Parkinson′s disease(PD)is a common disease caused by multiple factors and characterized by pathological degen?eration in the dopaminergic neural system. Based on its pathogenic factors,PD can be divided into several subtypes,so it is essential to develop therapeutic agents based on the main pathogenic factor of each subtype of PD. Recently it is confirmed that the mutation of leucine-rich repeat kinase 2(LRRK2)gene leads to increased activity of the LRRK2 notably,and then causes neurodegeneration. Thus developing LRRK2 inhibitors to modulate the kinase activity will be a novel therapy for the PD subtype which is caused by LRRK2 gene mutation. LRRK2,either a kinase or a GTPase,has two drug binding sites. Therefore,two types of LRRK2 inhibitors are being studied,one is the kinase inhibitor and the other is GTPase inhibitor. This paper summarizes the recent progress in the dis?covery and development of LRRK2 inhibitors.

This paper introduces the comparative approach including its implication,implementing ways and values in efferent nervous pharmacological teaching from characteristics of efferent nervous pharmacology.It can be concluded that comparative approach is the suitable teaching method in the teaching of efferent nervous pharmacology.

Objective To compare and evaluate the efficacy of diagnosis and excision for appropriately selected breast multi-focal lesions and solitary lesion by ultrasound-guided vacuum-assisted biopsy (UGVAB). Methods Among 392 appropriately selected patients, 187 patients with multi-focal lesions and 205 patients with solitary lesion were treated by the 8-gauge UGVAB from May 2007 to June 2009. All lesions were removed as completely as possible. The patients with benign pathology underwent physical and ultrasound examinations at one week and 6 months after procedure. Results During the procedure, only three patients had vasovagal syncope and twenty others complained of other intraoperative discomfort. An accurate pathological diagnosis was obtained in all lesions. There was no apparent false-negative result among the 696 lesions with benign pathology at a follow-up of 6 months after procedure. The rates of malignant or premalignant pathology, postoperative complications and residual lesions in patients with multi-focal lesions were higher than those in patients with solitary lesion. If each lesion was considered as a subject of study, there was no significant difference between the two groups. Conclusion UGVAB is an effective method for diagnosis and excision of appropriately selected breast multi-focal lesions and can be used routinely.

AIM: To study the effects of protein kinase C (PKC) inhibitor, chelerythrine chloride (CH), on nociceptive response, nitric oxide synthase (NOS) expression and nitric oxide (NO) content in spinal cord of rats with inflammatory pain. METHODS: Inflammatory pain was induced by formalin injection into right hind paw. NADPH-d histochemistry was used to investigate the changes of NOS expression. Nitrate/nitrite (NO_2-/NO_3-) was assayed to represent NO content. RESULTS: Compared with the control group, the number of NADPH-d positive cells increased significantly in the superficial layer (LaminaeⅠ-Ⅱ) of the spinal cord dorsal horn and the grey matter surrounding the central canal (Laminae Ⅹ) in rats with inflammatory pain, the reactive degree of NADPH-d positive soma and fibers and NO content of the lumbar enlargement of spinal cord also increased significantly. Intrathecal injection of CH inhibited the spontaneous pain response in the second phase induced by formalin injection, and prevented the increases in the number and reactive degree of NADPH-d positive cells, as well as NO content of the lumbar enlargement of spinal cord. CONCLUSION: It is suggested that the activation of PKC promotes NOS expression and NO production in the nociceptive neurons of spinal cord during formalin-induced inflammatory pain.

Objective To explore the effects of comprehensive restraint reduction program on preventing un-planned extubation among ICU patients with tracheal intubation. Methods Totally 266 cases of ICU patients with tracheal intubation in our hospital were selected as the research objects using the convenient sampling method.They were divided into two groups by time: the experimental group of 130 cases implementing a comprehensive reduction constraint program and the control group of 136 cases using conventional physical restraint in nursing process.The constraint rate, constraint length, UEX incidence, skin and satisfaction of the two groups were compared. Results In the experimental group, the rate of physical restraint and UEX decreased, the average restraint length of each patient was shortened, skin integrity at the site of restraint improved, and the satisfaction of patients increased. Compared with the control group, the differences were statistically significant(P<0.01 or P<0.05). Conclusion The com-prehensive restraint reduction program can reduce the rate of physical restraint and the incidence of unplanned ex-tubation among ICU patients with tracheal intubation.

AIM: To explore the effect of allicin on hippocampal neuronal apoptosis induced by global cerebral ischemia - reperfusion and its mechanisms. METHODS: Wistar rats were subjected to 15 min global cerebral ischemia followed by 72 h reperfusion. Flow cytometry (FCM) was used to evaluate the rate of hippocampal neuronal apoptosis and colorimetric method was used for the measurement of nitric oxide (NO) , malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity in hippocampal tissue. RESULTS: Neuronal apoptotic rate, nitric oxide and malondialdehyde contents in hippocampal tissues of rats in I - R group were significantly higher than those in sham group. However, superoxide dismutase activity in hippocampal tissues of rats in I - R group was obviously lower than that in sham group. Allicin pretreatment inhibited the above changes in a dose-dependent manner. CONCLUSION: Allicin hihibits hippocampal neuronal apoptosis induced by global ischemia-reperfusion insult through anti - oxidation. The anti - oxidation action of allicin may be one of the mechanisms of inhibitory effects on hippocampal neuronal apoptosis.

Objective To study the expression of copper transport protein 1 in the inner ear of rat and the changes of CTR1 expression after those round window niche copper sulfate and cisplatin infusion .Methods 24 male wistar rats were randomly divided into 4 groups :Group I as the normal control group (nontreatment group);Group II as the round window niche cisplatin infusion group(0 .5 mg/ml);Group III as the round window niche cisplatin infusion group (1 mg/ml);group IV as the round window niche copper sulfate infusion (0 .02 mg/kg) .The CTR1 protein was detected by the immunohistochemical (IHC) otaining and Western-blot ,and the CTR1mRNA expres‐sion levels were detected by RT -PCR .Results The expression of CTR1 protein was observed in the cytoplasm and cell membrane of Corti organ cells ,spiral ganglion cells and stria vascularis in all groups .The average optical densi‐ties of CTR1 protein was a downward trend .The expression of CTR1 protein was observed in four different groups . The optical density analysis of CTR1 showed that the optical densities were 0 .532 ± 0 .031 ,0 .394 ± 0 .024 ,0 .234 ± 0 .030 and 0 .191 ± 0 .015 ,respectively .There was a downward trend ,and there were statistically differences among the groups (P<0 .05) .The CTR1 mRNA was observed in all groups .The optical density analysis of CTR1 mRNAshowed that the optical densities were 0 .508 ± 0 .035 ,0 .391 ± 0 .022 ,0 .240 ± 0 .02 and 0 .186 ± 0 .021 ,respective‐ly .It had a downward trend and were statistically differences among the groups (P<0 .05) .Conclusion The CTR1 protein was abundantly expressed in Corti organ ,spiral ganglion cells and stria vascularis of the cochlea .The round window cisplatin and copper sulfate infusion can change the expression of CTR1 proteins in inner ear .

Testicular allotransplantation is one of the effective options for the treatment of male infertility and hypogonadism. Since the first experimental testis transplantation, nearly 3 centuries have passed and great strides have been made in this field. Nevertheless there remain some problems that call for the attention of the medical world. Based on varieties of related literature, this paper gives a general review of the history, the status quo and the prospects of testicular allotransplantation.
Animals ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Testis ; transplantation ; Transplantation, Homologous ; history ; trends

Objective: To study the effect of postoperative application of tranexamic acid on recovery and prognosis of unilateral total hip arthroplasty. Methods: One hundred and twenty patients who received unilateral total hip arthroplasty in 541st General Hospital of Dongzhen Town from August 2016 to August 2018 were divided into observation group and control group by random number table method, with 60 cases in each group. The control group received intravenous injection of tranexamic acid 10 min before skin incision after anesthesia; on the basis of the control group, the observation group was given tranexamic acid intravenously again 3 h after operation, and the control group was no longer given repeated injection of tranexamic acid. The hemorrhage, hemoglobin (Hb), hematocrit(HCT), hip joint Harris score and complications were compared between the two groups. Results: There was no significant difference in intraoperative blood loss and transfusion between the two groups (P>0.05); the drainage volume, total blood loss, dominant blood loss and recessive blood loss in the observation group were lower than those in the control group [(227.43 ± 20.14) ml vs. (280.91 ± 23.56) ml, (601.01 ± 42.84) ml vs. (667.04 ± 49.21) ml, (281.93 ± 18.50) ml vs. (322.06 ± 21.23) ml, (330.94 ± 21.73) ml vs. (370.03 ± 25.90) ml] (P<0.05). After operation 3 d, the levels of Hb and HCT in observation group were higher than those in control group [(117.07 ± 9.60) g/L vs. (102.19 ± 8.31) g/L, (35.05 ± 2.91)% vs. (32.01 ± 2.77)%] (P<0.05). After operation 2 weeks and 1 month after operation, the hip joint Harris score in observation group was higher than that in control group [(52.03 ± 4.02) scores vs. (48.37 ± 5.05) scores, (67.86 ± 5.29) scores vs. (61.23±5.10) scores] (P<0.05). There was no significant difference in the occurrence of intermuscular venous thrombosis, local hematoma and incision exudation between the two groups(P>0.05). Conclusions On the basis of preoperative application of tranexamic acid, combined postoperative application of tranexamic acid can significantly reduce the blood loss after unilateral total hip arthroplasty, and help the early recovery of joint function, without increasing complications and with high safety.

BACKGROUNDAllergic asthma is associated with airway inflammation and hyperresponsiveness caused by dysregulated production of cytokines secreted by allergen-specific helper T-type 2 (Th2) cells. The linker for activation of T cells (LAT) is a membrane-associated adaptor protein, which has been shown to take part in regulating T cell receptor (TCR) signaling and T cell homeostasis. In this study, we established an asthmatic mouse model to examine the changes in LAT levels during allergic airway disease and the effects of LAT transgenic expression on airway inflammation.

METHODST cells from mouse lung tissues were isolated from allergen challenged (ovalbumin (OVA)) and control mice, and the purity of these isolated T cells was examined by fluorescence-activated cell sorter (FACS). Semi-quantitative RT-PCR and Western blotting were used to detect the expression of the LAT gene and LAT protein, respectively. After an intranasally administered mixture of pCMV-HA-LAT plasmid and Lipofectamine 2000, 24 hours before and 72 hours after allergen challenge, the BALF cell count and the differential cytologies were studied. In addition, IL-4 and IFN-γ levels in the BALF were determined by ELISA, and pathological changes in lung tissues were observed.

RESULTSLAT protein and mRNA expression were decreased in lung T cells in a mouse model of allergen-induced airway disease. After intranasal administration of pCMV-HA-LAT, histopathological examination of the lungs showed that intervention with LAT overexpression prevented mice from developing airway inflammation, and the number of total cells, eosinophils, neutrophils, and lymphocytes in the BALF was reduced significantly compared with the OVA sensitized and challenged group. In addition, the Th2 cytokine IL-4 decreased, while the Th1 cytokine IFN-γ increased compared to the OVA sensitized and challenged group or the OVA sensitized group plus pCMV-HA treatment.

CONCLUSIONThis study demonstrates that LAT might effectively diminish Th2 cytokine responses, lung histopathological changes and lung inflammation to allergen challenge in a model of experimentally induced asthma.

Animals ; Asthma ; immunology ; metabolism ; Blotting, Western ; Bronchoalveolar Lavage Fluid ; immunology ; Cells, Cultured ; Cytokines ; metabolism ; Female ; Inflammation ; immunology ; Mice ; Mice, Inbred BALB C ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes ; immunology ; metabolism