Tianma Gouteng granules decreases the susceptibility of Parkinson's disease by inhibiting ALOX15-mediated lipid peroxidation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tianma Gouteng granules (TG), a clinical prescription of traditional Chinese medicine, has been clinically applied to treat Parkinson's disease (PD) in combination with Madopar, as included in the Chinese Pharmacopoeia (2015). TG has the potential to decrease the susceptibility of PD pharmacologically, however the mechanisms need detailed demonstration. AIM OF THE STUDY: To evaluate the pharmacological activities, as well as the possible mechanism of TG in diverse models of PD. MATERIALS AND METHODS: 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice, were utilized as PD animal models. Rotarod, locomotor activity, inclined plane and traction tests were used for behavioral assessment. Immunohistochemistry was used for tyrosine hydrolase determination. Western blot were conducted for detection of 4-HNE and 15-lipoxygenase-1 (ALOX15). The interactions of ALOX15 with the components in TG were predicted by molecular docking approach. RESULTS: Lipid peroxidation was involved in dopaminergic neuron damage in 6-OHDA-induced rat models. In MPTP-treated mice, the inhibition of lipid peroxidation improved behavioral and pathological symptoms of PD. The lipid peroxidation-related protein, ALOX15 was found to be the key factor in PD process in diverse PD models including 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice. TG treatment significantly relieved behavioral and pathological symptoms of MPTP-induced PD mouse models with a potential mechanism of alleviating ALOX15-induced lipid peroxidation. Moreover, the results of molecular docking analysis show that compounds in TG might have interactions with ALOX15. CONCLUSIONS: TG effectively improved the behavioral and dopaminergic neuron damage in diverse PD models. The mechanism of this action may be related to the direct inhibition of ALOX15 and the relief of lipid peroxidation.

Clinical Prescription-Protein-Small Molecule-Disease Strategy (CPSD), A New Strategy for Chinese Medicine Development: A Case Study in Cardiovascular Diseases.

Chinese medicine is a national treasure that has been passed down for thousands of years in China. According to the statistics of the World Health Organization, there are currently four billion people in the world who use Chinese medicine to treat diseases, accounting for 80% of the world's total population. However, the obscurity of its theory, its unmanageable quality, its complex compositions, and the unknown effective substances and mechanisms are great obstacles to the internationalization of Chinese medicine. Here, we propose a new strategy for the development of Chinese medicine: the clinical prescription (C)-protein (P)-small-molecule (S)-disease (D) strategy, namely the CPSD strategy. The strategy uses clinical prescriptions as the source of medicine and uses computer simulation technology to find small-molecule drugs targeting therapeutic proteins for treating specific diseases so as to deepen awareness of the value of Chinese medicine. At the same time, this article takes cardiovascular drug development as an example to introduce the application of CPSD, which will be instrumental in the further development, modernization, and internationalization of Chinese medicine.

[Trace phenolic compounds from Red Yeast Rice].

Trace chemical constituents from the ethyl acetate extract of Red Yeast Rice were investigated. Four phenolic compounds were isolated by various column chromatographies, and their structures were identified on the basis of spectroscopic analysis including UV, MS, IR and NMR. The four compounds were identified as 2-methyl-5-(2'R-methyl-4'-hydroxy-butyl)-cinnamic acid(1), 5-(2'-hydroxy-6'-methyl phenyl)-3-methylfuran-2-carboxylic acid(2), daidzein(3), and genistein(4). Compound 1 was new and 2 was firstly discovered from the genus Monascus, while 3-4 were obtained from Red Yeast Rice for the first time.

Less wound complications of a sinus tarsi approach compared to an extended lateral approach for the treatment of displaced intraarticular calcaneal fracture: A randomized clinical trial in 64 patients.

BACKGROUND: We conducted a prospective randomized clinical trial to compare the clinical and radiological outcomes of the sinus tarsi and extended lateral approaches for the surgical treatment of displaced intraarticular calcaneal fractures. METHODS: Between January 2009 and January 2014, patients with displaced intraarticular calcaneal fracture were randomly assigned to receive surgical treatment by the sinus tarsi approach or the extended lateral approach using block randomization. We recorded and analyzed data on demographics, time to surgery, wound complications, Böhler angles pre- and postoperatively, and American Orthopedic Foot & Ankle Society score. RESULTS: Sixty-four patients met the inclusion criteria and were randomly assigned to the 2 groups: 32 patients underwent sinus tarsi approach, and 32 patients the extended lateral approach. Baseline characteristics of both groups were similar. The time to surgery in the sinus tarsi approach group was significantly shorter than in the extended lateral approach group (P = 0.04). The wound complication rates were 6.3% and 31.2% in the sinus tarsi approach and extended lateral approach groups, respectively, which was significantly different (P = 0.01). Regarding the clinical outcomes, the groups did not differ significantly on walking visual analogue scale or American Orthopedic Foot & Ankle Society scores at 6 months and 1 year postoperatively. No significant differences existed between groups regarding the Böhler angle at different times and reduction quality of the articular surface and the medial wall. CONCLUSION: Compared with the extended lateral approach, the sinus tarsi approach decreased wound complications and preoperative waiting time, and achieved similar functional and radiological outcomes for displaced intraarticular calcaneal fractures.

Plasminogen is a critical regulator of cutaneous wound healing.

Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogen-deficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chronic inflammation. Delayed formation of granulation tissue suggests that fibroblast function is impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for subsequent steps, including resolution of inflammation and activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing process that is comparable to that in wild-type mice. Besides of being an activator of the inflammatory phase during wound healing, plasminogen is also required for the subsequent termination of inflammation. Based on these results, we propose that plasminogen may be an important future therapeutic agent for wound treatment.

[Reconstruction intramedullary nailing for treatment of ispsilateral femoral neck and shaft fractures].

OBJECTIVE: To evaluate the curative effect and surigical skills of reconstruction intramedullary nailing in the treatment of ipsilateral femoral neck and shaft fractures. METHODS: From January 2007 to January 2013, 13 patients with ipsilateral femoral neck and shaft fractures were treated by reconstruction intramedullary nailing including 11 males and 2 females with an average age of 38.9 yeas old ranging from 25 to 53 years old. For femoral neck fractures,10 cases were basilar neck fracture, 3 were transcervical fractures and according to Garden classification,10 were type II, 2 were type III and 1 was type IV. For feormal shaft fracture, 5 were type I, 4 were type II, 3 were type III and 1 was type IV according to Winquist classification. The location of all 13 feormal shaft fractures were all in the uper 3/4 of the feormal shaft. Complications and postoperative function were recorded and evaluated. RESULTS: Eleven patients were followed up for 23.45 months (12 to 36 months). Time from injury to operation was 5.9 days in average. Malunion of femoral neck fracture happened in 1 patient, nonunion of femoral shaft fracture happened in 2 patients. NO femoral head osteonecrosis, infection and malunion of femoral shaft fracture happened. According to Friedman-Wyman classification, 8 cases get good result, 2 get faii and 1 get poor. CONCLUSION: Reconstruction intramedullary nailing is a good choice for the ipsilateral femoral neck and shaft fractures with the advantages of less soft-tissue trauma and complications.

[Case-control studies on clinical effects of non- and remnant preservation for reconstruction of posterior cruciate ligament].

OBJECTIVE: To evaluate the methods and therapeutic effects of the posterior cruciate ligament (PCL) reconstruction with remnant preservation and no preservation. METHODS: From January 2006 to January 2011,45 patients received arthroscopic PCL reconstruction by using hamstring tendon autograft fixed with bioabsorbable interference screw. Twenty-five patients were treated with PCL reconstruction with remnant no preservation, including 19 males and 6 females. During the operation, remnant PCL was not preserved, double-screws and whole-bone-tunnel technique was used to fix the tibial side. Twenty patients were treated with PCL reconstruction with remnant preservation, including 15 males and 5 females. Although the fixation technique was similar to the remnant no preservation group, the remnant was preserved. All the patients were followed up with a mean period of 18 months. Each patient was evaluated using the following variables: posterior laxity on KT-2000, Lysholm knee score, International Knee Documentation Committee (IKDC) knee score and grade. RESULTS: At the latest follow-up, the results of mean side-to-side differences in posterior tibial translation, Lysholm knee score and IKDC score were (4.2 +/- 2.1) mm, 84.3 +/- 10.5 and 64.5 +/- 8.8 in the remnant no preservation group separately, and (3.9 +/- 1.8) mm, 86.5+/- 8.9 and 68.6 +/- 7.9 in the remnant preservation group separately. There were no statistical differences of above results between the two groups. However, IKDC objective grade differed significantly between the two groups and the result in remnant preservation group was better than that of remnant no preservation group. CONCLUSION: Remnant preservation in PCL reconstruction can provide better activity-related outcomes than remnant no preservation.

[Minimally invasive percutanuous cannulated pedicle screw system fixation for the treatment of thoracolumbar flexion-distraction fracture without neurologic impairment].

OBJECTIVE: To explore the feasibility and effect of percutanuous cannulated pedicle screw AF system fixation for the treatment of thoracolumbar flexion-distraction fracture without neurologic impairment. METHODS: From June 2008 to June 2010,21 patients with thoracolumbar flexion-distraction fracture were treated with percutanuous cannulated pedicle screw fixation. There were 16 males and 5 females with the mean age of 32.7 years ranging from 23 to 55 years. Injured levels 5 cases was in T12, 13 was in L1, 3 was in L2. According to classification of AO, B1 was in 13 cases, B2 was in 8 cases. ASIA grade of all the patients were grade E. The mean operative time, bleeding volume, lengths of stay were evaluated. All the patients took the X-ray and three-dimensional CT reconstruction to observe the fracture healing and to measure the height of the anterior border of fracture vertebral body and the Cobb angle of kyphosis. The visual analogue scales (VAS) were compared preoperation and postoperation. The clinical effects were analyzed according to Oswestry Disability Index (ODI) from 10 aspects, including pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, traveling. RESULTS: All the operations were successful and the mean time was (109.0+/-16.0) min, blood loss was (90.0+/-15.0) ml, lengths of stay was (7.7+/-2.3) d. No postoperative neurological deficits or wound infection occured. One case occurred subcutaneous fluid of incision and 1 case occurred delayed healing of incision. Fifteen patients were followed up with an average of 16.7 months (12-33 months). The VAS score improved from preoperative 8.3+/-1.7 to 1.8+/-1.2 at final follow up (P<0.05). The ODI of last follow-up was (10.0+/-1.2)%. Three-dimensional CT reconstructions and X-rays showed the height of vertebral body increased from preoperative (54.0+/-17.1)% to (82.7 - 3.5)% at 12 months after operation (P<0.05). Cobb angle of kyphosis changed from preoperative (23.0+/-13.1) to (6.9+/-5.1) degrees at 12 months after operation (P<0.05). The healing time of fracture was (4.7+/-0.3) months. There were no significant loss of vertebral height or kyphosis correction between postoperative 1 months and last follow-up (P>0.05). There were satisfactory fracture reduction and good position of internal fixation,and no loss of reduction within 12 months and no fixation failure in follow-up. CONCLUSION: The minimally invasive percutaneous cannulated pedicle screw fixation technique is feasible in treatment of thoracolumbar flexion-distraction fracture without neurologic impairment. This technique can avoid re -injury of posterior ligaments and bone structure, and may rebuild posterior tension band structure with the advantages of less trauma, less bleeding,shorter operative time, rapid postoperative recovery and so on.

[The value of modified POSSUM scoring system in predicting mortality and morbidity for the intertrochanteric fracture in elder patients].

OBJECTIVE: To evaluate the value of modified physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) scoring system in predicting mortality and morbidity for the intertrochanteric fracture in elder patients. METHODS: A retrospective study was conducted over a period of nearly 2 years from January 2007 to December 2008. Complete data from 119 patients were analyzed to compare the mortality and morbidity predicted by the POSSUM and the observed mortality and morbidity. POSSUM risk was calculated using the original POSSUM equation. RESULTS: POSSUM predicted 11(9.2%) deaths, which had no statistical significance with the observed mortality 5 (4.2%) (chi² = 2.412, P = 0.120). The estimated incidence of postoperative complications was 42 (35.3%), which also has no statistical significance with the observed morbidity 39 (32.8%) (chi² = 0.168, P = 0.682). CONCLUSIONS: The modified POSSUM scoring system can predict accurately postoperative mortality and morbidity for the patients underwent intertrochanteric fracture and it predict more accurately in high risk band. The physiological score can be used to evaluate the physiological conditions preoperative and the pulmonary disease is the most important factor lead to death of the elder patients underwent intertrochanteric fracture.

[Biomechanical study and clinical application of cannulated compression screws with across solid frame for intertrochanteric fractures].

OBJECTIVE: To evaluate the safety and efficiency of treating the senile intertrochanteric fractures with cannulated compression screws (CCS) with across solid frame in femur head via biomechanical tests and clinical application. METHODS: Biomechanical tests: the fracture model was made in 31-A1.3 style, 6 pairs of flesh and embalmed cadaveric femurs were mechanically tested in a single-limb stance configuration. A material testing machine was used to apply vertical loads onto the femoral head. Both stiffness and reverse turn were recorded. Clinical application: from 1998 to 2006, According to damage control orthopedics (DCO) and American Society of Anesthesiologists (ASA) and the Evans classification, 51 patients received treatment with CCS with across solid flame in femur head. All the cases were followed up for 12 to 36 months (mean: 18 months). RESULTS: the differences between two groups in BMD (bone mineral density) were of statistical significance. And tensile rigidity and torsional rigidity of CCS were strong enough to bear weight. The CCS group had a lesser amount of blood loss or transfusion and lower treatment expenses. CONCLUSION: Cannulated compression screw with across solid flame is strong enough to be employed as an effective method to treat aged intertrochanteric hip fractures with the advantages of simple procedure, minimal invasion, stable fixation and weight bearing.