Advances in liquid-phase microextraction technology and its application in biological sample pretreatment / 药学学报

Liquid-phase microextraction is a novel pretreatment technique for biological samples developed on the basis of liquid-phase extraction technology, which is simple, rapid, economical, and environmentally friendly, and has been widely used in the analysis of biological matrix samples such as blood, urine, and saliva. In this paper, we review the basic principles of the main modes of liquid-phase microextraction techniques, i.e., single-drop microextraction, dispersive liquid-liquid microextraction, and hollow-fiber liquid-phase microextraction, and the progress of their applications in biological sample pretreatment by reviewing the literature in the past five years, with a view to providing technical support and reference for sample pretreatment in the fields of in vivo drug analysis, pharmacokinetic studies and new drug development.

Targeting histone deacetylases for cancer therapy: Trends and challenges

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

Research Progress of m6A Demethylase FTO and Its Inhibitors in Acute Myeloid Leukemia --Review / 中国实验血液学杂志

Obesity-associated protein (FTO) is an important m6A demethylase that regulates RNA methylation modification and can promote the proliferation of acute myeloid leukemia(AML) cells. FTO regulates the methylation level of AML through multiple cellular signaling pathways such as FTO/RARA/ASB2, FTO/m6A/CEBPA, and PDGFRB/ERK, and participates in the occurrence, development, treatment and prognosis of AML. At present, studies have found that a variety of inhibitors targeting FTO have shown good anti-leukemia effects, and the study of FTO will provide new ideas for the treatment of AML. This review focus on the mechanism of action of FTO in AML and the research progress of FTO inhibitors in AML.

Study on the stability of SARS-CoV-2 at different temperatures / 上海预防医学

Objective:To observe the stability of severe acute respiratory syrdrome coronavirus （SARS-CoV-2） in cell cultures at different temperatures so as to provide basic data and scientific basis for the research and control of COVID-19 epidemic. Methods:The Vero E6 cells inoculated with SARS-CoV-2. According to TCID50， SARS-CoV-2 with different dilution （10-1， 10-3， 10-5， 10-6）were stored at 37 °C， 22.5 °C， and 4 °C for one to seven days， and then infectious titer was determined by micro cytopathogenic effect assay， observing cytopathic effect （CPE）， and real-time fluorescence quantitative testing. Results:SARS-CoV-2 was stable under 4 °C. The infectivity of high concentration （10-1 dilution） under 22.5 °C for seven days gradually decreased， while lower concentration completely lost infectivity after one day. The virus lost infectivity when stored at 37 °C for more than one day. Conclusion:SARS-CoV-2 is highly stable at 4 °C， sensitive to heat， and related to virus concentration.

Research progress on the traditional Chinese medicine-pharmaceutical drug interaction mediated by the ABC transporter family / 药学学报

ABC transporters on the intestinal barrier, blood-brain barrier and on tumor cells will affect drug bioavailability, transport across the blood-brain barrier and multidrug resistance. The active ingredients of traditional Chinese medicines can affect the function and expression of ABC transporters. When combined with pharmaceuticals the potential interaction between the two can change the efficacy of the medicines. We review the ABC transporter superfamily and their distribution with regard to their relationship and interactions with traditional Chinese medicine on the intestinal barrier and the blood-brain barrier, as well as their role in tumor multidrug resistance mediated by ABC transporters. We summarize the research progress over the past five years.

Advancements in stabilization technologies for membrane protein and its application in drug screening / 药学学报

Membrane proteins are the main undertakers of biofilm function, and also the most important target group for innovative drug discovery and research. About 60% of drugs targets are membrane proteins. Due to the obvious aggregation and denaturation tendency of membrane proteins in aqueous solution, it is difficult to simulate the membrane like environment to maintain the correct conformation of membrane proteins in vitro, which results in the slower-growing research on the structure and function of membrane proteins and related ligand drugs than that of water-soluble proteins. Membrane protein stabilization technology is the premise of establishing high specificity, high sensitivity and high throughput drug screening methods for membrane protein ligands, which is of great significance. In this paper, some techniques for stable separation and purification of membrane proteins are reviewed, including detergents, artificial membranes, polymers, lentiviral particles and so on, as well as their specific applications in drug screening.

Balance and Stability for Patients with Idiopathic Normal Pressure Hydrocephalus / 中国康复理论与实践

@#Objective:To observe the features of posture control in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods:From May, 2017 to May, 2018, patients with iNPH in our hospital (<italic>n</italic> = 13) and healthy controls (<italic>n</italic> = 15) were measured with sensory organization test on Balance Manager. The balance scores and strategy scores under six conditions were recorded and the comprehensive balance scores were calculated. Results:The balance scores decreased in the patients in the conditions of eyes-open/stable-support, eyes-close/stable-support, eyes-close/unstable-support and eyes-disturb/unstable-support compared with those of the controls (|<italic>Z</italic>| > 2.042, <italic>P</italic> < 0.05), as well as the comprehensive balance scores (<italic>Z</italic> = -3.617, <italic>P</italic> < 0.001); while the strategy scores increased in the conditions of eyes-close/stable-support, eyes-open/unstable-support, eyes-close/unstable-support and eyes-disturb/unstable-support (|<italic>Z</italic>| > 2.333, <italic>P</italic> < 0.05). Conclusion:There are balance disorders in the patients with iNPH, mainly associating with the disorders of proprioceptive and vestibular senses, and application of hip strategy.

Efficacy of Yangyin Yiqi Huoxue Granule () in Treatment of Ischemic Stroke Patients with Qi-Yin Deficiency and Blood Stasis Syndrome: A Randomized, Double-Blind, Multicenter, Phase-2 Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Yangyin Yiqi Huoxue Granule (, YYHG) in the treatment of ischemic stroke (IS) patients with qi-yin deficiency and blood stasis syndrome (QYDBSS), and to explore its effective dosage.@*METHODS@#The total of 288 patients were randomly assigned to the YYHG high-dose, YYHG low-dose, positive control (administered Xiaoshuantong Granule, XSTG, ), or placebo control (administered inert granule) groups (72 cases per group) by software-drived competitive block randomization. The trial was conducted for a 28-day period, with a 180-day follow-up period. The primary outcome was the comprehensive curative evaluation, and secondary outcomes were the National Institute of Health Stroke Scale (NIHSS) score, Barthel activities of daily living (ADL) index score, the quality of life index (QLI) score, and the Chinese medicine syndrome (CMS) score. All analyses were done on an intention-to-treat basis. The clinical safety was also assessed.@*RESULTS@#The total of 288 participants were recruited between June 1, 2008 and September 30, 2009, and 287 patients received intervention; the treatment groups were well balanced at baseline. The comprehensive cure rates of YYHG high-dose, low-dose, positive and placebo control groups were 63.38%, 31.94%, 36.11% and 6.14%, respectively; there was a statistical difference between the two groups (P<0.01), while the high-dose YYHG treatment group was significantly higher than the other 3 groups (P<0.01). The improvement of NIHSS, ADL, QLI and CMS scores of the YYHG high-dose and low-dose groups was significantly better than that of the positive control group and the placebo control group (P<0.05). In terms of improving the classification of the NIHSS scale and the assessment of the ADL scale, the YYHG high-dose group was significantly better than the other three groups (P<0.05), and the YYHG low-dose group was better than the placebo control group (P<0.01). At the same time, except for the QLI score, the high-dose group was better than the low-dose group (P<0.05). In terms of safety, adverse reactions after YYHG treatment were generally mild (3.78%), and no serious adverse reactions have been reported.@*CONCLUSION@#YYHG is safe and effective in the treatment of IS patients with QYDBSS.

Drug resistence and NA gene characteristics of influenza virus A/H1N1(pdm09) studied in Shanghai during 2018-2019 / 上海预防医学

Objective A/H1N1(pdm09) viruses were the dominant strains in Shanghai during 2018-2019 influenza surveillance year.This study is to provide a scientific reference for clinical drug use by investigating the susceptibility of A/H1N1(pdm09) viruses to neuraminidase inhibitors(NAIs). Methods Sixty strains of A/H1N1(pdm09) viruses were randomly selected for testing the susceptibility and drug resistance to Oseltamivir and Zanamivir by means of neutaminidase inhibition and neuraminidase (NA) gene sequencing. Results The 60 epidemic strains all proved to be susceptible to Oseltamivir and Zanamivir and the susceptibility was not observed to be decreased or remarkably decreased.In genetic sequencing, NA was not observed to present amino acid mutation at the key sites and auxiliary sites in catalytic activity, which confirmed the results of the phototypic detection of neuraminidase inhibition. Conclusion The subtype influenza viruses A/H1N1(pdm09) circulating in Shanghai during 2018-2019 surveillance year are still sensitive to NAIs, which provides a scientific reference for clinical use of drugs.However, we monitored only a number of strains and think that the work monitoring antiviral susceptibility should be continued with the wide use of the drugs.

Analysis of the inter-and intra-fraction setup errors and residual errors during stereotactic radiotherapy for brain metastasis / 中华放射肿瘤学杂志

Objective To evaluate the necessity of arc by arc setup verification in patients with brain metastases receiving stereotactic radiotherapy (SRT) by analyzing the inter-and intra-fraction setup errors and residual errors collected from the ExacTrac X-ray portal image.Methods Clinical data of brain metastases patients treated with SRT in the previous two years were retrospectively analyzed.The ExacTrac X-ray setup images were collected after the normal setup procedure.Setup errors were calculated by registering the cranial bony structures of the ExacTrac X-ray setup images to that of the digitally reconstructed setup images.The inter-and intra-fraction setup errors and residual errors were statistically analyzed.Results Seventy-five patients from 116 lesions received 337 cycles of SRT of the head.The inter-and intra-fraction translational setup errors in the x,y and z directions were (0.93±0.86) mm and (0.15±0.59) mm;(1.83± 1.27) mm and (0.25±0.73) mm;(0.96±0.80) mm and (0.14±0.56) mm,respectively.The inter-and intra-fraction rotational setup errors in the x,y,z directions were (0.65°± 0.62°) and (0.19°± 0.40°);(0.97°±0.94°) and (0.13°± 0.25°);(0.92°± 0.71°) and (0.10°± 0.29°),respectively.The residual translational setup errors in the x,y,z directions were (0.06±0.23) mm,(0.08±0.24) mm and (0.08±0.22)mm,and (0.12°± 0.27°),(0.09°± 0.18°) and (0.06°± 0.19°) for the residual rotational setup errors,respectively.For a reference setup error threshold of 0.7 mm/0.7°,99.1％ of the SRT exceeded the threshold and required setup correction.For 1 006 non-coplanar arcs,rotating the treatment couch from 0° to the treatment angle made 66.4％ of arcs exceed the threshold and require at least once setup correction.Conclusions During SRT for brain metastasis,the inter-and intra-fraction setup errors should be emphasized.It is necessary to perform arc by arc setup error verification.

Analysis of the setup errors and residual errors for ExacTrac X-ray image-guidance system for radiotherapy of somal tumors / 中华放射医学与防护杂志

Objective To retrospectively analyze the setup error in radiotherapy of somal tumors and body metastases using the ExacTrac X-ray portal image,and to evaluate the feasibility and effectiveness of 6D setup error correction in body radiotherapy.Methods The translational and rotational setup errors were calculated by registering the bony structures on the ExacTrac X-setup images to that of the digitally reconstructed setup images,and the corresponding residual errors were calculated together.Results The translational and rotational setup errors in the x (left-right),y (superior-inferior),z (anterior-posterior) and Rx (sagittal),Ry (transverse),Rz (coronal) directions were(2.27±2.02) mm,(4.49±2.52) mm,(2.27± 1.37) mm and (1.02 ± 0.73) °,(0.67 ± 0.68) °,(0.76 ± 0.84) °,respectively.The residual translational and rotational setup errors in the x(r),y(r),z(r) and Rx(r),Ry(r),Rz(r) directions were(0.27±0.48)mm,(0.37±0.45)mm,(0.22±0.30)mm and (0.17±0.33)°,(0.14±0.34)°,(0.16± 0.28) ° respectively.Conclusions Besides the translational setup errors,a certain amount of rotational setup errors exist in radiotherapy of somal tumors and body metastases.By using the 6D setup error correction of the ExacTrac system,a translational less than 0.4 mm and rotational setup errors less than 0.2° could be achieved.

Application of benzoxaboroles compounds in medicinal chemistry / 药学学报

Benzoxaborole is a series of compounds with five member ring and boron atom. Since the approval of crisaborole and tavaborole by FDA, benzoxaborole gained lots of research interests and become widely used in current drug discovery. Specially, benzoxaborole derivatives were found to exhibit anti-bacterial, anti-fungal, anti-protozoal, anti-tumor and anti-inflammatory activities. Here, we will review the properties of benzoxaborole, structure activity relationships as well as the recent progress in the biological activity of benzoxaborole derivatives.

The effect of procyanidin on periprosthetic osteolysis caused by TCP wear particles in the mouse calvaria and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the protective effects of procyanidin on periprosthetic osteolysis caused by tricalcium phosphate (TCP) wear particles in the mouse calvaria and its mechanism.@*METHODS@#Forty-eight male ICR mice were randomly divided into sham group, TCP group, and procyanidin (0.2 mg/kg, 1 mg/kg, 5 mg/kg)-treated group (n=12). A periprosthetic osteolysis model in the mouse calvaria was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2 day post-operation, procyanidin (1 mg/kg, 5 mg/kg) was locally injected to the calvaria under the periosteum every other day. After 2 weeks, all the mice were sacrificed to collect the blood samples and the calvaria. Periprosthetic osteolysis and osteoclastogenesis in the mouse calvaria were observed by tartrate resistant acid phosphatase (TRAP) staining and HE staining. mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 in the periprosthestic bone tissue were examined by real-time fluorescence quantitative PCR. Serum contents of total anti-oxidation capacity (T-AOC) and MDA, and superoxide dismutase (SOD) activity were determined by chemical colorimetry. Protein expressions of autophagic biomarkers such as Beclin-1 and LC-3 in periprosthetic bone tissue of the calvaria were examined by Western blot.@*RESULTS@#Compared with sham group, periprosthetic osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1, and serum MDA content were increased significantly in the TCP group (P＜0.05), whereas serum T-AOC level and SOD activity were decreased. The protein expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were both up-regulated markedly in the mouse calvaria of TCP group (P＜0.05). Compared with TCP group, osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 and serum MDA content were decreased obviously in the procyanidine group (P＜0.05), serum T-AOC level and SOD activity were increased, the expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were down-regulated obviously in the mouse calvaria of procyanidin group (P＜0.05).@*CONCLUSION@#Procyanidin has a protective effect of periprosthetic osteolysis caused by TCP wear particles in the mouse calvaia, its mechanism may be mediated by inhibition of oxidative stress and autophagy.

The role of blood brain barrier in postoperative cognitive dysfunction of elderly mice / 复旦学报（医学版）

Objective To observe the changes of learning and memory ability in aged mice after appendectomy or isoflurane exposure and the permeability of blood brain barrier (BBB) in hippocampus in order to find the reasons for the destruction of BBB damgge.Methods Thirty C57BL mice (18-month) were randomly divided into 3 groups:control group (group C),surgery group (group S) and inhalation group (group Ⅰ).The permeability of BBB in hippocampus was detected with Evans-blue (EB) quantification.The alterations of tight junction protein were measured by occludin and claudin-5 using Western blot on the same day.The changes of two matrix metalloproteinases MMP-2 and MMP-9 were detected.Results Compared with the control group and inhalation group,surgery group had longer escape latencies and less platform crossings,and EB leaked into the hippocampus.The expression of occludin decreased,while the expressions of MMP-2 and MMP-9 increased.Conclusions MMP-2 and MMP-9 may cause the decrease of the expression of tight junction occludin protein,and lead to the destruction of BBB,which resultes in postoperative cognitive dysfunction.

Clinical value of different detection methods in blunt ocular trauma / 国际眼科杂志(Guoji Yanke Zazhi)

Blunt ocular can cause persistent change of eye structure and function, the method of detection which is closely related to eye injury including B - can ultrasonography, UBM, OCT, FFA, scanning laser polarimetry, fundus autofluorescence, each examination with particular emphasis. This paper aims to review the advantages and disadvantages of different inspection methods in order to provide reference for clinical diagnosis and treatment of blunt ocular trauma.

Protective effect and mechanism of total anthraquinone extract of Rhei Radix et Rhizoma on cerebral ischemia-reperfusion injury / 中成药

AIM To investigate the effect and mechanism of total anthraquinone extract of Rhei Radix et Rhizoma on cerebral ischemia-reperfusion injury and to provide relevant data references for its promising use in the management of cerebral ischemia-reperfusion injury.METHODS SD rats randomly assigned to model group,sham operation group,nimodipine group,total anthraquinone extract groups (high,medium and low dose),8 in each group,were orally administered with corresponding drugs daily for a week,with rats of the model group and sham operation group given the same volume of normal saline before the models established by middle cerebral artery occlusion (MCAO).MCAO started thirty minutes after final oral administration,and the induced ischemia went on for 1.5 h for a further reperfusion,24 h after which the neurological function score,brain index,brain water content and cerebral infarct volume were measured.Elisa kits were used to detect superoxide dismutase (SOD),Malondialdehyde (MDA),Nitric oxide (NO),interleukin-1 β (IL-1β),tumor necrosis factor (TNF),interleukin-6 (IL-6).RESULTS The total anthraquinone extract of Rhei Radix et Rhizoma significantly improved the neurological function score,decreased the brain index,brain water content,reduced the cerebral infarct volume (P ＜ 0.05),increased the activity of SOD in brain tissue (P ＜ 0.01),and reduced the levels of MDA and NO in brain tissue (P ＜0.01),and the levels of IL-6,TNF and IL-1β in serum (P ＜0.01) as well.CONCLUSION The obviously protective effect on rats' cerebral ischemia-reperfusion injury by total anthraquinone extract of Rhei Radix et Rhizoma may contribute to its inhibition of inflammatory response,and its existence as an antioxidant as well.

Bcl-2: research progress from target to launched drug / 药学学报

Apoptosis is an important self-stabilizing mechanism of multicellular organisms, which plays a vital role in the development of normal living organisms and the maintenance of tissue homeostasis. The abnormalities in apoptosis often lead to body lesions including tumors. Studies have shown that Bcl-2 protein with anti-apoptosis activity is an important target in the treatment of cancer. After nearly two decades of efforts, many small molecule Bcl-2 inhibitors have been discovered to induce cell apoptosis. The small-molecule Bcl-2 inhibitor, venetoclax, was developed based on fragment-based drug design strategy and approved by the FDA in 2016 for clinical application. This agent is the first approved small-molecule drug inhibiting Bcl-2 through protein-protein interaction to induce cell apoptosis. The achievement of venetoclax benefits from a combination of drug discovery technologies and represents a milestone in the history of drug discovery. In this review we will introduce the current progress in Bcl-2 inhibitors.

Expression of Wnt5b in patients with HBV-related hepatocellular carcinoma and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of Wnt5b in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues and its correlation with the clinicopathological parameters.</p><p><b>METHODS</b>Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were employed to measure Wnt5b mRNA and protein expressions in two groups of HBV-related HCC patients (100 cases in each) selected from a cohort of 289 cases with HBV-related HCC using simple random sampling method. The correlation of Wnt5b expression with the clinicopathological parameters and the prognosis of HCC patients was analyzed.</p><p><b>RESULTS</b>Wnt5b mRNA expression was significantly higher in HCC tissues than that of adjacent noncancerous tissues in 65.0% (65/100) of the cases, and the positivity rate of Wnt5b protein was significantly higher in HCC tissues than that of adjacent noncancerous tissues (58.0% vs 22.0%, P<0.05). Wnt5b expression was significantly correlated with the tumor size (P<0.05), tumor number (P<0.01, only at the protein level), tumor differentiation (P<0.01, only at the protein level), TNM stage (P<0.05), BCLC stage (P<0.05), metastasis (P<0.05) and recurrence (P<0.01). The patients with up-regulated Wnt5b mRNA and protein had a shorter relapse-free survival (P<0.01).</p><p><b>CONCLUSION</b>s Up-regulated Wnt5b might contribute to the progression of HBV-related HCC and predicts a poor prognosis.</p>

Retraction notice to: Myosin VI contributes to malignant proliferation of human glioma cells

The Editors of Korean J Physiol Pharmacol have informed that this article may include the results of experiments that were not performed by the authors. All authors have agreed that retraction from the literature is the best corrective action to the scientific community, and apologize to the Editors and readership of Korean J Physiol Pharmacol.