were 10).</p><p><b>CONCLUSION</b>Surgical treatment should be the first choice in osteoporotic ankle fracture in most cases. Improved procedures can make the results better.</p>

Preliminary construction of three-dimensional visual educational system for clinical dentistry based on world wide web webpage / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To establish a new visual educational system of virtual reality for clinical dentistry based on world wide web (WWW) webpage in order to provide more three-dimensional multimedia resources to dental students and an online three-dimensional consulting system for patients.</p><p><b>METHODS</b>Based on computer graphics and three-dimensional webpage technologies, the software of 3Dsmax and Webmax were adopted in the system development. In the Windows environment, the architecture of whole system was established step by step, including three-dimensional model construction, three-dimensional scene setup, transplanting three-dimensional scene into webpage, reediting the virtual scene, realization of interactions within the webpage, initial test, and necessary adjustment.</p><p><b>RESULTS</b>Five cases of three-dimensional interactive webpage for clinical dentistry were completed. The three-dimensional interactive webpage could be accessible through web browser on personal computer, and users could interact with the webpage through rotating, panning and zooming the virtual scene.</p><p><b>CONCLUSIONS</b>It is technically feasible to implement the visual educational system of virtual reality for clinical dentistry based on WWW webpage. Information related to clinical dentistry can be transmitted properly, visually and interactively through three-dimensional webpage.</p>

Preparation of doxorubicin-loaded chitosan polymeric micelle and study on its tissue biodistribution in mice / 药学学报

To prepare doxorubicin-loaded N-octyl-N'-succinyl chitosan polymeric micelle (DOX-OSC) and study the biodistribution of DOX-OSC in mice, DOX-OSC was prepared by dialysis method. By using doxorubicin injection (DOX-INJ) as control, DOX-OSC and DOX-INJ were administered to mice through caudal vein at a dose of 5 mg x kg(-1) body weight. The RP-HPLC method was established to determine the DOX levels in the plasma and other tissues of mice. The tissues distribution and targeting efficiency were evaluated by pharmacokinetic parameters (AUC, MRT) and targeting parameters (Re, Ce and Te). The drug loading and entrapment efficiency of DOX-OSC were (35.8 +/- 0.4)% and (75.3 +/- 1.1)%, respectively. The diameter and zeta potential of DOX-OSC were (174 +/- 12) nm and (-37.1 +/- 3.0) mV, respectively. The transmission electron microscope result showed DOX-OSC with spherical shape. The biodistribution results showed that the concentration of DOX of both DOX-OSC and DOX-INJ decreased rapidly in blood after iv administration. While free DOX levels in blood at 12-96 h were not detectable for DOX-INJ, in contrast, DOX level in blood at 96 h was still found for DOX-OSC. In contrast to DOX-INJ group, DOX-OSC showed a higher targeting efficiency in the liver and spleen. The AUCs of DOX in the liver and spleen were 20.0 and 47.4 times and the MRT were 11.2 and 37.2 times, respectively. And the levels of DOX-OSC in the heart and kidney tissues were significantly reduced. And the drug distribution of DOX-OSC in the heart and kidney tissues were 17.0% and 11.4%, respectively. Hence, DOX-OSC shows an excellent drug loading capabilities and a higher targeting efficiency in the liver and spleen. That the levels of DOX-OSC in the heart and kidney tissues are significantly reduced, might improve the treatment efficacy of DOX and decrease the side effects.

Treatment of displaced intra-articular fractures of the calcaneus using a small lateral incision approach / 中华创伤骨科杂志

Objective To investigate the operative treatment of displaced intra-articular fractures of the calcaneus using a small lateral incision approach.Methods Thirty-one patients with 32 intra-articular calcaneal fractures,were treated with open reduction and internal fixation through a small lateral incision approach from October 2004 to April 2006.The skin incision was made from the distal tip of the fibula to the base of the fourth metatarsal.According to Sanders classification,there were 21 typeⅡfractures and 11 typeⅢfractures.The first change of dressing was done on the second day after operation.The residual blood clots in the wounds were cleaned as much as possible when the drainage sheet was removed.The operated foot was bandaged with pressure dressing of cotton pad.Results After an average follow-up of 10.5 months(range,3 to 18 months),no soft tissue com- plications were found,and all had acceptable reduction.The preoperative X-ray film showed that B(?)hler angle was 6.84??9.36?,Gissane angle was 106.04??12.03?.The postoperative X-ray film demonstrated that B(?)hler angle was 32.06?+6.87?,Gissane angle was 115.81??9.48?,and the difference was statistically significant(P＜0.01).According to the AOFAS evaluation system for Ankle-Hindfoot,two feet scored 60-70 points,nine feet 70-80 points,16 feet 80-90 points and five feet 90-100 points.Condusion The small lateral incision approach is a good option for management of calcaneus fractures,because it causes minimal soft tissue damage,provides excellent exposure,and leads to convenience for later removal of internal fixators and subtalar arthrodesis.