Tongxie Yaofang regulates tumor-associated macrophage polarization in colorectal cancer under chronic stress / 中国中药杂志

This study aims to investigate the intervention effect and mechanism of Tongxie Yaofang in regulating tumor-associated macrophage polarization on colorectal cancer under chronic stress. BALB/C mice were randomized into blank, control, model, mifepristone, and low-, medium-, and high-dose Tongxie Yaofang groups. The other groups except the blank and model groups were subjected to chronic restraint stress and subcutaneous implantation of colon cancer cells for the modeling of colon cancer under stress. Du-ring this period, the body mass and tumor size of each group of mice were recorded. The degree of depression in mice was assessed by behavioral changes. Enzyme-linked immunosorbent assay was employed to determine the levels of cortisol(CORT), 5-hydroxytryptamine(5-HT), norepinephrine(NE), M1-associated inflammatory cytokines [interleukin(IL)-1β, IL-12, and tumor necrosis factor(TNF)-α], and M2-associated inflammatory cytokines(IL-4 and IL-10) in the serum. The tumor growth of mice in each group was regularly monitored by in vivo imaging. The histopathological changes of tumors in each group of mice were observed by hematoxylin-eosin staining. The proportions of CD86 and CD206 in the tumor tissue were detected by flow cytometry and immunofluorescence staining. Western blot was employed to determine the protein levels of Janus kinase(JAK)1, JAK2, JAK3, signal transducer and activator of transcription(STAT)3, and STAT6 in the tumor tissue. The results showed that chronic stress increased the immobility time of mice, elevated the serum levels of CORT, IL-4, and IL-10, lowered the levels of 5-HT, NE, IL-1β, IL-12, and TNF-α, and promoted the growth of subcutaneous tumors. The tumor cells in the tumor tissue grew actively, with obvious atypia and up-regulated protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and down-regulated protein level of CD86. The treatment with Tongxie Yaofang shortened the immobility time of mice, lowered the serum levels of CORT, IL-4, and IL-10, elevated the serum levels of 5-HT, NE, IL-1β, IL-12, and TNF-α, and inhibited the growth of subcutaneous tumors in mice. Moreover, the treatment caused different degrees of necrosis in the tumor tissues, down-regulated the protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and up-regulated the protein level of CD86. In summary, Tongxie Yaofang can promote the transformation of M2 macrophages to M1 macrophages and change the tumor microenvironment under chronic stress to inhibit the development of colorectal cancer, which may be related to the JAK/STAT signaling pathway.

Decursin affects proliferation, apoptosis, and migration of colorectal cancer cells through PI3K/Akt signaling pathway / 中国中药杂志

We investigated the effects of decursin on the proliferation, apoptosis, and migration of colorectal cancer HT29 and HCT116 cells through the phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway. Decursin(10, 30, 60, and 90 μmol·L~(-1)) was used to treat HT29 and HCT116 cells. The survival, colony formation ability, proliferation, apoptosis, wound hea-ling area, and migration of the HT29 and HCT116 cells exposed to decursin were examined by cell counting kit-8(CCK8), cloning formation experiments, Ki67 immunofluorescence staining, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blot was employed to determine the expression levels of epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2-associated X protein(Bax), tumor suppressor protein p53, PI3K, and Akt. Compared with the control group, decursin significantly inhibited the proliferation and colony number and promoted the apoptosis of HT29 and HCT116 cells, and it significantly down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. Decursin inhibited the wound healing and migration of the cells, significantly down-regulated the expression of N-cadherin and vimentin, and up-regulated the expression of E-cadherin. In addition, it significantly down-regulated the expression of PI3K and Akt and up-regulated that of p53. In summary, decursin may regulate epithelial-mesenchymal transition(EMT) via the PI3K/Akt signaling pathway, thereby affecting the proliferation, apoptosis, and migration of colorectal cancer cells.

Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

The Value of CD44 / 中国实验血液学杂志

OBJECTIVE@#To investigate the value of CD44@*METHODS@#Flow cytometry was used to detected the proportion of CD44@*RESULTS@#The percentage of CD44@*CONCLUSION@#HCD44

Relationship between Leukocytes Derived Microparticles and Minimal Residual Disease and Prognosis of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To detect the relationship between leukocytes derived microparticle (CD45@*METHODS@#The expression of CD45@*RESULTS@#The percentages of CD45@*CONCLUSION@#High level of CD45

Comparative study on curative effect of minimally invasive locking plate for the treatment of intra-articular calcaneal fractures via sinus tarsi approach / 中国骨伤

OBJECTIVE@#To compare clinical efficacy of minimally invasive locking plate and anatomic locking plate in treating intra-articular calcaneal fractures via sinus tarsi approach.@*METHODS@#A retrospective analysis was conducted of 48 patients with intra-articular calcaneal fractures treated with surgery via sinus tarsi approach from July 2016 to June 2017. According to differernt methods of internal fixation, the patients were divided into minimally invasive locking plate group and anatomic locking plate group. In minimally invasive locking plate group, there were 14 males and 10 females, aged from 27 to 46 years old with an average age of (38.70±5.58) years old, 18 patients were typeⅡand 6 patients were type Ⅲ according to Sanders classification. In anatomic locking plate group, there were 17 males and 7 females, aged from 26 to 46 years old with an average age of (37.10±6.44) years old, 16 patients were typeⅡ and 8 patients were type Ⅲ according to Sanders classification. Operative time, visual analogue scale (VAS), postoperative complications between two groups were compared, and Böhler angle, Gissane angal, calcaneal width and height were recorded and compared between two groups at 1 week after operation and final follow up. The functional effect was assessed according to Maryland foot function score at final follow up.@*RESULTS@#All patients were followed up for (14.10±1.94) months (ranged 12 to 18 months). All patients were obtained bone union from 8 to 16 weeks with an average of (10.60±2.25) weeks. Operation time, VAS score and complication rate in minimally invasive locking plate group were (69.50±7.51) min, (2.80±1.07) and 2 cases respectively, and (77.50±7.15) min, (3.80±1.09) and 8 cases in anatomic locking plate group respectively, there were statistical difference between two groups (@*CONCLUSION@#Compare with anatomic locking plate, minimally invasive locking plate via sinus tarsi approach for Sanders typeⅡ and Ⅲ intra-articular calcaneal fractures could obtain similar reliable fixation and functional recovery with more simple operation, shorter operative time, lighter postoperative pain and less complications.

Translational Advances in Cancer Prevention Agent Development (TACPAD) Virtual Workshop on Immunomodulatory Agents: Report

The National Cancer Institute (NCI) Division of Cancer Prevention (DCP) convened the “Translational Advances in Cancer Prevention Agent Development (TACPAD) Workshop on Immunomodulatory Agents” as a virtual 2-day workshop on September 13 to 14, 2021. The main goals of this workshop were to foster the exchange of ideas and potentially new collaborative interactions among leading cancer immunoprevention researchers from basic and clinical research and highlight new and emerging trends in immunoprevention. The workshop included an overview of the mechanistic classes of immunomodulatory agents and three sessions covering the gamut from preclinical to clinical studies. The workshop convened individuals working in immunology and cancer prevention to discuss trends in discovery and development of immunomodulatory agents individually and in combination with other chemopreventive agents or vaccines.

Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

Value of three-dimensional visualization technology in preoperative evaluation of liver autotransplantation for end-stage hepatic alveolar echinococcosis / 中国血吸虫病防治杂志

Objective To evaluate the value of the three-dimensional visualization technology for the preoperative assessment of liver autotransplantation for end-stage hepatic alveolar echinococcosis. Methods A total of 8 patients with end-stage hepatic alveolar echinococcosis undergoing liver autotransplantation in Qinghai Provincial People’s Hospital from May 2013 to July 2017 were collected. All cases received preoperative abdominal CT scanning and dynamic three-phase enhanced CT scanning, and the original CT data were transferred to the human 3D visualization virtual surgical planning system. The volumes of Echinococcus multilocularis and pre-resected liver were measured using the 3D visualization reconstruction, and the relationship between the lesion and the neighboring tissues was observed. The value of the 3D visualization technology for the preoperative assessment of liver autotransplantation for end-stage hepatic alveolar echinococcosis was assessed by comparing with the intraoperative findings. Results The 3D visualization reconstruction model clearly displayed the adjacent relationship between the lesions of end-stage hepatic alveolar echinococcosis and the neighboring tissues, and no significant difference was seen between the pre-resected liver volume in 3D visualization reconstruction model and the actually resected liver volume (t = 1.083, P > 0.05). Conclusions 3D visualization technology is feasible to develop a reasonable scheme for liver resection and vascular anastomosis for end-stage hepatic alveolar echinococcosis prior to liver autotransplantation, which may increase the success of surgery and improve the prognosis.

Lorlatinib: a third generation ALK inhibitor for treatment of non-small cell lung carcinoma / 药学学报

Lorlatinib (PF-06463922) is a highly selective and potent third generation anaplastic lymphoma kinase (ALK) inhibitor with dual activity against c-ros oncogene 1, a receptor tyrosine kinase (ROS1). In November 2018, the US Food and Drug Administration approved lorlatinib for treatment of disease progression in ALK-positive and late-stage NSCLC patients who receive the treatment with crizotinib and at least one of other ALK inhibitors; and those with disease progression after treatment of alectinib or ceritinib as the first ALK inhibitor. The results of phase I/II clinical trials showed that it has effective initial anti-tumor activity, strong intracranial therapeutic activity, with less tolerance and safety issues. This paper systematically reviewed the chemical structure, mechanism of action, pharmacodynamics, pharmacokinetics, usage and dosage, clinical research, safety and upcoming research fields of lolatinib, to provide an update on clinical or laboratory research and clinical practice.

Case-control study on minimally invasive surgery and conventional open plating for displaced midshaft clavicular fracture based on 3D-print / 中国骨伤

OBJECTIVE@#To compare clinical effect of minimally invasive surgery and conventional open plating for acute displaced midshaft clavicle fracture based on 3D-print.@*METHODS@#From July 2016 and December 2016, 40 patients with acute displaced midshaft clavicle fractures were retrospectively analyzed. The patients were divided into 3D minimally invasive surgery group (group A) and conventional open plating group (group B) according to different surgical incisions and whether to use 3D printing. In group A, including 11 males and 9 female, aged from 19 to 57 years old with an average of(37.2±9.3)years old; type 2A2 were 4 patients, type 2B1 were 9 patients and type 2B2 were 7 patients according to Robinson classification. In group B, including 13 males and 7 female, aged from 17 to 54 years old with an average of(35.1±9.5) years old; type 2A2 were 5 patients, type 2B1 were 8 patients and type 2B2 were 7 patients according to Robinson classification. Operative time, blood loss, length of incision, fracture healing time, complications were observed and compared between two groups, DASH score and Constant score of shoulder joint were evaluated at 12 months after operation.@*RESULTS@#Forty patients were followed up from 12 to 18 months with an average of(15.1±2.0) months. All fractures were healed, healing time in group A ranged from 12 to 18 months with an average of (14.3±1.7) months, in group B ranged from 11 to 18 months with an average of (14.4±1.9) months, while there was no statistical differences between two groups(>0.05). No differences in blood loss between two groups(>0.05). Operative time, length of incision in group A was less than that of group B (0.05). One patient in group A occurred complication, and 6 patients in group B occurred compilations, and has statistical differences between two groups(<0.05).@*CONCLUSIONS@#Minimally invasive technique based on 3D-print could resolve some difficulties of minimally invasive surgery effectively and achieve fracture healing and functional recovery similar to traditional open reduction with more beautiful incision, less complication, shorter operation time.

Value of three-dimensional visualization technology in preoperative evaluation of liver autotransplantation for end-stage hepatic alveolar echinococcosis / 中国血吸虫病防治杂志

Objective To evaluate the value of the three-dimensional visualization technology for the preoperative assessment of liver autotransplantation for end-stage hepatic alveolar echinococcosis. Methods A total of 8 patients with end-stage hepatic alveolar echinococcosis undergoing liver autotransplantation in Qinghai Provincial People’s Hospital from May 2013 to July 2017 were collected. All cases received preoperative abdominal CT scanning and dynamic three-phase enhanced CT scanning, and the original CT data were transferred to the human 3D visualization virtual surgical planning system. The volumes of Echinococcus multilocularis and pre-resected liver were measured using the 3D visualization reconstruction, and the relationship between the lesion and the neighboring tissues was observed. The value of the 3D visualization technology for the preoperative assessment of liver autotransplantation for end-stage hepatic alveolar echinococcosis was assessed by comparing with the intraoperative findings. Results The 3D visualization reconstruction model clearly displayed the adjacent relationship between the lesions of end-stage hepatic alveolar echinococcosis and the neighboring tissues, and no significant difference was seen between the pre-resected liver volume in 3D visualization reconstruction model and the actually resected liver volume (t = 1.083, P > 0.05). Conclusions 3D visualization technology is feasible to develop a reasonable scheme for liver resection and vascular anastomosis for end-stage hepatic alveolar echinococcosis prior to liver autotransplantation, which may increase the success of surgery and improve the prognosis.

Generation and identification of a mouse macrophage line lacking NLRP3 / 中国免疫学杂志

Objective:To establish a mouse macrophage line lacking NLRP3.Methods:A GFP and neomycin dual selection marker vector which contains an efficient shRNA-coding insert for mouse NLRP3,was constructed and transfected into macrophages (RAW264.7) to select the stable clone cells in G418-contained medium.Then,the expanded clone cells that retain strong GFP expression were further sorted using the popular flow cytometry.The obtained cell mix (herein termed RAWNKD) were passaged and maintained for further identification,including observation of GFP marker,especially quantitative PCR (RT-qPCR) to confirm knockdown of NLRP3 in the generated RAWNKD cells which were challenged with LPS and ATP or not.Results:Over 80% of RAWNKD cells expressed GFP,and little NLRP3 mRNA was detected in RAWNKD cells,notably no obvious increase in NLRP3 mRNA was observed when the RAWNKD cells were challenged by LPS and ATP.Conclusion:The macrophage line lacking NLRP3 was successfully established,and such macrophage deficient in NLRP3 inflammasome is a valuable cell model for investigating the activation of NLRP3 inflammasome,especially signaling in inflammation mediated by NLRP3 inflammasome.

Development of Tripterygium glycosides nano-carries based on "nanoemulsion-gels" and its pharmacodynamics / 中国中药杂志

The aim of this study is to develop the Tripterygium glycosides nanoemulsion gels and investigate its pharmacodynamics. Oleic acid was used as oil phase, polyoxyethylene castor oil as surfaetant, and 1,2-propanediol as cosurfactant to screen the formula of Tripterygium glycoside nanoemulsion using the pseudo-temary phase diagrams. Then the nanoemulsion gels was prepared. The ICR mouse ears were sensitazated by 7% DNCB, and then were excited by 0.3% DNCB to stimulate the model of mouse chronic dermatitis and eczema. The concentrations of IFN-γ, IL-4 and IL-8 in mouse blood were determined by ELISA. The results showed that Tripterygium glycosides nanoemulsion gels could significantly inhibit the swelling of mouse ears(P < 0.01) and ameliorate the edama and erythema of model mouse ears skin. Also it could significantly decrease the expression of IFN-γ and IL-4 in model mouse blood. Tripterygium glycosides nanoemulsion gels had a good therapeutic effect on mouse model of dermatitis and eczema. It was expected to provide a new and long-acting exterernal preparation for the treatment of dermatitis and eczema.

An evaluation of the inflammatory response of lipopolysaccharide-treated primary dental pulp cells with regard to calcium silicate-based cements / 国际口腔科学杂志·英文版

This study compared the biological changes of lipopolysaccharide (LPS)-treated dental pulp (DP) cells directly cultured on mineral trioxide aggregate (MTA) and calcium silicate (CS) cements. DP cells were treated with LPS for 24 h. Then, the LPS-treated DP cells were cultured on MTA or CS cements. Cell viability, cell death mechanism and interleukin (IL)-1β expressions were analysed. A one-way analysis of variance was used to evaluate the significance of the differences between the means. A significantly higher IL-1β expression (2.9-fold) was found for LPS-treated cells (P<0.05) compared with DP cells without LPS treatment at 24 h. Absorbance values of LPS-treated cells cultured on CS cement were higher than a tissue culture plate. A significant difference (P<0.05) in cell viability was observed between cells on CS and MTA cements 24 h after seeding. At 48 h, a high concentration of Si (5 mM) was released from MTA, which induced LPS-treated DP cell apoptosis. The present study demonstrates that CS cement is biocompatible with cultured LPS-treated DP cells. MTA stimulates inflammation in LPS-treated DP cells, which leads to greater IL-1β expression and apoptosis.

Comparison of internal fixation and semi-shoulder arthroplasty in treating proximal humerus comminuted fractures in elderly / 中国骨伤

<p><b>OBJECTIVE</b>To explore clinical effectiveness of internal fixation and semi-shoulder arthroplasty in treating proximal humerus comminuted fractures in elderly.</p><p><b>METHODS</b>From October 2009 and October 2011, 32 patients aged over 60 years old with three and four-part fractures of proximal humeral were treated with internal fixation (20 cases) and semi-shoulder arthroplasty (12 cases). In internal fixation group, there were 6 males and 14 females aged from 63 to 82 years old (ranged, 71.50 +/- 5.45), 8 cases with three-part fracture and 12 cases with four-part fracture, and treated with open reduction and locking plate internal fixation. While in semi-shoulder arthroplasty group, there were 4 males and 8 females aged from 61 to 85 years old (ranged, 72.80 +/- 6.80), 5 cases with three-part fracture and 7 cases with four-part fracture, and treated with semi-shoulder arthroplasty. Postoperative complications were observed, EQ-5D was used to evaluate quality of life, and Constant-Murley score was used to assess functional outcomes.</p><p><b>RESULTS</b>All patients were followed up from 12 to 24 months with an average of 18 months. All injuries were healed at stage I . Two cases in internal fixation group occurred severe complications, including 1 case with screw fracture, 1 case with avascular necrosis of humeral head. EQ-5D in interal fixation group and semi-shoulder arthroplasty group were respectively 0.65 +/- 0.12, 0.67 +/- 0.12, Constant-Murley score respectively was 63.20 +/- 11.35 and 66.80 +/- 11.96, and with no statistical meaning between two goups (P>0.05).</p><p><b>CONCLUSION</b>There is no difference in qulity of life and functional recovery for the treatment of proximal humerus comminuted fractures by open reduction and internal fixation and semi-shoulder arthroplasty. However, the complication rate in semi-shoulder arthroplasty was lower than that of internal fixation group.</p>

Effects of different mechanical ventilation methods on morphology of type Ⅱ alveolar epithelium cell in newborn piglets with acute lung injury / 中华实用儿科临床杂志

Objective To investigate the effects of 3 different ventilation methods,including conventional mechanical ventilation(CMV),high-frequency oscillatory ventilation(HFOV) and partial liquid ventilation(PLV),on the morphology of type Ⅱ alveolar epithelium cell (ACE Ⅱ) of newborn piglet with acute lung injury (ALI).Methods Twenty-four less than 3-day-old newborn piglets were enrolled.After ALI was established with saline lavage (38 ℃,0.035 L/kg),newborn piglets were randomly assigned to 4 study groups:control group(n =6,no ventilation),CMV group(n =6),HFOV group(n =6),and PLV group(n =6,38 ℃,0.018 L/kg).Piglets in the 4 groups were sacrificed after being ventilated for 24 hours,and the number,area,density of fluorescence of ACE Ⅱ were detected.Results Through 24 hours mechanical ventilation,the numbers of ACE Ⅱ in CMV group,HFOV group and PLV group remained were 30 ± 5,52 ± 5,81 ± 7,respectively,while areas of fluorescence were 340.40 ± 47.50,329.69 ± 124.50,295.55 ± 109.30,respectively,and there were significant differences among the 3 groups,and the population mean of density of fluorescence had significant difference among the 3 groups.The number of ACE Ⅱ remains was lowest in CMV group compared with HFOV group(P =0.026) and PLV group (P =0.000),and the density of fluorescence of ACE Ⅱ was lowest in CMV group compared with HFOV group (P =0.001) and PLV group (P =0.002).Conclusions Different mechanical ventilations have various effects for ACE Ⅱ,and CMV is the most harmful mechanical ventilation on ACE Ⅱ,while PLV is the least harmful.

Effects of mechanical ventilation method on inflammatory factors and pulmonary surfactant associated protein A of bronchoalveolar lavage fluid in newborn piglets with acute lung injury / 中华实用儿科临床杂志

Objective To investigate the effects of 3 different ventilation methods,including conventional mechanical ventilation (CMV),high frequency oscillatory ventilation(HFOV) and partial liquid ventilation (PLV),on the changes of inflammatory factors and pulmonary surfactant associated protein A (SP-A) in bronchoalveolar lavage fluid (BALF) in newborn piglets with acute lung injury(ALI).Methods Twenty-four newborn piglets,no more than 3 days old,were enrolled.After ALI made with saline lavage(38 ℃,35 mL/kg),newborn piglets were randomly assigned to 4 groups:control group (n =6,no ventilation),CMV group(n =6),HFOV group(n =6),and PLV group(n =6).Piglets were sacrificed after being ventilated for 24 h.Tumor necrosis factor-α (TNF-α),interleukin-8 (IL-8),interleukin-1 (IL-1) and SP-A in BALF were measured quantitatively by using enzyme-linked immunosorbent assay.Results In 3 groups using different ventilation methods,the population mean of TNF-o,IL-8,IL-1 and SP-A were statistically different (all P =0.000).SP-A in PLV group and HFOV group were higher than that in CMV group (all P ＜ 0.05),while IL-8,IL-1 and TNF-α in PLV group were lower than those in CMV group (all P ＜ 0.05),IL-8 and TNF-α in PLV group were lower than those in HFOV group (all P ＜ 0.05),IL-8 and TNF-α in HFOV group were lower than those in CMV group (all P ＜ 0.05).Conclusions Pulmonary inflammatory reaction was different in 3 ventilation groups.Compared with CMV and HFOV,PLV attenuated inflammatory reaction,so it could increase the expression of SP-A and decrease the degradation of SP-A.

Pharmacokinetics of the combined preparation of lisinopril and hydrochlorothiazide on Chinese healthy volunteers / 药学学报

The aim of the present study, performed on two different groups of volunteers, is to characterize the pharmacokinetics of lisinopril/hydrochlorothiazide combined tablet. After administration of high, medium and low doses of lisinopril/hydrochlorothiazide combined tablets, AUC and C(max) of two compounds both increase significantly with increase of dose. Neither normalized AUC/Dose nor C(max)/Dose has significant difference between every two tested dose groups. The similar results can be observed as for the parameters of t(max). Lisinopril and hydrochlorothiazide are both eliminated with linear characteristics. After repeated administration of lisinopril/hydrochlorothiazide combined tablets, AUC, C(max) and C(min) of lisinopril in the steady state increase. AUC and C(min) increase significantly. As for hydrochlorothiazide, AUC, C(max), C(min), and t(max) also increase in steady state. AUC and C(min) increase significantly. Administered with the test medication, lisinopril has an fluctuation index (FI) value of 2.29 and reaches a relative steady concentration. But hydrochlorothiazide has an FI value of 4.09 with relatively large fluctuating concentrations.

Changes of amino acids neurotransmitters in striatum of hemi-parkinsonian rhesus monkey after high frequency stimulation of subthalamic nucleus / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the influence of high frequency stimulation of the subthalamic nucleus on the levels of amino acids neurotransmitters in striatum of hemi-parkinsonian monkeys.</p><p><b>METHODS</b>Two rhesus monkeys were successfully prepared for the subsequent microdialysis sessions. Collecting the dialysate before turning on the pulse generator, and collecting at 1 week, 1, 8 and 12 months after high frequency stimulation of the subthalamic nucleus. The level of Glu, GABA and Tau were determined by high performance liquid chromatography and fluorometric detection (HPLC-FD).</p><p><b>RESULTS</b>After high frequency stimulation (HFS), PD symptoms of monkeys significantly improved. The levels of Glu in putamen and caudate nucleus of electrodes side at 1 week, 1, 8 and 12 months were increased significantly. The levels of GABA in putamen and caudate nucleus of electrodes side at 1 week, 1 month increased significantly compared with before turning on the pulse generator while decreased at 8, 12 months. The level of Tau in putamen and caudate nucleus increased significantly.</p><p><b>CONCLUSION</b>Long-term STN HFS can increase the level of glutamate and taurine, while decrease the level of GABA in putamen and caudate nucleus of electrodes side. It improves symptoms of hemi-parkinsonian rhesus monkey significantly.</p>