Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Evaluation of inhibitory effect of tumor vaccine in colon carcinoma model mice / 中国生物制品学杂志

Objective@#To evaluate the inhibitory effect of tumor vaccines in colon carcinoma model mice.@*Methods@# Mouse bone marrow⁃derived dendritic cells（BMDCs）were stimulated by using CpG β⁃glucan nanoparticles（CNP）in vitro. The BMDCs were divided into PBS group，NP group（without CpG nanoparticles），Lysate group（MC38 cell lysate）and CpG group（CpG1826），which were determined for the expression of marker molecules on the surface by flow cytometry and for the contents of interleukin⁃6（IL⁃6）and IL⁃12p40 in the culture supernatant by ELISA. The tumor lysate nano⁃vaccine was pre⁃ pared by mixing 50 mg／mL tumor lysate（MC38 cell lysate）with 200 mg／mL CNP in a volume ratio of 1∶1，with which mice were subcutaneously immunized as Vaccine group. Vaccine group，PBS group，CNP group and Lysate group were im⁃ munized once a week，for three times in total. Mice were subcutaneously inoculated with MC38 cells，2 × 105 cells for each， in the right lower limb 1 h after the last immunization，and measured for tumor volume once every three days to plot the tumor growth curve. The ratios of CD3+ CD4+ T and CD3+ CD8+ T cells in the blood were analyzed by flow cytometry and the levels of tumor necrosis factor⁃α（TNF⁃α）and interferon γ（IFNγ）in the blood and spleen of mice were determined by ELISA.@*Results@# CNP effectively increased the expression of CD11c+ CD80+，CD11c+ CD86+，CD11c+ MHC⁃Ⅱ+ and the secretion of IL⁃6 and IL⁃12p40 in BMDCs in vitro，which were significantly higher than those in other 4 groups（t = 4. 3 ~ 46. 2，each P < 0. 05）. Compared with that of the other three groups，the tumor volume of mice in Vaccine group decreased significantly（t =2.6~3.4，eachP <0. 05）；TherewasnosignificantdifferenceinCD3+ CD8+ TandCD3+ CD8+ Tcellratios（t = 0.5~ 1. 9，each P > 0. 05）；The content of IFNγ in blood increased significantly（t = 3. 8 ~ 4. 6，P < 0. 05），while thatof TNF⁃α showed no significant difference（t = 0. 4 ~ 2. 0，each P > 0. 05）；However，the contents of IFN γ and TNF⁃α in spleen increased significantly（t = 6. 3 ~ 13. 0，each P < 0. 001）.@*Conclusion@#The prepared nano⁃vaccine of tumor lysate improvedtheimmune level in mice and effectively inhibited the growth of colon carcinoma.

Prenatal ultrasound diagnosis of fetal right aortic arch / 中国医师进修杂志

Objective:To explore the prenatal ultrasound manifestations of fetal congenital right aortic arch and its diagnostic significance.Methods:The characteristics of prenatal ultrasound images (focusing on the three vessel trachea section) and clinical data of 128 cases of fetal congenital right aortic arch diagnosed in Dalian Women and Children′s Medical Center(Group) from January 2014 to January 2019 were analyzed retrospectively.Results:Among 128 cases of fetal congenital right aortic arch, 111 cases were right aortic arch and leftductus arteriosus with aberrant left subclavian artery (RAA-LDA-ALSA), 1 case was diagnosed as left aortic arch atresia of double aortic arch by operation after birth; 9 cases were right aortic arch and right ductus arteriosus (RAA-RDA); 6 cases were mirror-image right active aortic arch and left ductus arteriosus connected to descending aorta (RAA-BAMB-LDA-DAO); 2 cases were mirror-image right aortic arch and left ductus arteriosus connected to the left innominate artery (RAA-BAMB-LDA-LINA). The three vessels and trachea view (3VT) had characteristic sonographic features.If necessary, coronary section of the upper thoracic aorta and / or stic were added - HD live flow technology assisted the diagnosis of 3vt section.Conclusions:Three vessel trachea view is a sensitive and effective view for prenatal detection and diagnosis of congenital right aortic arch. Upper thoracic aorta coronal section and combined stic - HD live flow technology can make up for its shortcomings. Prenatal ultrasound diagnosis of right aortic arch hasguiding significance for prenatal prognosis consultation.

Role of dexamethasone/captopril co-loaded immunoliposome-nanoparticle hybrids on the regulation of macrophage polarization in mice with glomerulonephritis / 药学学报

In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.

Development and research of compound caffeine waterless swallowed granules based on reverse engineering / 药学学报

In this study, the reverse engineering technology was used to analyze the prescription and process of Doppelherz® Energy DIRECT, based on the composition of the prescription on the official website of the product, the detection method of composition is established according to the pharmacopoeia and literature information, combined with gravimetric analysis to complete prescription analysis. The prescription composition of the reference listed drug was determined to be composed of caffeine, taurine, vitamin B, anhydrous glucose, citric acid, sorbitol, sucralose, magnesium salts of fatty acids, in which the glucose content was 71.4%, the citric acid content was 7.0% and the magnesium salts of fatty acids content was < 5.8%. According to patent inquiry, Raman imaging and other technologies, the preparation process of the marketed preparation has been basically obtained, and the development of the self-made preparation has been completed on this basis. The study was approved by the Ethics Committee of the Academy of Military Medical Sciences. Combined with the results of the taste evaluation experiment and the caffeine dissolution test of the preparation in 1 min, the hot-melt extrusion technology was screened out as the taste-masking technology of the self-made preparation, the parameters of the hot-melt extrusion process were screened by differential scanning calorimetry analysis, and finally a product with good taste and qualified quality was obtained, which provided a reference method for the research and development of related preparations.

Preparation of nanocapsules of active ingredients of Garcinia hanburyi and evaluation of their antidiabetic activity / 中国药房

OBJECTIVE To prepare Gambogic acid （GA） nanocapsules （GA-LNCs） and Neogambogic acid （NGA） nanocapsules（NGA-LNCs），and to evaluate their antidiabetic activities. METHODS Using water as the aqueous phase ，medium- chain triglyceride as the oil phase and polyethylene glycol monostearate as the surfactant ，GA-LNCs and NGA-LNCs were prepared by phase inversion method. Using entrapment efficiency and drug-loading amount as index ，the formulation technologies of above 2 nanocapsules were optimized by simplex lattice design. Its physical and chemical properties were investigated. The diabetic mice model was established. GA-LNCs and NGA-LNCs （1.92 and 2.42 mg/kg respectively ）were given intragastrically ，once a day ，for consecutive 6 weeks. The fasting blood glucose of mice ，the activities of superoxide dismutase （SOD）and glutathione peroxidase （GSH-Px），the contents of malondialdehyde （MDA），total cholesterol （TC），triglyceride （TG），high-density lipoprotein cholesterol（HDL-C）and low-density lipoprotein cholesterol （LDL-C）were all detected. RESULTS The optimal formulation of 2 kinds of nanocapsules included 60％ water，10％ medium-chain triglyceride ，30％ polyethylene glycol monostearate （total amount of the three was 2 g）and 35 mg GA or NGA . The encapsulation efficiencies of GA-LNCs and NGA-LNC obtained by the optimal formulation were （92.01±0.68）％ and（93.12±2.11）％；the drug-loading amount were （0.99±0.21）％ and（1.21±0.22）％， respectively. GA-LNCs and NGA-LNCs were yellow ，homogeneous and transparent liquid without precipitation. They were spherical in microscopic shape ， and had obvious shell- Δ 基金项目：吉林省科技发展计划项目（No.20200404090YY）；吉 membrane structure. The particle sizes were （28.11 ± 9.76） 林省教育厅科学技术研究项目（No.JJKH20210372KJ） ＊硕士研究生 。研究方向 ：植物药 。E-mail：zhanhe0108@163. and（22.06±6.84）nm；Zeta potential were （－4.09±1.00） com and（－17.40±1.32）mV，and polydispersity were 0.93±0.06 # 通信作者：讲师，博士。研究方向：中药有效成分治疗疾病的作 and 0.74±0.12. The results of animal experiments showed that 用机制。E-mail：chenweijia_jlau@163.com both GA-LNCs and NGA-LNCs could sig nificantly increase 中国药房 2022年第33卷第9期 China Pharmacy 2022Vol. 33 No. 9 ·1075· the activities of SOD and GSH-Px and the seru m content of HDL-C （P＜0.05 or P＜0.01）in model mice ，and significantly decreased the fasting blood glucose and the serum contents of MDA ， TC， TG and LDL-C （P＜0.05 or P＜0.01）. CONCLUSIONS GA-LNCs，NGA-LNCs prepared in this study are good in physical and chemical properties and have good anti-diabetes activity.

Meta-analysis of efficacy and safety of Suhuang Zhike Capsules in treatment of chronic obstructive pulmonary disease / 中国中药杂志

This study aims to evaluate the effectiveness and safety of Suhuang Zhike Capsules in treating chronic obstructive pulmonary disease. The Chinese and English databases were searched(from the establishment to July 2021) for randomized controlled trials(RCTs) on the treatment of chronic obstructive pulmonary disease with Suhuang Zhike Capsules, yielding 130 articles and finally 12 eligible RCTs. The 12 RCTs enrolled a total of 1 159 patients(579 in experimental group, 580 in control group), with 728 males(62.8%) and 431 females(37.2%). Meta-analysis showed that the conventional western medicine combined with Suhuang Zhike Capsules increased clinical efficacy(OR=4.31, 95%CI[2.88, 6.46], Z=7.08, P<0.000 01), forced expiratory volume in one second(FEV1)(SMD=0.88, 95%CI[0.60, 1.16], Z=6.24, P<0.000 01), forced vital capacity(FVC)(SMD=0.96, 95%CI[0.38, 1.55], Z=3.22, P=0.001), forced vital capacity rate of one second(FEV1/FVC%)(SMD=0.85, 95%CI[0.51, 1.19], Z=4.92, P<0.000 01), and maximum voluntary ventilation(MVV)(SMD=0.61, 95%CI[0.39, 0.83], Z=5.40, P<0.000 01) compared with the conventional western medicine alone. The differences in residual volume/total lung capacity(RV/TLC)(SMD=-0.93, 95%CI[-3.38, 1.53], Z=0.74, P=0.46) and adverse reactions(OR=1.39, 95%CI[0.76, 2.56], Z=1.07, P=0.28) are insignificant. The study showed that the conventional western medicine combined with Suhuang Zhike Capsules could improve clinical efficacy and lung functions in the treatment of chronic obstructive pulmonary disease. In addition, the combination had been verified to be safe. However, in view of the uneven method quality, small sample size, and inconsistent outcome indicators of the included studies, higher-quality, multi-center, and large-sample RCTs are needed for further verification.

Clinical analysis of 10 patients of pregnancy with cervical cancer / 中国医师进修杂志

Objective:To analyze the clinical features, diagnosis and treatment plan, clinical outcomes of pregnancy with cervical cancer.Methods:The clinical data of 10 pregnant women with cervical cancer from January 2008 to October 2018 in Dalian Obstetrics and Gynecology Hospital Affiliated to Dalian Medical University, the First Hospital of Dalian Medical University, Dalian Central Hospital, Dalian Women and Children′s Medical Center and Wafangdian Central Hospital of Liaoning Province were retrospectively analyzed.Results:The incidence of pregnancy with cervical cancer was 0.004% (10/238 128). Among the 10 cases of pregnancy with cervical cancer, the gestational weeks ≤ 20 weeks at the time of diagnosis was in 6 cases, and they all chose to terminate the pregnancy; the gestational weeks 20 +1 to 30 weeks at the time of diagnosis was in 1 case, and the patient chose to terminate the pregnancy; the gestational weeks >30 weeks at the time of diagnosis was in 2 cases, and they all chose to continue the pregnancy; 1 case was diagnosed after delivery. There were 3 newborns, including 1 premature infants, and they all survived. Conclusions:It is helpful to the diagnose of the disease to strengthen cervical cancer screening before pregnancy and improve the examination of patients with abnormal symptoms during pregnancy. The treatment plan should be individualized according to the pregnancy status, stage of the disease, and wishes of the patient and family.

Effect of Danggui Shaoyaosan on TLR4/MyD88/JNK Signaling Pathway on Rats with Nonalcoholic Fatty Liver Disease / 中国实验方剂学杂志

Objective:To explore<italic> </italic>the efficacy and mechanism of Danggui Shaoyaosan on rats of nonalcoholic fatty liver disease （NAFLD）. Method:Sixrty SPF SD male rats were randomly divided into normal group， model group，essentiale （0.144 g·kg^-1） and low， middle and high-dose of Danggui Shaoyaosan groups （2.44， 4.88， 9.76 g·kg^-1）. High fat diet were fed to bulid the NAFLD model， and each treatment group was given corresponding drugs at the same time. After 8 weeks， the serum and liver tissue were collected to detect the contents or activities of total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartic acid aminotransferase （AST）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and interleukin-10 （IL-10） in serum， the contents of TC， TG and free fatty acid （FFA） in liver tissue， Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to observe the gene and protein expressions of Toll-like receptor 4 （TLR4）， myeloid different factory 88 （MyD88） and c-Jun n-terminal kinase （JNK） and the protein expression of phosphorylation JNK（p-JNK） in liver tissue. Hematoxylin-eosin （HE） staining and Oil red staining to observe the pathological morphological changes of liver. Result:Compared with control group， the contents or activities of TC， TG， ALT， AST and TNF-<italic>α</italic> in serum， the contents of TC， TG and FFA in liver and the gene and protein expressions of TLR4， MyD88， JNK， and the protein expression of p-JNK in liver tissue of model group were distinctly increased （<italic>P</italic><0.01）， the content of IL-10 was significantly decreased （<italic>P</italic><0.01）. Compared with model group， the contents or activities of TC， TG， ALT， AST and TNF-<italic>α</italic> in serum， the contents of TC， TG and FFA in liver and the mRNA and protein expressions of TLR4， MyD88 and JNK， and the protein expression of p-JNK in liver tissue of Danggui Shaoyaosan groups were significantly reduced （<italic>P</italic><0.05，<italic>P</italic><0.01）， the content of IL-10 in serum of Danggui Shaoyaosan groups was distinctly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）， HE staining and Oil red staining show that the degree of liver steatosis was alleviated obviously by Danggui Shaoyaosan. Conclusion:Danggui Shaoyaosan has a better treatment on NAFLD by inhibiting TLR4/MyD88/JNK pathway and alleviating the inflammation response.

Full-factor design of experiment application in the development of printing ink for binder jetting 3D printed preparation / 药学学报

The development of printing ink is a challenge for binder jetting 3D printed preparations, which directly determines the quality of the printed product. This study adopted a 23 full-factor Design of Experiment (DoE) with three central points to optimize the printing ink composition of levetiracetam 3D printed dispersible tablet based on the concept of Quality by Design. Firstly, using polyvinyl pyrrolidone K30, glycerin and polysorbate 20 as independent variables based on 40% (v/v) isopropanol aqueous solution, and weight variation, hardness, friability and dispersion uniformity of the printed tablets were used as dependent variables. Then obtained the design space of the printing ink prescription by DoE model analysis, and the response optimizer was used to obtain the optimal printing ink prescription: isopropanol aqueous solution containing 0.1% (w/w) polyvinyl pyrrolidone K30 and 4.0% (w/w) glycerin. The jetting mechanism and wettability of the printing ink were analyzed, and different strengths of personalized 3D printed tablets were prepared and characterized, which verified the rationality of the printing ink formulation. This study provided a reference for the development of printing ink for binder jetting 3D printed preparations.

Optimization of process parameters of 3D printed clozapine dispersive tablets and establishment of personalized dose model / 药学学报

This study aims to establish the design space of the key processes for drop-on-powder 3D printing based on design of experiment (DoE). By utilizing Minitab, an experimental scheme with three factors, two levels and three center points was designed to analyze the factors that significantly affected the tablet quality attributes. Furthermore, the factor interactions were analyzed using Minitab. subsequently, the computer aided drafting (CAD) software was used to adjust the model volume with fixed radius/height ratio (r/h = 1.25) and establish a linear regression equation between model volume and dose. As a result, the drug dose could be controlled in a flexible manner. The finally determined process parameters were: ink-jet level is 12, layer thickness is 150 μm, and the X-axis printing head speed of 635 mm·s-1. Regression equation between drug content (y) and model volume (x) was y = 0.062 x - 0.582 7 (R2 = 0.999 9) showing good linear relationship. This indicated that robust and feasible process parameters were obtained through DoE, and the preparation of personalized-dose tablets was realized with good reproducibility.

Circadian rhythm abnormality and time therapy of bipolar disorder / 中华行为医学与脑科学杂志

Bipolar disorder is a common, highly disabling psychiatric disorder characterized by early onset, frequent episodes, high suicide risk, and chronic outcomes, and is associated with severe social dysfunction. The pathogenesis of bipolar disorder is still unclear, and current studies mainly focus on circadian rhythm abnormalities, including rhythm gene mutation, polymorphism, abnormal kinase expression, and rhythm abnormalities in neurotransmitter secretion and transport. It has been found that at any stage of bipolar disorder, whether prodrome, episode, or remission, patients exhibit circadian rhythm disruptions, including disrupted sleep-wake cycles, hormonal phase abnormalities, and irregular social rhythms. Based on this mechanism, the time therapy, such as light therapy, dark therapy, sleep deprivation and behavioral intervention, can rapidly improve the circadian rhythm of patients with bipolar disorder, achieve the goal of rapid relief of symptoms, with fewer side effects, low risk of switching to manic. In this paper, circadian rhythm mechanism, clinical manifestations and chronotherapy of bipolar disorder are reviewed to provide a basis for clinical diagnosis and treatment.

Predictive performance of Smart Dose, PharmVan and JPKD on Vancomycin plasma concentration / 中华危重病急救医学

Objective:To evaluate the predictive performance of the individualized drug delivery decision-making system including Smart Dose, PharmVan and JPKD on predicting the Vancomycin plasma concentration and to analyze the related factors affecting the predictive performance.Methods:The clinical data of patients who were treated with Vancomycin and received therapeutic drug monitoring (TDM) admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to July 2020 were retrospectively collected. Smart Dose and PharmVan were used to predict the plasma concentration of Vancomycin of the initial regimen. Smart Dose, PharmVan and JPKD were used to predict the plasma concentration of Vancomycin of the adjustment regimen for patients whose initial steady-state trough concentration were not qualified. The relative predictive error (PE) between the measured plasma concentration and predicted plasma concentration was calculated and box plotted. Mann-Whitney U test was used to evaluate the difference of the absolute value of PE (APE) predicted by each software for Vancomycin plasma concentration. The TDM results were divided into accurate prediction group (APE < 30%) and the inaccurate prediction group (APE≥30%) according to the APE value. Patients and disease characteristics including gender, age, body weight complication, Vancomycin medication and TDM results were collected from electronic medical records. Univariate analysis and multivariate Logistic regression analysis were used to screen the related factors that influence the predictive performance of Smart Dose, PharmVan and JPKD; and receiver operating characteristic curve (ROC curve) was drawn to evaluate its predictive value. Results:A total of 185 patients were enrolled, and 258 plasma concentration of Vancomycin were collected, including 185 concentrations of initial regimen and 73 concentration of adjustment regimen. There was no significant difference in the APE of the initial regimen of plasma concentration between Smart Dose and PharmVan. No significant difference in the APE of the adjustment regimen of plasma concentration was found among Smart Dose, PharmVan and JPKD. The accuracy of Smart Dose in predicting the plasma concentration of the adjustment regimen was better than that of the initial regimen [22.94% (10.50%, 36.24%) vs. 29.33% (13.07%, 47.99%), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of initial regimen showed that the proportion of patients with hypertension in the accurate prediction group was significantly higher than that in the inaccurate prediction group [43.3% (42/97) vs. 27.3% (24/88), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of adjustment regimen showed that the proportion of patients with valvular heart disease in the accurate prediction group was significantly lower than that in the inaccurate prediction group [23.4% (11/47) vs. 46.2% (12/26), P < 0.05]. The univariate analysis of factors affecting the performance of JPKD in predicting the concentration of adjustment regimen showed that the body weight of patients in the accurate prediction group was significantly higher than that in the inaccurate prediction group (kg: 62.8±14.9 vs. 54.8±12.8, P < 0.05). Multivariate Logistic regression analysis indicated that hypertension was a beneficial factor for Smart Dose to predict the initial plasma concentration of Vancomycin [odds ratio ( OR) = 0.526, 95% confidence interval (95% CI) was 0.281-0.983, P = 0.044], and low body weight was an independent risk factor for the inaccurate prediction of JPKD for adjustment regimen ( OR = 1.042, 95% CI was 1.001-1.085 , P = 0.043). ROC curve analysis indicated that the area underROC curve (AUC) of the body weight for evaluating the accuracy of JPKD in predicting Vancomycin plasma concentration was 0.663, and 95% CI was 0.529-0.796 ( P = 0.023). When the body weight was less than 55.95 kg, the risk of inaccurate prediction of JPKD in predicting Vancomycin plasma concentration was increased, and the predictive sensitivityand specificity were 75% and 60% respectively. Conclusions:There is no significant difference in the predictive performance of Smart Dose, PharmVan or JPKD on Vancomycin plasma concentration. Smart Dose had a better predictive performance for the Vancomycin plasma concentration of adjustment regimen than initial regimen. Smart Dose had a better predictive performance when the patient was concomitant with hypertension. JPKD had a poor predictive performance for low-body weight patients. The predictive performance of JPKD was decreased when the body weight was lower than 55.95 kg.

Application and prospect of alkyl polyglycosides absorption enhancers in drug delivery system / 药学学报

The efficient and safe delivery of drugs to the therapeutic site through the biofilm has traditionally been a difficult and hot topic in the field of drug delivery. In recent years, alkyl polyglycoside (APG) have become ideal penetration enhancers for drug delivery systems because of their high permeability, good safety and biodegradability, which has attracted wide attention of domestic and foreign researchers. In this paper, the physical and chemical properties, characteristics, action mechanism and application of APG in drug delivery system are reviewed, and its application prospect in drug delivery system is prospected.

The principle of drop-on-powder 3D printing and its application and challenge in solid preparation / 药学学报

3D printing technology has the advantages of accurate spatial distribution, accurate drug release and personalized drug dosage, which can make up for the shortcomings of traditional pharmaceutical technology. In recent years drop-on powder (DoP) 3D printing technology has been widely used in pharmaceutical preparation. Compared with other types of 3D printing technology, it is more simple, flexible and easy to operate. In 2015, Aprecia Pharmaceuticals announced that the US Food and Drug Administration (FDA) approves the launch of its first instant tablet Spritam® (levetiracetam) made with DoP 3D printing. After the first 3D printed medicine was launched, people also saw the unique advantages and broad prospects of DoP 3D printing technology platform in pharmaceutical preparation. This review focuses on the technical principles and key factors of DoP 3D printing, its application in the preparation field and its future development challenges.

Different distributions of nerve demyelination in chronic acquired multifocal polyneuropathies / 中华医学杂志(英文版)

BACKGROUND@#Multifocal motor neuropathy (MMN), Lewis-Sumner syndrome (LSS), and many chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) are representative of acquired multifocal polyneuropathy and are characterized by conduction block (CB). This retrospective study aimed to investigate the demyelinating distribution and the selective vulnerability of MMN, LSS, and CIDP with CB (CIDP-CB) in nerves.@*METHODS@#Fifteen LSS subjects (107 nerves), 24 MMN subjects (176 nerves), and 17 CIDP-CB subjects (110 nerves) were included. Their clinical information was recorded, blood and cerebrospinal fluid tests were conducted, and nerve conductions of the median, ulnar, radial, peroneal, and tibial nerves were evaluated. CB, temporal dispersion, distal motor latency (DML), and F-wave latency were recorded, and nerve conduction velocity, terminal latency index, and modified F-wave ratio were calculated.@*RESULTS@#CB was more likely to occur around the elbow in CIDP-CB than in MMN (78.6% vs. 6.8%, P < 0.01) but less likely to occur between the wrist and the elbow than in LSS (10.7% vs. 39.3%, P < 0.05). Tibial nerve CB was most frequently observed in MMN (47.4%, P < 0.05). CIDP-CB was characterized by a prolonged DML in all nerves, and slow motor nerve velocity of the upper limb was significant when CB nerves were excluded (P < 0.05).@*CONCLUSIONS@#We report the different distributions of segmental and diffuse demyelination of the ulnar and tibial nerves in LSS, MMN, and CIDP-CB. These distinct distributions could help in differentiating among these conditions.

Trapa natans pericarp extract ameliorates hyperglycemia and hyperlipidemia in type 2 diabetic mice

Abstract The pericarp of Trapa natans L., an annual aquatic floating herb belonging to Lythraceae family, is used as a folk medicine in China. In this study, extracts of Trapa natans pericarp were tested both in vitro and in vivo through a high-fat diet with a single medium dosage streptozotocin injection induced type 2 diabetic mice. Different solvent extracts of Trapa natans pericarp showed α-amylase and α-glucosidase inhibitory activity. After four weeks administration, the ethyl acetate extract of Trapa natans pericarp (50 and 100 mg/kg b.w.) reduced fasting blood glucose level, ameliorated oral glucose tolerance and insulin resistance, improved serum lipids alterations in type 2 diabetic mice as well. Additionally, ethyl acetate extract significantly elevated the insulin receptor substrate 1 and Akt serine/threonine kinase phosphorylation compared to diabetic group. HPLC-MS and HPLC-DAD analysis showed that the ethyl acetate extract was rich in hydrolysable tannins. Results support the notion that Trapa natans pericarp extract has a potential hypoglycemic activity.

Effect of compound electrolyte injection on phosphatidylserine exposure in erythrocytes after blood salvage-retransfusion in dogs / 中华麻醉学杂志

Objective@#To evaluate the effect of compound electrolyte injection on phosphatidylserine (PS) exposure in erythrocytes after blood salvage-retransfusion in dogs.@*Methods@#Twenty healthy mongrel dogs, weighing 10-15 kg, aged 3-5 weeks, were divided into 2 groups (n=10 each) using a random number table method: normal saline group (group NS) and compound electrolyte injection group (group MEI). The process of intraoperative blood salvage-retransfusion was simulated in both groups: femoral vein was cannulated for blood withdrawal until the volume of blood lost was 400 ml, and the shed blood was salvaged by a blood recovery machine.The washing solution was normal saline in group NS and compound electrolyte injection in group MEI.The erythrocytes were retransfused after being labeled with fluorescein isothiocyanate.Blood samples were obtained before and after blood salvage for determination of erythrocyte ATP content by enzyme-linked immunosorbent assay.Blood samples were obtained at 24, 48 and 72 h after blood retransfusion, and the PS exposure rate of the salvaged erythrocytes was determined by flow cytometry.The spleen was taken at 72 h after retransfusion to detect the phagocytosis rate of salvaged erythrocytes by monocytes.@*Results@#There was no significant difference in ATP content before and after blood salvage between the two groups (P>0.05). Compared with NS group, the PS exposure rate of the salvaged erythrocytes at each time point after retransfusion and phagocytosis rate of salvaged erythrocytes by monocytes were significantly decreased in MEI group (P<0.05).@*Conclusion@#Compound electrolyte injection as a washing solution for intraoperative blood salvage can reduce the PS exposure in salvaged erythrocytes and is helpful in prolonging the lifespan of erythrocytes after retransfusion in dogs.

Study on the FBN1 gene mutation spectrum and association between genotype and clinical phenotype in 300 Marfan syndrome patients and their relatives / 中华胸心血管外科杂志

Objective To investigate the correlations between the FBN1 gene mutation types and the clinical phenotype . Methods 87 probands with Marfan or Marfan-like syndromes and their family members were enrolled in this study ( total 300 cases).The clinical manifestations of each patients involving the ocular, cardiovascular system, skeletal system and other im-plicated systems were collected and evaluated .According to the clinical manifestations , these patients were divided into two groups, namely aortic dissection group and aortic root aneurysm group.Blood samples were taken from patients and DNA se-quencing was performed on each patient by the genetic aortic disease gene Panel .The detected single nucleotide variants ( SNVs)/indel were interpreted according to the ACMG guidelines, and the pathogenic variation was confirmed through Sanger sequencing.The aortic wall tissue was obtained from MFS patients who underwent surgery .The correlations between genotypes and clinical phenotypes were further explored by comparing the aortic wall tissue histological specimens of each genotype pa-tient.Results A total of 92 FBN1 mutations(31％) were detected in 300 people with Marfan syndromes or Marfan-like syn-dromes, 18 of which were undiscovered mutations.There were 49 missense mutations(53.26％), 13 splicing mutations (14.13％), 17 frameshift mutations(18.48％), and 13 nonsense mutations(14.13％).In this cohort, 24 cases had aortic dissection and 25 cases were aortic root aneurysm.Statistical analysis revealed that patients with aortic dissection mostly ap-peared in frameshift mutations(29.17％ vs.4.00％, P =0.017).However, patients with aortic root aneurysm mostly ap-peared in missense mutations(72.00％ vs.37.50％, P =0.015), and accompanied with ectopia lentis(41.67％ vs. 8.33％, P=0.008).Pathological specimens staining found that elastic fibers in the aortic wall of patients with frameshift mu-tations are sparser, and the smooth muscle cells are more deficient and more disorganized than patients with missense muta-tions.Conclusion FBN1 gene frameshift mutations result a lack of elastic fibers and disorganized smooth muscle cells in aor-tic wall and are presented more in patients with aortic dissection than aortic root aneurysm .

Application of abdominal aortic balloon combined hemostasis in the cesarean section with invasive completeplacenta previa / 中国医师进修杂志

Objective To investigate the value of abdominal aortic balloon combined homeostasis in the cesarean section with invasive completeplacenta previa. Methods Data of 47 cases of completeplacenta previa with placenta accrete from March 2007 to August 2018 were analyzed retrospectively. Seventeen cases (study group) were treated with abdominal aortic balloon combined homeostasis before cesarean, and 30 cases (control group) did not receive balloon occlusion. The operation time, intra-operative blood loss, intra-operative blood transfusion volume, disseminated or diffuse intravascular coagulation (DIC) rate, hysterectomy rate and post operative complications, time of postoperative hospital stay were compared. Also, the blood coagulation parameters 24 h after operation, including activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer werecompared between the two groups. Results Significant difference was observed in the blood loss [1 000 (800—2 000) ml vs. 2 200 (1 000-4 100) ml, Z=-2.272, P=0.023] and blood transfusion volume [400 (0-2 450) ml vs. 2 460 (200-4 460) ml, Z =- 2.02, P = 0.03], 16 cases of the study group still bled after releasing the balloon.Fifteen cases of them received uterine artery ligation. Bleeding stopped after uterine balloon compression in 1 case. Eleven cases of the 15 cases received uterine balloon compression at the same time. One case of 28 weeks gestation underwent subtotal hysterectomy due to hemorrhagic shock combined with DIC caused by placenta accretion of the bladder. While in control group, 7 cases underwent total hysterectomy because hemorrhagic shock combined with DIC and 3 cases underwent subtotal hysterectomy due to heavy bleeding, and there was statistical significance between two groups [1/17 vs. 33.3%(10/30), P=0.039]. Conclusions Temporary balloon occlusion of the abdominal aorta combined with conventional homeostasis can reduce blood loss, blood transfusion and hysterectomy rate in the cesarean section complicated with invasive complete placenta previa.