This article reviews the resultsof the basic research about epidermal growth factor and its receptor,and the development of the novel drug, EGF eyedrop, that containing chemically synthesised EGF gene,the construction of EGF expression vector, the transformation of the host cells , the purification of the recombinant protein EGF, the preparation of three batches of the EGF product and identification, the preclinical and clinical trials. Relevant studies show that recombinant EGF consisting of 51 amino acids can be secreted into the medium under the control of the α factor leading sequence in the yeast cells.The EGF can accelerate the growth of corneal-limbal epithelial cells and the healing of an alkali burned corneal. The EGF can be used in curing oral cavity ulcer and skin burned wound. And it has the preventive effects on experimental duodenal ulcer of rat. The antiserum was made for test of the con- centration of blood EGF and urine EGF by RIA. Data from studies demonstrate the inhibition effect of EGF on the growth of tumor cells, such as A431 and BT325 cells in the presence of high EGF concentration (＞10 ng/ml). The expression of EGFR and DNA ploidy in renal carcinoma has clinical significance. Crystallization and preliminary x-ray diffraction studies of the EGF has been made. The MW of the EGF product is 6000, and the pI is about 4. 6 and it has correct N-terminal amino acids sequences , immunogenicity and biological activity. There is no vestige of the DNA of the yeast cells. Animal experiments reveal that there is no cumulation of the EGF in the body, and EGF can promote corneal epithelial healing. There is no toxicological effect during cornea wound healing of rabbit. A randomized, double-blind, placebo-controlled, multi-center clinical trial was conducted in four hospitals to assess safety,ocular tolerance and efficacy of an ophthalmic solution of EGF for 200 cases of cornea transplantation and 247 cases of nebulae. Unequivocal results were obtained as the eyedrop really accelerate the wounded cornea healing. So, the EGF eyedrop as a novel drug of class I is approved by the National Drug Administration, and this is the first gene engineering drug that come from yeast expression system in China.

BACKGROUND: Brain-derived neurotrophic factor(BDNF) is a potent dopaminergic neurotrophin. The major pathological change in Parkinson disease(PD) is the degeneration and death of dopaminergic neurons in the substantia nigra pars compacta. There is a possibility that the onset of PD is associated with BDNF genetic polymorphisms.OBJECTIVE: To investigate the relationship between BDNF genetic polymorphisms and sporadic Parkinson disease(SPD) in Chinese population with the expectation of offering some genetic data for the primary rehabilitation and prevention of the disease.DESIGN: Explorative study based on DNA samples of SPD patients as study group and DNA samples of healthy population as control group.SETTING: Neurological Department of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Human Genome Center of Huazhong University of Science and Technology.PARTICIPANTS: Subjects included DNA samples of 85 SPD patients(study group, Han population, living in Huazhong area for a long term) offered by Department of Neurology of Wuhan Union Hospital and DNA samples of health persons(control group, Han population, living in Huazhong area for a long term) offered by Human Genome Center of Huazhong University of Science and Technology.METHODS: The genotype of healthy controls and SPD patients was analyzed with the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP).MAIN OUTCOME MEASURES: Genotypes and alleles of the two polymorphisms: G196A and C270T of the two groups.RESULTS: G/A genotype was dominant in both SPD patients and control group with frequencies of 50.6% and 52.0% respectively. The C/C genotype occurred with the frequency of 100% in both groups. There were no significant differences in genotype and allele frequencies of G196A and C270T between SPD and control group( P ＞ 0. 05).CONCLUSION: No association existed between BDNF genetic polymorphisms and the onset of SPD in Chinese Han population of Huazhong area.

Objective To establish an early cognitive disorder model in rats and investigate the early cognitive functioning after ischemic hypoxic brain injury during the neonatal period. Methods Forty-six newborn Sprague-Dawley rats were randomized into a 21-d-old group and a 31-d-old group. These 2 groups were then subdivided into model and sham-operated subgroups (M21, n=12; SH21, n=11; M31, n=12; SH31, n=11). A model of neonatal early cognitive disorder was established in the rats of the M21 and M31 groups using a modification of Rice's method. Rats in the SH21 and SH31 groups received skin incisions and common carotid artery separation without ligation or hypoxia. Each group was tested with a Morris water maze. The rats were sacrificed after testing, and brain tissue was examined under the electron microscope. Nissl staining allowed Nissl body quantification and neurocyte acin the M21 group was significantly longer than in the SH21 group. The 31-d-old subgroups had shorter average escaping latencies than the corresponding 21-d-old subgroups. (b) Spatial memory: The average platform times, Ⅰ region times and Ⅰ region distances showed no significant differences among groups. ②Brain pathology (a) Gross appearance: Obvious ischemic hemisphere atrophy was observed in the M group, and no abnormality was observed in the SH group. (b) Electron microscopic observation: In the SH group cell ultrastructures in the ischemic hippocampus were normal. Karyopyknosis and dilated endoplasmic reticulums were found in the M group. More mitochondria were found in the presynaptic membranes of the ischemic hippocampus in the M group than that in the SH group. (c) Nissl body quantification and neurocyte activity analysis: Significantly less activity in the ischemic cortex was found in the M21 group compared to the SH21 group. More activity was observed in the 31-d-old subgroups than in the corresponding 21-d-old subgroups. Conclusions ①The neonatal rats with ischemic hypoxic brain injury had prolonged average escaping latency and depressed neuronal activity. ②The 31-d-old rats had better spatial localization learning ability than the 21-d-old rats.

In this study, the human umbilical vein endothelial cell model was used to study the regulating effect of lipophilic components in Salvia miltiorrhiza on angiogenesis, and explore its possible mechanism. The cell model was established to determine the effect of lipophilic components in S. miltiorrhiza on the proliferative activity and migration capacity of endothelial cells. Then the realtime fluorescence quantification PCR technology was applied to detect the changes in the gene expressions of angiogenesis-related cytokines VEGF-A, VEGF-C and MMP-9. The results showed that 5 mg x L(-1) lipophilic components in S. miltiorrhiza could inhibit the proliferation and migration of endothelial cells, and reduce the expression of VEGF-A and MMP-9 genes. It indicated that lipophilic components in S. miltiorrhiza may inhibit the proliferation and migration of endothelial cells by inhibiting the expression of VEGF-A and MMP-9 genes, so as to show the inhibitory effect on angiogenesis.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

The data mining technique is adopted to analyze characteristics and rules of acupoint and meridian selection of acupuncture-moxibustion for treatment of vertigo at different time periods in the ancient. The data is collected from literature regarding acupuncture-moxibustion from the pre-Qin period to the end of Qing Dynasty, so as to establish a clinical literature database of ancient acupuncture-moxibustion for treatment of vertigo. Data mining method is applied to analyze the commonly used meridians, acupoints and special acupoints in different dynasties, also possible rules are explored. Totally 82 pieces of prescription of acupuncture-moxibustion for treatment of vertigo are included. In the history the leading selection of acupoitns are Fengchi (GB 20), Hegu (LI 4), Shangxing (GV 23) and Jiexi (ST 41) while that of meridians are mainly three yang meridians of foot and the Governor Vessel, especially the acupoints on the Bladder Meridian of foot yangming had the highest utilization rate, accounting for 23.04%. The acupoint selection is characterized by special acupoint, accounting for 80.6%, among which the crossing points are the most common choice. Distal-proximal acupoints combination is the most frequent method. The results indicate that the ancient acupuncture-moxibustion for treatment of vertigo focused on acupoints in the yang meridians, and the specific acupoints play an essential role in prescription; also the principle of syndrome differentiation and selecting acupoints along the meridians could be seen.
Acupuncture Points ; Acupuncture Therapy ; history ; Data Mining ; History, 18th Century ; History, 19th Century ; History, 20th Century ; Humans ; Medicine in Literature ; Moxibustion ; history ; Vertigo ; history ; therapy

Studies have shown that a variety of diseases such as cardiovascular disease, renal disease and cancer are closely related to trimethylamine oxide (TMAO). Clinically, abnormal elevation of TMAO has been used as an evaluation index of atherosclerosis (AS) prior to imaging. In this study, we investigated the effects of lipid metabolism disorders as well as pharmacological interventions on urinary TMAO using a hyperlipidemic golden gopher model. The study used 48 Syrian golden hamster modeled with a high-fat diet for 2 weeks, and then ezetimibe, simvastatin, ezetimibe and simvastatin groups were administered for 4 consecutive weeks, as well as the clinical trial drug, IMM-H007, for pharmacological intervention. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: SCXK (Beijing) 2021-0011). Urine from rats was analyzed for 2D band selective heteronuclear single quantum coherence (2D bs-HSQC) at week 2 and 4 after drug administration. The results indicated that, in comparison to the control group, the high-fat diet significantly elevated urinary TMAO levels in the model group of hamsters after both 2 and 4 weeks of treatment (P < 0.05). Urinary TMAO levels were significantly reduced (P < 0.05) in the model group after 2 or 4 weeks of intervention with ezetimibe, simvastatin, combination therapy, and IMM-H007, showing a marked decrease even after 2 weeks of treatment. The detection of TMAO could precede the measurement of serum biochemical indicators, facilitating earlier efficacy assessment. This study evaluated the modulatory effects of clinical drugs and clinical trial drugs on TMAO, which provides useful information for clinical drug use and drug research. It also provides a means of TMAO detection based on 2D NMR technology, which is helpful for the clinical application of TMAO detection index.

OBJECTIVETo evaluate computed tomography (CT) and magnetic resonance imaging (MRI) findings in patients with autoimmune pancreatitis (AIP).

METHODSThe imaging findings of pancreas and extra-pancreas in 24 patients with AIP were retrospectively reviewed. Among them, CT scan was performed in 18 patients, MRI in 11, and bGth CT and MRI in 10.

RESULTSThe pancreas showed diffuse enlargement (25%, 6/24), focal enlargement (37. 5%, 9/24), combined enlargement (25%, 6/24) ,and no enlargement (12. 5%, 9/24). Unenhanced CT showed hypoattenuation in AIP area (n = 2) . After intravenous injection of contrast medium, 17 patients showed abnormal contrast enhancement in the affected pancreatic parenchyma, including hypoattenuation during the arterial phase (50%, 9/18) and hyper attenuation during the delayed phase (94. 4%, 17/18). Precontrast MRI showed abnormal signal intense (n =9), including hypointense on T1-weight images (T1 WI) (n = 7), hyperintense (n = 7) and hypointense (n = 2) on T2-weight images (TIWI). Enhanced MRI demonstrated abnormal contrast enhancement within lesions (n = 11), including hypoattenuation during the arterial phase (81. 8%, 9/11) and good enhancement during the delayed phase (100%, 11111). A capsule-like rim was seen around pancreas (37. 5%, 9/24), among which CT detected in 6 out of 18 patients and MRI found in 7 out of 11 patients.The main pancreatic duct lumen within lesions has no visualization (100%, 24/24) and upstream dilation of the main pancreatic duct (n = 8) , ranging from 2. 2 to 4. 5 mm(mean 3. 1 0. 47 mm) in diameter. Narrowing of the common bile duct was shown in 14 patients. Miscellaneous findings were: infiltration of extrapancreatic vein (n = 9) and artery (n = 1); mild fluid collection around pancreas (n = 2); pseudocysts (n = 3). Fourteen patients also presented one or more of the following extrapancreatic imaging findings: narrowing of the intra-hepatic bile duct or hilar duct (n = 5); thickening of gallbladder wall (n = 5); fibrosis in mesenteric (n = 2), in retroperitoneal (n = 2) and in ligamentum teres hepatis (n = 1); renal involvement (n = 3); peri-pancreatic or para-aortic lymphadenopathy (n = 10); and ulcerative colitis (n = 3).

CONCLUSIONAIP display some characteristic CT and MRI imaging features: sausage-like change of the pancreas; capsule-like rims around lesions; delayed contrast enhancement in the affected pancreatic parenchyma; segment or diffuse pancreatic duct stenosis but mild upstream dilation and extrapancreatic organs involvement. CT and MRI findings combining with serological tests and pancreas biopsy can assist physicians to make accurate and timely diagnosis.

Adult ; Aged ; Autoimmune Diseases ; diagnosis ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pancreas ; diagnostic imaging ; pathology ; Pancreatitis ; diagnosis ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVETo investigate the effects of Shexiang Baoxin Pill (SBP) on function of endothelial progenitor cells (EPCs) and its nitric oxide (NO) secretion.

METHODSTotal mononuclear cells were isolated from human peripheral blood by ficoll density gradient centrifugation and inoculated on the human fibro-ligandin encrusting plate. After 7 days of in vitro culture, adherent cells were collected and incubated with SBP for 24 h. The proliferation, migration, adhesive activity, vasculogenesis capacity and NO secretion of EPCs were assayed using MTT, Transwell chamber, adhesion determination, in vitro vasculogenesis kit and nitrate reductase method, respectively.

RESULTSEPCs incubated with SBP showed the capacities higher than those of control in proliferation, migration, adhesion, in vitro vasculogenesis, and with a higher NO concentration in the culture supernatant.

CONCLUSIONSBP can improve the function of EPCs, which might be a novel mechanism of its effects in improving vascular endothelial function and promoting angiogenesis.

Cell Differentiation ; physiology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; cytology ; metabolism ; physiology ; Humans ; Leukocytes, Mononuclear ; cytology ; Nitric Oxide ; biosynthesis ; Stem Cells ; cytology ; metabolism ; physiology

OBJECTIVETo observe the impact of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture on mRNA expression of lung inflammatory cytokines and pulmonary pathological injury of mice infected by influenza virus, in order to discuss the mechanism of tonifying Qi traditional Chinese medicines against pulmonary immune inflammatory injury of infected mice.

METHODIn different time phases after mice were infected with influenza virus FM1, the RT-PCR method was adopted to observe the impact of tonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture on five inflammatory cytokines TNF-α, IL-1, IL-6, IL-10 and IFN-γ, and the changes in pulmonary pathological injury of mice with viral pneumonia after intervention with tonifying qi traditional Chinese medicines.

RESULT(1) Tonifying Qi traditional Chinese medicines significantly reduced the mRNA expression of TNF-α at 1-5 d and IL-1 mRNA expression at 7 d, may increase IL-1 mRNA expression in mouse lung at 3 d, significantly reduced IL-6 mRNA expression in mouse lung and increased IL-10 mRNA expression at 3-7 d, and significantly increased IFN-γ mRNA expression at 1 d. (2) Tonifying Qi traditional Chinese medicines could significantly inhibited and repaired pulmonary immune inflammatory injury of mice infected by FM1, which was most remarkable at 3-7 d after the infection with influenza virus FM1.

CONCLUSIONTonifying Qi traditional Chinese medicines contained in Yiqi Qingwen Jiedu mixture could resist pulmonary immune inflammatory injury and repair inflammatory injury by regulating the mRNA expression of imbalance inflammatory cytokines of organisms infected with influenza virus.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Influenza A virus ; drug effects ; immunology ; Influenza, Human ; drug therapy ; genetics ; immunology ; Interferon-gamma ; genetics ; immunology ; Interleukin-1 ; genetics ; immunology ; Interleukin-10 ; genetics ; immunology ; Interleukin-6 ; genetics ; immunology ; Lung ; immunology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; genetics ; immunology