Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Phytotherapy ; Severe Acute Respiratory Syndrome ; drug therapy ; prevention & control

Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×10⁴, and the effective concentration of the positive drug was 1-100 µmol·L^-1. In addition, pretreated with 10 µmol·L^-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L^-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.

This study investigates the protective role of IMM-H004, a novel coumarin derivative, on hepatic ischemia-reperfusion injury (HIRI) in mice. All animal experiments in this paper have been approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The experimental animals were divided into three groups, including sham group, model group, and IMM-H004 treatment group. Serum biochemical indicators were detected and H&E staining was used to assess liver damage. Real-time quantitative PCR (qPCR) was performed to analysis the mRNA content of inflammatory factors. Immunohistochemistry and immunofluorescence were used to observe neutrophil infiltration. Western blot was used to examine the protein levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and interleukin-1β (IL-1β). The results showed that IMM-H004 could significantly reduce the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH). H&E results showed IMM-H004 could alleviate liver damage caused by HIRI. The mRNA expression of tumor necrosis factor-α (TNF-α), IL-1β, and interleukin-6 (IL-6) were decreased by IMM-H004 administration. Meanwhile, IMM-H004 could markedly inhibit neutrophil infiltration. Furthermore, IMM-H004 could significantly down-regulate the protein expression of NLRP3, ASC, caspase-1, and IL-1β, inhibiting the activation of NLRP3 inflammasome pathway. Our results confirmed that IMM-H004 could protect mice from HIRI and provide a theoretical foundation for IMM-H004 application for treating HIRI.

Phytoestrogens, which can bind with estrogen receptor and produce estrogen-like effects, are a kind of nonsteroidal compound in plant. Phytoestrogens chemically include isoflavones, coumarins, lignans and other compounds. Phytoestrogens are selective estrogen receptor modulator, and have therapeutical effects on breast cancer, prostate cancer, cardiovascular disease, menopausal symptoms, osteoporosis and other disease, however, do not produce stimulatory hyperplasia effects on uterus, mammary glands and other tissues and organs with positive estrogen receptor. Long-term exposure or excessive use of phytoestrogens maybe affects male reproductive system and hematopoietic function of fetus. Some questions need to be further studied, such as evaluation criteria on biological activity, adverse effects, and action mechanism of phytoestrogen. This review covers plant sources, chemical structure, pharmacological activity and safety of phytoestrogens. It will provide a useful reference for intensive research and rational utilization the phytoestrogens.
Animals ; Humans ; Phytoestrogens ; chemistry ; pharmacology ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry

Background Human paired box gene 6 (PAX6)encodes a transcriptional regulator.It is essential for eye and brain morphogenesis.Mutation of PAX6 gene isresponsible for many congenital ocular malformations,such as aniridia.Aniridia is a autosomal dominant inheritance mode.Objective In this study,PAX6 gene mutation was analyzed in three Chinese families with aniridia through polymerase chain reaction (PCR) and sequencing.Methods The blood specimens were collected from 5 suffers and normal individuals of 3 aniridia families to extract DNA.The sequences of extron 4-13 were designed based on PAX6 gene.The primer was amplified by PCR and sequenced and compared with the known PAX6 gene sequence.This study complied with Declaration of Helsinki and approved by ethic committee of Sichuan University.Written informed consent was obtained from each individual before any medial examination.ResultsThere were 5 suffers in the 3 families.A heterozygous mutation (c.718 C＞T) in PAX6 gene was identified in 2 patients of family A.This mutation caused an amino acid substitution of arginine to termination codon at position 240 ( p.Arg240X) of PAX6 protein.No similar change in the normal families.No any the alteration of PAX6 gene was detected in family B whatever suffers and normal individuals.In family C,a deletion mutation of c.331 delG ( p.Val111 SerfsX13 ) in PAX6 gene was found.The deletion of one base caused frame shift mutation of PAX6 protein,and no such mutation was seen in other families.Conclusions Mutation of PAX6 gene appeares to be causative mutations of the disease in family A and C.

Objective To study the expression level of peptidylarginine deiminase 4 (PADI4) and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in the synovium of rat model of collagen-induced arthritis, and to explore their possible therapeutic role in rheumatoid arthritis.
Methods Thirty-two female Wistar rats weighing 100±20 g were randomly assigned into 3-week collagen-induced arthritis (CIA) model group (n=8), 4-week CIA model group (n=8), 6-week CIA model group (n=8), and the control group (n=8). The body weight changes of each group were recorded. The expression levels of PADI4 and PTPN22 were detected and compared by the methods of immunohistochemical staining and Western blot.
Results Arthritis of rat began to form 14 days after sensitization and the joint swelling reached peak at 28 days. The weights of the rats slowly grew both in CIA model groups and the control group. Immunohistochemical staining results showed that the positive expression of PADI4 and PTPN22 was mainly located in cartilage peripheral mononuclear cells, the cytoplasm of infiltrated cells, and bone marrow cavity. There were significant differences in the optical density of PADI4 and PTPN22 among CIA model groups and the control group (PADI4, 0.2898±0.012, 0.2982±0.022, 0.2974±0.031, 0.2530±0.013 in 3-week CIA model, 4-week CIA model, 6-week CIA model and control groups;PTPN22, 0.2723±0.004, 0.2781±0.010, 0.2767±0.008, 0.2422±0.019;all P<0.05). The expression bands of PADI4 were observed in Western blot 3 weeks after initial immunization, the thickest in the 4th week, and decreased in the 6th week. The expression bands of PTPN2 were observed at all the time points, with no obvious time-dependent trend.
Conclusions PADI4 and PTPN22 are obviously correlated with CIA in rat model. PADI4 is expressed at early stage of the disease, while the expression of PTPN22 sustains throughout the course.

OBJECTIVETo investigate the incidence of the temporary and permanent sensory disturbance of the inferorbital nerve (ION) after Le Fort I osteotomy.

METHODSThirty patients with 60 inferorbital nerves were examined preoperatively, 1 week, 1 month, 3 months and 6-months after the operation of the Le Fort I osteotomy by using sharp-blunt testing, 2-point discrimination, electric pain response test (ZGK-1 electrometer).

RESULTSThe incidence of the temporary nerve impairment was 75% (45 of 60) and the obvious recovery was found after 1 to 3 months after the operation. No permanent sensory disturbance was found in the patients.

CONCLUSIONSThe inferorbital nerve injury after Le Fort I osteotomy is usually temporary and the sensory recovery was in 1 to 3 months after the operation.

Adolescent ; Adult ; Cranial Nerve Injuries ; etiology ; rehabilitation ; Female ; Follow-Up Studies ; Humans ; Male ; Osteotomy, Le Fort ; adverse effects ; methods ; Postoperative Complications ; etiology ; rehabilitation ; Time Factors

The purpose of this study is to explore the clinical significance of RBC blood group serological test in nonmyeloablative allogeneic peripheral blood stem cell transplantation (NAPBSCT) of ABO group incompatibility in 4 patients with acute leukemia. ABO and MN blood group of donors and recipients were determined by hemagglutination test and Rh blood group by Diana Gel phenotype Rh card. The changes of blood group in recipients were observed and implant of donor cells was monitored by short tandem repeat-PCR method. The results showed that in 2 cases of 4 recipients the marrow cells appeared mixed chimera of donor and recipient cells, and blood group changed to donor type in 1 of the 2 cases on 100 days after transplantation. In another 2 cases, the marrow cells appeared mixed chimera without blood group chimera on 154 days after transplantation, and rejection of the transplant occurred in 1 of the 2 cases. The determination of hemagglutinin titer showed that the implant rate of donor cells was lower in the recipients with higher hemagglutinin titer and blood group chimera did not appear, conversely, the implant rate was higher in the recipients with lower titer and blood group chimera appeared early. It is concluded that examination of RBC blood group in NAPB SCT can indirectly reflect effectiveness of transplantation, contribute to decide the intensity of conditioning protocol and immunosuppressive therapy after transplantation, estimate prognosis and guide blood transfusion during transplantation.
Adult ; Blood Group Antigens ; Blood Transfusion ; Female ; Humans ; Leukemia, Myeloid, Acute ; blood ; therapy ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; therapy ; Transplantation, Homologous

Alzheimer's disease (AD) has become one of the major diseases that plague human health and seriously affect the quality of life of patients. Up to present there is no specific treatment drug for Alzheimer' s disease, which still needs research and development. Ginseng is an important traditional Chinese medicine in the prescription for treating of Alzheimer's disease, which contains saponins, polysaccharides, volatile components, proteins, vitamins, amino acids and other compounds. Saponins are the main active components, which have a good effect on improving learning and memory ability and preventing AD. In this paper, the effect and the mechanism of ginsenosides for treating AD are reviewed in order to provide ideas for developing ginsenosides into drugs with better clinical compliance and more effective treatment of AD.

OBJECTIVETo observe the curative effects of bone marrow stem cell (BMSC) and peripheral blood stem cell (PBSC) transplantations on the avascular necrosis of femoral head (ANFH).

METHODSTotally 122 ANFH patients (211 coxae) treated by BMSC or PBSC transplantations were enrolled from July 2004 to December 2006. All of them were classed to different stages according to the ARCO. Control group were desired as themselves before and after treatment. The puncture of femoral artery was conducted with digital subtraction angiography (DSA), and the tubes were inserted into medial femoral circumflex artery, lateral femoral circumflex artery and obturator artery with the cell suspensions were gradually poured into the arteries.

RESULTSThe joint pain, joint functions and walking distance of 122 patients were detected for the follow-up. Compared with before treatment, the calibers thickened; vessels increased and blood velocity quickened of femoral head blood-supply artery were observed in 15 patients after 6 months checked by DSA. The reduced areas of femoral head necrosis in 8 patients indicated the new bone formation between 12 and 24 months.

CONCLUSIONSAutologous BMSC and PBSC transplantation results in the new bone formation and improvement of ischemia in areas of femoral head necrosis at 6 months. The change of angiography was observed about 12 to 24 months after cell transplantation. The stem cell transplantation is convenient, safe and effective in the treatment of the ANFH with no adverse reaction, and can be considered as a new therapy of ANFH.

Bone Marrow Transplantation ; Femur Head ; blood supply ; pathology ; surgery ; Femur Head Necrosis ; surgery ; Follow-Up Studies ; Humans ; Ischemia ; surgery ; Peripheral Blood Stem Cell Transplantation ; Stem Cell Transplantation ; methods ; Transplantation, Autologous ; Treatment Outcome