Progress in controlled ocular anti-VEGF drug release delivery system / 中华实验眼科杂志

Neovascularization is the hallmark of many fundus diseases, including diabetic retinopathy, retinal vein occlusion and neovascular age-related macular degeneration.More and more evidence suggests that vascular endothelial growth factor (VEGF) plays a critical role in neovascularization.Anti-VEGF drugs are the first-line treatment for neovascular fundus diseases and have achieved significant results.However, there are drawbacks such as short drug half-lives and the need for long-term administration to maintain effective concentrations, which increases the economic burden and medical risk for patients and reduces compliance.Therefore, finding a new method for intraocular drug delivery is of great clinical importance.Based on the principle that diabetes patients use insulin pumps to gradually release drugs, the ocular anti-VEGF drug delivery system can continuously release anti-VEGF drugs over a period of time, significantly reducing the injection frequency and improving patient compliance.At present, the research on ocular anti-VEGF drug delivery systems is still immature, and various systems are in different stages of clinical trials.According to different design principles, they can be divided into three categories with their characteristics, micropump (extraocular storage delivery systems), biodegradable implants, and non-biodegradable implants.This article summarized and analyzed the controlled ocular anti-VEGF drug release delivery systems currently in clinical trials.

A novel O-methyltransferase with substrate promiscuity from Ardisia japonica / 药学学报

italic>O-methyltransferases (OMTs) are one of the key tailoring enzymes in the biosynthesis of many natural products, O-methylation can not only reduce the reactivity of natural products, but also alter their solubility, stability and biological activities. Based on the transcriptome data of Ardisia japonica, a full-length cDNA sequence of candidate OMT (termed as AjOMT1) was cloned by reverse transcription-polymerase chain reaction (RT-PCR) and expressed in Escherichia coli (E. coli) for the first time. In vitro enzyme catalytic activity assay showed that the recombinant AjOMT1 could effectively catalyze quercetin to form O-methylated products. Most importantly, AjOMT1 showed unprecedented substrate promiscuity towards structurally various compounds including flavonoids, stilbenes, coumarins, alkaloids and phenylpropanoids, especially preferring to the compounds with adjacent phenolic hydroxyl groups, and showed regio-selectivity. These results suggested that AjOMT1 could be used as the tool enzyme to conduct O-methylation of different types of compounds to produce diverse active methylated products, and provide a new method for drug discovery, even universal part for synthetic biology of natural products.

A rare case of purulent pericarditis secondary to subdiaphragmatic abscess / 世界急诊医学杂志（英文）

@#Subdiaphragmatic abscess is the accumulation of pus in the space between the diaphragm and the transverse colon and its mesentery.[1] Subdiaphragmatic abscess is clinically characterized by fever and local pain. Its clinical manifestations are often vague and diverse, and its symptoms and signs together constitute thoracoabdominal syndrome, leading to delayed diagnosis and a high incidence rate and mortality.[2]Subdiaphragmatic abscess is often secondary to acute peritonitis or remote infection with hematogenous dissemination. The bacteriological characteristics of these abscesses include aerobic and facultative bacteria, such as Escherichia coli, group D Enterococcus and Staphylococcus aureus, as well as less common anaerobic organisms, such as Bacteroides.[3] In 1938, Ochsner and DeBakey recognized chest complications of subdiaphragmatic abscesses, including empyema, bronchial fistula, and pericarditis, in their classic review of subdiaphragmatic abscesses. Because of the structural characteristics of the diaphragm, there are fewer complications of diaphragm perforation.[4] Especially now, with the use of antibiotics, these complications have become more rare. Here, we report a case of purulent pericarditis caused by Klebsiella pneumonia, secondary to subdiaphragmatic abscess extending through the diaphragm.

Single-molecule imaging reveals stoichiometry of vascular endothelial growth factor receptor 2 in retinal vascular endothelial cells / 中华眼底病杂志

Objective:To observe the stoichiometry of vascular endothelial growth factor receptor 2 (VEGFR2) on the retinal vascular endothelial cell membrane by single-molecule fluorescence imaging.Methods:Rhesus monkey retinal vascular endothelial cells (RF/6A) were divided into blank control group (normal culture) and plasmid transfection group [transfected with VEGFR2-green fluorescent protein (GFP) recombinant plasmid]. The expression of GFP in the plasmid transfected group was observed by confocal microscope, and the expression of VEGFR2 in the cells was detected by real-time fluorescent quantitative polymerase chain reaction (qPCR) and Western blot. The fluorescence intensity distribution and bleaching steps of single VEGFR2-GFP molecule on the cell membrane were recorded by single-molecule imaging. The distribution of fluorescence intensity and the number of fluorescence bleaching steps of GFP were recorded.Results:GFP green fluorescence was observed in the transfected cells 12 hours after transfection. qPCR results showed that the expression of VEGFR2 and GFP mRNA in the plasmid transfected group was significantly higher than that in the blank control group ( t=11.240, 12.330; P<0.001, 0.001). Western blot results showed that the expression of VEGFR2 protein in the plasmid transfected group was significantly higher than that in the blank control group ( t=8.346, P<0.01). The results of single-molecule imaging showed that the fluorescence intensity distribution of VEGFR2-GFP on the surface of RF/6A cell membrane without ligand stimulation was bimodal, in which monomer and dimer were 86.0% and 14.0% respectively. By counting the steps of GFP fluorescence bleaching, the proportions of receptor monomer, dimer, trimer, and tetramer were 81.4%, 12.9%, 5.5%, and 0.3% respectively. Conclusion:In the absence of ligands, VEGFR2 coexists in the form of monomers and dimers on the surface of RF/6A cell membrane, and monomers are dominant.

Research progress of anti-vascular endothelial growth factor receptor 2 drugs in the treatment of retinal neovascularization disease / 中华眼底病杂志

Neovascularization is a characteristic manifestation of a variety of retinal diseases. Vascular endothelial growth factor (VEGF) mainly regulates the proliferation and migration of endothelial cells. VEGF receptor 2 (VEGFR2) is the main receptor to mediate this effect. The activation of downstream signals requires the binding of VEGF and VEGFR2, followed by receptor dimerization and autophosphorylation. Blocking this process and inhibiting neovascularization is very attractive treatment ideas. Monoclonal antibodies and fusion protein drugs currently used in ophthalmology can bind free VEGF. In addition, there are also macromolecular antibodies binding VEGFR2 and small molecule tyrosine kinase inhibitors, which is expected to further expand into the field of ophthalmology. Although anti-VEGFR2 therapy is a revolutionary method to inhibit neovascularization, there are no sufficient clinical evidences at present. In-depth understanding of the application status and progress of anti-VEGFR2 in the treatment of retinal neovascular diseases has important clinical significance.

Identification and verification of effective components of Huanghuai for dysfunctional uterine bleeding based on network pharmacology and molecular docking / 中草药·英文版

Objective: The Huanghuai (HH), which is made from the dried roots of Scutellaria baicalensis (Huangqin in Chinese) and the dried flowers and buds of Sophora japonica (Huaihua in Chinese), is a traditional Chinese formula used to treat dysfunctional uterine bleeding (DUB) (Benglou in Chinese) and proven to treat hemostasis effectively in our previous study. Network pharmacology and molecule docking were performed to study the underlying mechanism of Huanghuai (HH), and pharmacodynamic experiments were conducted to verify its curative effect. Methods: TCMSP, UniProt, GeneCards, STRING, DAVID databases, and Cytoscape 3.7.2 were utilized for the construction of a compound-target-pathway network. Docking the potential effective components with potential targets. The HPLC analysis of the potential effective components was performed. In vivo, the hot plate test model was used to study the analgesic activity, the egg white was used to study the swollen reaction in the sole in mice, and the hemostasis effect was studied by the capillary method, tail-breaking method and abortion uterus test. Results: The results showed that six compounds (acacetin, beta-sitosterol, wogonin, baicalein, kaempferol and quercetin) and four potential targets (PTGS2, AKT1, TP53 and TNF) in the compound-target-pathway network were the potential material basis for HH to treat DUB. It can be seen that the binding energy of the acacetin, wogonin, baicalein, beta-sitosterol, kaempferol and quercetin in HH docked with the receptor proteins PTGS2, AKT1, TP53, and TNF were far less than −5.0 kJ/mol, which means the molecules have low conformational energy, stable structure and high binding activity. And the result of HPLC analysis showed that acacetin, wogonin, baicalein, kaempferol and quercetin were the potential effective components of the hemostasis mechanism of HH, beta-sitosterol was removed due to low content. In vivo testing of the potential effective components, it revealed that the group of potential effective components identified by HPLC could increase the pain threshold, inhibit the swelling hind paws of mice induced by egg white, reduce the bleeding time and clotting time, reduce uterine bleeding, decrease the uterine weight, increase the content of Ca and ET-1, and reduce the content of NO in uterine homogenate tissue, and decrease of E

Establishment of HPLC fingerprints of Qiwei Tangmaishu tablet and simultaneous determination of six constituents / 国际药学研究杂志

Objective: To establish HPLC fingerprints of Qiwei Tangmaishu tablet and simultaneously determine the contents of the six constituents, acteoside, martynoside, calycosin 7-O-β- D-glucopyranoside, schisandrin, formononetin and deoxyschizan- drin. Methods: The analysis of 50% methanol extract of this drug was performed on a 30℃ thermostatic Waters Symmetry C18 column, with the mobile phase comprising of acetonitrile(A)-0.2% formic acid solution(B)flowing at 1.0 ml/min in a gradient elution manner. The detection wavelength was set at 330 nm for acteoside and martynoside, 254 nm for calycosin 7-O-β-D-glucopyranoside, schisandrin, formononetin and deoxyschizandrin. Results: There were thirteen common peaks in the fingerprints of ten batches of samples with the similarities more than 0.9. Acteoside, martynoside, calycosin 7-O-β-D-glucopyranoside, schisandrin, formononetin and deoxyschizandrin showed good linear relationship within the ranges of 1.47-36.75, 0.66-16.50, 0.89-22.25, 2.58-64.50, 1.91-47.75 and 0.77-19.25 μg/ml(r≥0.9993), and their average recoveries were 97.57%, 99.22%, 96.69%, 100.01%, 98.79% and 96.77%, with the RSD of 0.79%, 1.54%, 0.61%, 0.64%, 0.83% and 0.36%, respectively. Conclusion: The established method is easily operable and repeatable, which could be used for quality control of Qiwei Tangmaishu tablet.

UGT88B2: A promiscuous O-glycosyltransferase from Carthamus tinctorius / 中草药·英文版

Objective: In order to obtain new glycosyltransferases with highly efficient catalysis, the glycosyltransferases from Carthamus tinctorius which contains diverse types of glycosides were mined. Methods: A new glycosyltransferase gene (UGT88B2) with full length was obtained by PCR and further transformed into Escherichia coli for heterologous expression. The catalytic activity of recombinant UGT88B2 was determined by HPLC-MSn. The structures of representative catalytic products were elucidated by MS and NMR. Results: UGT88B2 exhibited catalytic promiscuity and various patterns in glycosylation of flavonoids with high efficiency. Conclusion: A new glycosyltransferase named UGT88B2 was successfully mined and can be employed as enzymatic tools in glycosylation of flavonoids.

Application of "priority approach of uncinate process" in laparoscopic pancreaticoduodenectomy:A report of 200 cases / 中国实用外科杂志

OBJECTIVE: To explore the value of "priority approach of uncinate process" in laparoscopic pancreaticoduodenectomy. METHODS: The data of 200 patients who underwent laparoscopic pancreaticoduodenectomy in the No.2 Department of Hepatobiliarypancreatic Surgery, the First Hospital of Jilin University from April 2015 to October 2018 were analyzed retrospectively. RESULTS: All the 200 patients successfully completed laparoscopic pancreaticoduodenectomy, including 1 case of laparoscopic pancreaticoduodenectomy combined with right hemicolectomy,2 cases of laparoscopic pancreaticoduodenectomy combined with pancreaticocotailectomy,and 2 cases of laparoscopic pancreaticoduodenectomy combined with portal vein reconstruction(end-to-end anastomosis). The mean operation time was(281±49)min,including the specimen removal time(91±15)min,and the intraoperative blood loss was 50-850 mL(122±53)mL. The mean postoperative hospital stay was(16±9)days. Eight-teen cases(9.0%)had grade B pancreatic fistula and 3 cases(1.5%)had grade C pancreatic fistula. Postoperative anastomotic bleeding in 2 cases(1.0%). Intraperitoneal hemorrhage was found in 14 cases(7.0%), and delayed gastric emptying in 9 cases(4.5%).Biliary fistula was found in 11 cases(5.5%). There were 2 deaths(1.0%). Postoperative pathological diagnosis showed that ductal adenocarcinoma of the head of pancreas was in 33 cases(16.5%),the pancreas intraductal papillary mucinous tumor in 15 cases(7.5%),head of the pancreatic neuroendocrine tumors in 6 cases(3.0%),pancreatic ductal epithelial hyperplasia in 1 case(0.5%),solid pancreatic head fake papilloma in 9 cases(4.5%),pancreatic head capsule adenomas in 5 cases(2.5%),chronic pancreatitis in 1 case(0.5%),duodenal adenocarcinoma in 4 cases(2.0%), duodenal stromal tumor in 2 cases(1.0%), duodenal benign space-occupying lesions in 11 cases(5.5%),periampullary carcinoma of non pancreatic head origin in 105 cases(52.5%)and benign periampullary tumors in 9 cases(4.5%). CONCLUSION: "Priority approach of uncinate process" is safe,rapid and effective in laparoscopic pancreaticoduodenectomy,which is worthy of further promotion and application in clinic.

Visualization study of outdoor activities affecting the development of children’s myopia / 中国学校卫生

Objective@#To explore the international development trends and research hotspots of outdoor activities affecting the progression of children’s myopia, and to provide a reference for researching on effective ways to prevent children’s myopia.@*Methods@#Totally 291 relevant documents included in the "Web of Science" core set database were used as research objects, and CiteSpace software was used for visual analysis.@*Results@#At present, the publications in this field were mainly in the United States(81), China(80), Australia(76), and Singapore(33); the top three research institutions were "Natl Univ Singapore"(29), "Australian Natl Univ"(27), "Capital Med Univ"(25); the main authors were "Saw SM", "Morgan IG", "Mitchell P". The field has been developed on the basis of "Ophthalmology", "Public, Environmental and Occupational Health", and has been integrated into 32 disciplines. The research content included "exploration of high risk factors for the progression of children’s myopia" and "outdoor activities", "intervention in children’s progression of myopia" and "longitudinal tracking of children’s vision development". Randomized clinical trials that longitudinally track the correlation between changes in eyeballs and the progression of myopia and the effects of outdoor activities on the biological characteristics of children’s eyeballs have become a hot topic in this field.@*Conclusion@#Research on the effects of outdoor activities on the progression of myopia in children has increased dramatically. The study of increasing outdoor activities to interfere with the progression of myopia in children and the vertical tracking of key factors affecting the biological characteristics of children’s eyeballs have become the current international trends.

Development and prospect of dynamic dummy research / 医用生物力学

The dynamic dummy plays an important role in the research of protecting human beings from impact environment. To collect data from dummy in dangerous impact tests is the fundamental method used in developing protection equipment and systems in aerospace, automobile and other industries. The performances of a dummy depend on its simulation degree, as well as the quality and quantity of sampled signals. The dummy technology abroad is now indispensable in developing the protection of aviation ejection and rescue system, and also beneficial to automobile and other industries. China had no Chinese characterized dummy applied until the year of 2003 when the dynamic dummy was created in Institute of Aviation Medicine, and the dummy has equivalent high performance as that made by the United States and has been availably exerted in aviation. For evaluating the impact injuries on Chinese human beings, it is necessary to further develop Chinese characterized dummy series, and to establish the all-around criteria by strengthening application of digital virtual dummy in impact environment study.

Pilot load analysis under Herbst maneuver based on flight simulation / 医用生物力学

Objective To obtain the multi-axis load histories on physiological coordinate of the pilot when performing Herbst maneuver by flight simulation, and make analysis on the obtained typical data. Methods The 3D geometrical model of the aircraft was established in CAD software based on design parameters of the fourth-generation aircraft, 6 key motion parameters of mass center were obtained by flight simulation, and 3D human body model was developed according to anthropometric measurement data of Chinese male pilot; based on the location of cabin and seat in the aircraft, the assembly model with both the aircraft and human body was established and the multi-axis load histories at different locations of human body under Herbst maneuver were obtained through kinematics analysis of the human-aircraft system. An analytic case of Herbst maneuver at altitude of 3 km and flight velocity of 90 m/s was carried out. Results The load histories at chest, foot and head of human body were basically coincided, but Gy histories between the chest and hand were different; the Gy peak value of hand was about 1.6 g; under the multi-axis loads, the +Gx peak value was about 3.0 g, being the maximum. Conclusions The load histories of aircraft mass center cannot be used as those of human body because it may have some deviation, and the Gy histories for hand cannot be replaced by load histories of other locations on human body when they are used for analysis on effects of multi axis load on operating behaviors of the aircraft.

Dynamic responses of head-neck complex in pilots during arrested deck landing / 医用生物力学

Objective To analyze the dynamic response and strain of the major muscles in head-neck complex of pilot with or without wearing the helmet during carrier aircraft arrested deck landing. Methods Ten-rigid body dynamic model of human head-neck complex was created including head, seven cervical vertebrae and two thoracic vertebrae; mechanical properties of the ligaments, intervertebral discs and other surrounding soft tissues were described by lumped parameter method; mechanical properties of the 15 pairs of muscles in this human head-neck complex were represented by non-linear stress-strain relationship. The model was validated by using experimental data of dynamic responses from the human head-neck complex in a set of different types of automobile crashes. Results The overload curve and strain of this 15 pairs of muscles in head-neck complex of the pilot during arrested deck landing were obtained. The results showed that the extension of splenius cervicis was the largest. The strain of splenius cervicis could reach 50% when the pilot wore the helmet, and it could reach as high as 56% if the helmet’s weight was 2.7 kg. Conclusions Wearing helmet would extend the stretch of neck muscles, and the simulation result could be used for further evaluation on head/neck injury of the pilot.

Study on neck injuries in military pilots / 医用生物力学

Objective To investigate the present situation of neck injuries in military pilots, analyze possible factors that induce neck injuries and how such injuries could influence flight training, and provide suggestions for relevant physiological researches and engineering solutions. Method Questionnaires were carried out among 1 924 military pilots, including pilots of primary trainer, attacker, fighter, bomber, transporter and helicopter. The questionnaire consist of 2 parts: (1) pilots’ basic information, such as unit, age, type of aircraft, flying hours, height, weight, etc. (2) relevant issues on neck injuries, including symptoms and their influences on flight, reasons that cause the injuries, etc. Statistical analyses were conducted according to the questionnaire results. Results The investigation showed that 71.3% of the pilots had uncomfortable neck symptoms and 60.4% of them had befallen such symptoms during flight. 33.7% of the pilots had suffered neck pain and 19.2% of them reported that such pains took place during flight. Factors such as acceleration, weight of helmet and long duration of flight would be the main reasons resulting in the discomfort of neck. Bomber pilots showed the highest proportion either on the neck discomfort or on the neck pain. Conclusions Neck injuries have become the frequently occurring illness in Chinese military pilots and have affected their daily flight. The study also foresees an increased tendency on pilots’ neck injuries due to the growing requirements of flight load and training strength on fighter and attacker pilots. Therefore, great importance should be attached on neck injuries of military pilots and further studies should be conducted on physiological investigations and engineering solutions.

Application of emulational trunk dummy in evaluating the opening shock of life saving parachute / 医用生物力学

Objective To carry out quantitative investigation on application of emulational trunk dummy (ETD) in evaluating the opening shock of life saving parachute and provide a more reliable test method for further development. Method ETD equipped with parachute was tested in the impact experiment, where a 63.4 kg impact block was dropped from the height of 0.20 m，0.40 m，0.60 m，0.80 m respectively to simulate different opening shocks. The opening shocks were deducted by measured forces on harness and acceleration loads at the center of dummy's thorax. For comparison, 5 rigid trunk dummies (RTD) were tested under the equivalent impacts. As the contrast test, 24 male healthy subjects were also exposed under such impacts with standing and sitting posture respectively. Results Under the same impact, the peak impact value on harness exhibited maximum on RTD, minimum on subjects with sitting posture, and medium on ETD. There were significant differences between each experimental group (P<0.01). With different impact loads, the peak impact value on ETD was 2 795，3 873，4 816 and 5 736 N respectively, which was correspondingly close to that of subjects with standing posture(2 541，3 042，3 720 and 4250 N). Conclusions The result of opening shock gathered from ETD is closer to that from RTD due to ETD’s viscoelasticity, which shall certainly influence the measured opening shock. Therefore, ETD is suggested to be used in the development of live saving parachute.

Biomechanics in aviation / 医用生物力学

Pilots are usually under various different mechanical loads during flights, which can affect their musculoskeletal and cardiovascular system and even bring them injuries. Biomechanics mainly studies the mechanics and mechanobiology in medicine and biology. Aviation biomechanics studies the physiological response to different complicated mechanical loads during flights and the countermeasures. The research fields of aviation biomechanics include: mechanical loads on human body injury and related countermeasures, durative loads, vibration and noise on the physiological effects of human body and related comtermeasures, etc.

The study of EEG Higher Order Spectral Analysis technology / 中国医疗器械杂志

The basic theory of Higher Order Spectral Analysis and the most generally used Bispectrum are introduced in the paper. By certain experiments of EEG signal acquisition and bispectrum analysis, it is showed that the Higher Order Spectrum has an advantage over power spectrum, which is based on Second Order Statistics, in processing non-linear signal and restraining Gauss noise signal.

Anti-tumor activity of Actinidia chinensis planch / 中国药理学通报

Aim To evaluate the anti-tumor activity of the extract from the root of Actinidia chinensis planch in vitro and in vivo. Methods Active components from the root of Actinidia chinensis planch were isolated by traditional phytochemical techniques. The in vitro anti-tumor activity was determined by sulforhodamine B assay and the in vivo anti-tumor activity was evaluated using experimental mouse tumor models and human tumor xenografts in nude mice. Results Powdered air-dried roots of Actinidia chinensis planch were percolated with methanol at room temperature thrice. The filtrate was concentrated to dryness in vacuo and then was further extracted with ethyl acetate, n-butanol , and chloroform. The fraction extracted by chloroform displayed the most potent activity against several tumor cell lines including hepatocellular carcinoma Bel-7402 cells, non-small cell lung cancer A549 cells, lymphoma Ramos cells, and breast cancer MCF-7 cells. Further more, the anti-tumor efficacy of the chloroform fraction was confirmed in Bel-7402 xenografts in nude mice with the percentage inhibition of 38.0 %. Conclusion The extract of the root of Actinidia chinensis planch has anti-tumor activity, and the active components are mainly in the fraction extracted by chloroform.