Research progress of biomimetic nano drug delivery system in nervous system disease / 药学学报

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

Research progress of anti-tumor in situ gel delivery system / 药学学报

Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.

Brief analysis on GAO Shu-zhong's qiguan theory and its clinical application / 中国针灸

The paper introduces professor GAO Shu-zhong's experience in qiguan (umbilicus pass) theory and its clinical application. Professor GAO believes that the umbilicus is the "pass" where the primary qi of sanjiao transported from the lower jiao to the middle jiao. It is the general pivot of qi transformation of yin and yang, as well as the place for qi ascending, descending, exiting and entering in the human body. Hence, the umbilicus is called qiguan (umbilicus pass). In clinical practice, associated with observation, palpation and pulse diagnosis, the qiguan theory is conductive to disease diagnosis. Moreover, the therapeutic methods for promoting qiguan is generated, i.e. umbilicus-acupuncture therapy and umbilicus-moxibustion therapy. In the umbilicus-acupuncture therapy, Gao 's umbilicus five points (umbilicus heart, umbilicus stomach, umbilicus liver, umbilicus kidney and umbilicus lung) are commonly selected. With the umbilicus- moxibustion therapy, the isolated moxibustion with different herbal materials is exerted at the umbilicus, in which, the herbal materials with drastic medical action, pungent and fragrant in flavor and warm in property are specially selected.

Study on Electromagnetic Interference Risk of Active Implantable Medical Devices in Multiple Unit Environment / 中国医疗器械杂志

Concerning on the safety risks caused by electromagnetic interference of patients implanted with high-risk active implantable medical devices in the environment of domestic MUs, this study evaluates and focuses on the requirements of electromagnetic compatibility in domestic and international standards for rail transit vehicles, the main mechanism of risks caused by EMI, the actual measurement of environmental data in MUs and the working performance of various active implantables in the compartment. The test results shows that all kinds of active implantable medical device samples works normally in the CRH2A EMU in China, and there is still a large margin between the measured radiation emission in MU and the limit required by the standards.

Splenic tyrosine kinase promotes pulmonary angiogenesis in rats with hepatopulmonary syndrome / 生理学报

The present paper was aimed to study the role of spleen tyrosine kinase (Syk) in angiogenesis in hepatopulmonary syndrome (HPS) and the underlying mechanism. Sprague Dawley (SD) rats were randomly divided into three groups: sham operation group (sham group), common bile duct ligation (CBDL) 5-week group (5W group) and R788 intervention group (R788 group). HPS model was established by CBDL. Rats in R788 group were intraperitoneally injected with R788 (20 mg/kg) once daily to week 5 after CBDL operation. The protein expression levels and distribution of Syk, p-Erk1/2, and p-Akt in lung tissue were detected by Western blot and immunohistochemistry. Immunofluorescence staining was used to observe the location of Syk expression and the number of angiogenesis in lung tissue. The results showed that, compared with sham group, 5W group exhibited up-regulated protein expression level of Syk, increased phosphorylation levels of Erk1/2 and Akt, and increased number of pulmonary microvessels. Compared with 5W group, R788 group exhibited down-regulated protein expression level of Syk, decreased phosphorylation levels of Erk1/2 and Akt, and decreased number of pulmonary microvessels. These results suggest that Syk may promote pulmonary angiogenesis in HPS model rats by activating downstream Erk1/2 and Akt signaling pathways, which provides a theoretical basis and potential drug therapeutic targets for the clinical treatment of HPS.

Advances in research on exosomes as drug delivery vehicles / 药学学报

Exosomes are membranous vesicles that are actively secreted by cells. They can be isolated from various cell culture media and animal body fluids. Exosomes are mainly composed of lipids, proteins and nucleic acids. They have small molecular structure and high biocompatibility with size of 40-100 nm. In addition, exosomes are natural endogenous nanocarriers that can transport lipids, proteins, DNA and RNA. Studies have shown that exosomes play an important role in long-distance communication between cells, in physiological and pathological processes. This article introduces the composition and physiological functions of exosomes, and summarizes the relevant content of exosomes as drug delivery vehicles. The applications of exosomes in central nervous system diseases, especially brain diseases and tumors are summarized.

Recent advances in the drug formulations of anti-tumor antibiotics / 药学学报

Anti-tumor antibiotics exhibit great application potential in the anti-tumor therapy. Some drugs have become the first-line medication clinically. However, there are always various problems associated with anti-tumor antibiotics, such as poor solubility and instability as well as severe systemic side effects. It is important to choose suitable delivery carriers for a reasonable delivery system for a good targeting ability, enhanced anti-tumor efficacy and reduced adverse effects of the anti-tumor antibiotics, especially in the smart delivery systems. This review summarizes the carriers and the advances in the delivery systems of anti-tumor antibiotics, including anti-tumor antibiotic drugs currently on the market, in the clinical research stage and in the basic research stage.

Research on Field Strength of Radiated Immunity Test for Active Implantable Medical Devices / 中国医疗器械杂志

In order to compare the radiation immunity test level of ISO 14708 series standards and the domestic and international environmental radiation standards and then to ascertain whether the radiated immunity test level has reached the limit of the radiation strength in the relevant radiation environmental standards, this paper calculated the radiation field intensity and power density according to the radiated immunity test of ISO 14708 standards, and compared with the limit of ICNIRP 1998 and GB 8702-2014.

A Torso Simulator Design for Implantable Nerve Stimulator Test / 中国医疗器械杂志

This paper introduces ISO 14708-3:2017, the new edition of the international standard for implantable neurostimulator, and emphasizes the new requirements in the clause of protection from RF electromagnetic interference. To meet this new requirements, this paper presents a design of torso simulator for the testing of implantable neurostimulator. The design includes volume conductor, electrodes and grids, which can simulate the actual operating environment of implantable neurostimulator in RF electromagnetic interference testing. The torso simulator is verified by performance in the last part of the paper.

Analysis of the Electromagnetic Compatibility Standard for Active Implantable Medical Devices Using in the Heart / 中国医疗器械杂志

In this paper,standards for active implantable cardiac medical devices are discussed.Potential EMC risks and its correspondent tests settings as well as the design principle of the tests have been analyzed.The problems arises from the difference between domestic and international standards on the limitation of exposure of the general public to electromagnetic fields and the lack of assessment of EMC risk which generated by the the 5th generation mobile communication for the impact on the active implantable devices devices.

General gastroscopy of gastroesophageal reflux disease: Analysis of 4086 cases / 解放军医学杂志

Objective To analyze the characteristics ofgastroesophageal reflux disease (GERD) under general gastroscope.Methods The detection rates of GERD related abnormalities such as esophagitis,Barrett esophagus and hiatal hernia under the first gastroscopy of the adult GERD patients from January 2013 to January 2017 in our center and the statistical relationship between the abnormal findings were analyzed retrospectively.Results A total of 4086 GERD patients,2004 males and 2082 females,were included in this study,and the age was 18-89(50.4 ± 13.3) years old.The detection rate of non erosive GERD was 78.7％,esophagitis 21.3％;non Barrett esophagus 87.7％,suspected Barrett esophagus 8.3％,Barrett esophagus 3.9％;generally normal cardia 61.4％,short segment hiatus hernia 20.4％,and long segment hiatal hernia 18.2％.The detection rates of esophagitis showed statistically significant differences (P＜0.001) between the three groups of generally normal cardia,short segment hiatal hernia and long segment hiatal hernia;The detection rate of Barrett esophagus was significantly higher in long segment hiatal hernia group than in generally normal cardia group and short segment hiatal hernia group (P＜0.001,P=0.012),but the difference between the later two groups was not statistically significant (P＞0.013).Comparing the three age groups of 18-39,40-59 and ≥60 years old,the detection rate of hiatal hernia was significantly higher in the group of≥60 years old than in the 18-39 and 40-59 years old groups (P=0.007),while there was no significant difference (P＞0.013) between the 18-39 and 40-59 years old groups.The detection rate of esophagitis was significantly higher in ≥60 years old group than in 18-39 and 40-59 years old groups (P=0.004,P=0.008),while no significant statistically difference (P＞0.013) was found between the later two groups.Conclusions Gastroscopy can be used as a basic examination means for GERD;short segment hiatal hernia can be regarded as an early form of hiatal hernia,and is of important reference value for the diagnosis and treatment of GERD;more serious hiatal hernia and esophagitis could be found in elderly GERD patients.

Hypoxia induces the migration of endothelial progenitor cells / 中国组织工程研究

BACKGROUND: Local endothelial progenitor cells (EPCs) have been reported to promote migration and homing of EPCs by releasing stromal cell-derived factor-1 (SDF-1) under hypoxia environment. OBJECTIVE: To investigate the effect of different hypoxia periods on the expression of SDF-1 protein in EPCs and the migration of EPCs, thus providing new ideas for the treatment of ischemic diseases. METHODS: The bone marrow of the long bone was removed from Sprague-Dawley rats used for isolate EPCs. After culture and identification, EPCs were divided into four groups: control (normoxia), 6-, 12- and 24-hour hypoxia groups. The expression level of SDF-1 in the supernatant of EPCs in each group was detected by ELISA and immunofluorescence. The mRNA and protein levels of SDF-1 were detected by RT-PCR and western blot assay. The effect of hypoxia on the migration of EPCs was tested by Transwell assay. RESULTS AND CONCLUSION: The obtained cells were identified as EPCs. ELISA and immunofluorescence results showed that compared with the control group, the expression level of SDF-1 began to increase at 6 hours of hypoxia, peaked at 12 hours of hypoxia, and then decreased at 24 hours of hypoxia. RT-PCR and western blot assay results found that the mRNA and protein expression levels of SDF-1 were the highest in the 12-hour hypoxia group, followed by 6- and 24-hour hypoxia groups, and the lowest in the control group (P < 0.01). The number of EPCs penetrating the membrane in the 12-hour hypoxia group was significantly more than that in the 6- and 24-hour hypoxia groups, and the number in the 24-hour hypoxia group was significantly more than that in the control group (P < 0.05). In summary, hypoxia can promote the secretion of SDF-1 and induce the migration of EPCs.

Optimization of isolation and culture of LinSca-1cardiac stem cells from newborn mice / 生理学报

Cardiac stem cells (CSCs) transplantation has been recognized to be effective on the treatment of myocardial infarction (MI), but some techniques still need to be developed in the isolation and culture of CSCs, which is the key problem restricting the clinical application of CSCs. This study was focused on the isolation of Lin(lineage-negative) Sca-1(stem cell antigen-1-positive) CSCs from newborn C57BL/6J mice (0-3 d) by mixed enzymatic-explant isolation in combination with immunomagnetic separation. The digesting time, digesting frequency, incubation temperature, stirring speed, centrifugation time and rotational speed were strictly controlled in the experiment. In order to increase the survival rate of CSCs, the medium changing time and manner were optimized in primary CSCs culture. The percentages of Sca-1cells in primary and passage cells were detected by flow cytometry and immunofluorescence staining. The results showed that: (1) the proportion of LinSca-1cells within the collected cells could be as high as (85.03 ± 5.60)% after isolation and purification; (2) In vitro culture of LinSca-1CSCs grew into spheres on the 5day, and over the whole bottom of the dish on the 7day. The growth curve showed that the cells were in logarithmic growth phase on the 3day; (3) Immunofluorescence staining data showed that the expression of Sca-1, the CSCs membrane-specific marker, was decreased after subculture, and flow cytometry data showed that the percentages of Sca-1cells were (71.82 ± 2.63)%, (58.38 ± 3.70)% and (46.19 ± 4.72)% in passage 1 (P1), P3, and P5 CSCs, respectively. The above results suggest that high purity of LinSca-1CSCs can be obtained by enzymolysis combined with immunomagnetic separation method. Moreover, the CSCs culture system is stable. In our experiment, the Sca-1CSCs isolation and culture method has been successfully established, and it is simple, stable, effective and reliable. The method can provide a stable methodological basis for the treatment of MI by LinSca-1CSCs transplantation.

Excimer laser atherectomy combined with drug-eluting balloon angioplasty for the treatment of chronic ischemia of lower limbs: preliminary results in three patients / 介入放射学杂志

Objective To evaluated the safety and feasibility of excimer laser atherectomy (ELA) combined with drug-eluting balloon angioplasty in treating chronic ischemia of lower limbs.Methods ELA combined with paclitaxel-eluting balloon angioplasty was adopted to treat chronic ischemia of lower limbs caused by arteriosclerosis occlusive disease of lower extremity in three patients.All three patients had arteriosclerosis occlusive disease of superficial femoral artery;in two of them the disease was primary occlusive lesion and in another patient the disease was in-stent re-occlusion lesion after sten implantation.Results After the treatment,the blood flow in the diseased arteries was unobstructed,the blood supply of the lower limbs was obviously improved.No procedure-related complications occurred.Two weeks after the treatment,no recurrence of ischemic symptoms was observed,the blood flow in superficial femoral artery kept unobstructed.The patients recovered smoothly.Conclusion For the treatment of chronic ischemia of lower limbs,which are caused by the primary arteriosclerosis occlusive disease of lower extremity or by the in-stent re-occlusion lesion after sten implantation,ELA combined with paclitaxel-eluting balloon angioplasty is clinically safe and feasible,although its long-term effect needs to be clarified with more studies.

Iatrogenic gastrointestinal perforation following therapeutic endoscopic procedures: management and outcome

The aim of this study was to analyze the location, the cause and treatment of iatrogenic gastrointestinal perforations following therapeutic endoscopic procedures. Perforation occurred in 12 patients out of 3,389, giving cases occurred intraoperatively or postoperatively. Among them, 6 cases were closed by titanium clipping and 1 case by purse string suture. In another case after cap-assisted endoscopic mucosal resection [EMRC], attempted titanium clipping failed, emergency surgery had to be performed. One each case, after Argon plasma coagulation [APC] and case after endoscopic piecemeal mucosal resection [EPMR], recovered well spontaneously. In two cases, titanium clips fell off endoscopic mucosal resection [EMR] resulting in delayed perforation, required surgery. Key factors for preventing and managing the perforation of endoscopic treatment, include the choice of endoscopic approach, processing method of perforation, detail processing in endoscopic therapy, proficient degree of operators and psychological quality

The development of cell-penetrating peptides in drug delivery system / 药学学报

Cell membrane serves as the natural barrier. Cell-penetrating peptides (CPPs) have been a powerful vehicle for the intracellular delivery of a large variety of cargoes cross the cell membrane. The efficiency of intracellular delivery of drugs, proteins, peptides and nucleic acid, as well as various nanoparticu-late pharmaceutical carriers (e.g., liposomes, polymeric micelles and inorganic nanoparticles) has been demon-strated both in vitro and in vivo. This review focuses on the CPPs-based strategy for intracellular delivery of small molecule drugs, proteins, peptides, nucleic acid and CPP-modified nanocarriers.

Efficacy analysis of percutaneous microwave ablation in treatment of hepatic metastases from gastric adenocarcinoma after gastrectomy / 中国医师进修杂志

Objective To evaluate the efficacy of of percutaneous microwave ablation(MWA) in treatment of hepatic metastases from gastric adenocarcinoma after gastrectomy. Methods Twenty-four patients who underwent percutaneous MWA after gastrectomy for a hepatic metastasis from a gastric cancer from October 2009 to October 2014. Median age was (63 ± 11) years. Three-two times MWA was done in 27 metastatic tumors. Patients′ outcomes were assessed by enhancement CT or MRI. Results The rate of total ablation was 92.6%(25/27). The deadline of follow up was 2016-04-01. One patient was living and 23 patients died with tumor progression. The median overall survival was 24.1(95%CI:9.8-34.3) months. The survival rate of 1, 2, 3, 4 and 5 years was 78.7%, 40.7%, 38.5%, 19.4%and 8.2%. The median progression-free survival was 13.4 (95%CI:2.0-30.4) months, and the survival rate of local progression-free of 6 months, 1, 2 and 3 years was 64.3%, 50.1%, 40.2%and 26.9%. The main complication was moderate and severe pain in 10 cases, and 17 cases had post ablation syndrome. Conclusions For patients with metastatic tumors≤3 cm, MWA is a safe and feasible treatment option for hepatic metastases from gastric adenocarcinoma.

Efifcacy of early combination treatment with intratympanic glucocorticoid injection for sudden hearing loss / 中国耳鼻咽喉头颈外科

[ABSTRACT]OBJECTIVETo investigate the therapeutic effect of early combination treatment with intratympanic glucocorticoid injection for sudden sensorineural hearing loss(SSNHL).METHODSTotal of 178 patients with diagnosis of SSNHL, including 44 with hearing loss at middle-low frequencies,50 at high frequencies,44 at all frequencies and 40 at total deafness, were randomly divided into combination treatment group (CT group) and systemic oral prednisone group (OP group).CT group (82 patients) received intratympanic administration of methylprednisolone and oral prednisone in tapering doses. Pure-tone threshold audiometry (PTA) was performed at week 8 after beginning of therapy. RESULTSIn middle-low frequencies, the final PTA and PTA improvement were 26.14±24.82 dB and 42.23±1.61 dB in CT group respectively, and were 37.91±13.98 dB and 30.00±13.30 dB in OP group respectively (both P<0.05). In high frequencies, all frequencies and total deafness SSNHL group, the differences of the final PTA and PTA improvement were not statistically significant in both groups. The PTA improvement in CT group for total deafness (26.52±14.03) dB was more than that of OP group (22.06±11.17)dB (t=2.361,P<0.05). In middle-low frequencies, the recovery rate was 72.73%(16 cases) in CT group, and 40.91% (9 cases) in OP group, the difference was significant (χ2=4.539,P<0.05), but not in apparent effective rate, effective rate and total effective rate. In high frequencies, all frequencies and total deafness, there were no significant differences in therapeutic effect. The recovery rate of total CT group (40.24%) was significantly increased compared with that of OP group (26.04%)(χ2=4.061,P<0.05), the differences of apparent effective rate, effective rate and total effective rate were not statistically significant in both groups.CONCLUSIONFor low-middle frequencies SSNHL, the early combination treatment with intratympanic glucocorticoid injection leads to higher hearing recovery and therapeutic effect compared with traditional oral prednisone. Systemic application should be applied for high frequencies, all frequencies and total deafness of SSNHL.

Endovascular therapy for complex subclavian artery occlusive diseases / 介入放射学杂志

Objective To discuss the key points of endovascular therapy for complex subclavian artery occlusive diseases. Methods During the period from January 2012 to December 2013, a total of 92 patients with complex subclavian artery occlusive disease were admitted to Xuanwu Hospital of Capital Medical University, Beijing, China. The clinical data were retrospectively analyzed. The features of the lesions, the success rate of endovascular therapy, the use of combined approaches, the relief of symptoms after treatment, etc. were evaluated. Results The complex subclavian artery occlusive diseases could be divided into three types. Type Ⅰ: long segment of the left subclavian artery was occluded; type Ⅱ: ostial stenosis or occlusion of the right subclavian artery; and type Ⅲ: subclavian artery stenosis or occlusion was associated with the ostial disorder of the vertebral artery, or the opening of vertebral artery was affected by the subclavian artery stenosis or occlusion. The technical success rate was 82.6%. Combination use of femoral artery and brachial artery approach was employed in 27.2% of patients, which had improved the technical success rate. After the treatment the symptom improvement rate was 81.6%. Conclusion Upper limb artery approach can improve the re-canalization rate of left subclavian artery with long segment occlusion, and can ensure the accurate positioning of stent at the site of right subclavian artery opening. During the procedure of endovascular intervention for subclavian artery occlusion disease, attention should be paid to the protection of the vertebral artery.

Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles / 华中科技大学学报（医学）（英德文版）

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.