Research Progress in Pharmacology of Xiaoyaowan / 中国实验方剂学杂志

In traditional Chinese medicine， it is believed that the spleen is the foundation of acquired nature and the source of Qi and blood. All life activities of a person since birth depend on the water and grain essence transported by spleen and stomach. The liver helps the spleen to strengthen the movement， the liver and spleen cooperate with each other. The liver and the spleen are invigorated， so that the Qi and blood are sufficient. The external energy can nourish the limbs， muscles and fur. The Qi and blood can be supplied to the internal organs， meridians and bones， and the body can be nourished both inside and outside to strengthen the acquired foundation. Emotional dissatisfaction can lead to stagnation of liver Qi， loss of spleen Qi， failure to dredge Qi， and deficiency of spleen Qi， forming the syndrome of liver depression and spleen deficiency. Its clinical manifestations include the symptoms of liver Qi stagnation such as depression， stamina， and chest fullness， as well as symptoms of spleen deficiency such as anorexia， abdominal distension， loose stools. Xiaoyaowan is an effective classic prescription for the treatment of liver stagnation and spleen deficiency syndrome， which is based on the dosage form of Xiaoyaosan in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It has the effect of relieving depression， nourishing blood and invigorating spleen. In modern research， it has been found that Xiaoyaowan has good curative effect in the treatment of endocrine diseases， liver diseases， immune diseases， and neurological diseases， etc. It was praised by the famous medical scientist YE Tian-shi in the Qing Dynasty as "the holy medicine for women"， with a wide range of significant curative effects gynecology. Progress has been also made in pharmacological research. In this article， we have searched and consulted the relevant literature reports of Xiaoyaowan in recent years， summarized the key directions of the pharmacological research literature， and proposed deficiencies to provide relevant basis for the in-depth study of Xiaoyao pill in the future.

Association Between the Circumferential Pulmonary Veins Scar and Atrial Fibrillation Recurrence in Patients Undergoing Catheter Ablation of Atrial Fibrillation / 中国循环杂志

Objectives: This study aims to analyze the relationship between late gadolinium enhancement cardiac magnetic resonance imaging (LGE-cMRI) detected scar formation of circumferential pulmonary vein and recurrence rate after catheter ablation in patients with atrial fibrillation, and to compare the efficacy of the single-step cryoballoon ablation with the point-by-point radiofrequency current ablation. Methods: A total of 56 patients with nonvalvular atrial fibrillation who underwent catheter ablation from July 2014 to December 2016 in Fujian Provincial Hospital were enrolled in this study. Among them, 27 patients underwent radiofrequency ablation (RFA), and 29 cases underwent cryoballoon ablation (CBA). Scar formation of circumferential pulmonary vein was detected by LGE-cMRI in all patients at 3 months after ablation. All patients were monitored by telephone or outpatient follow-up (patients complaint, ECG or 24-hour Holter, etc.) at 6 months post ablation. Recurrent atrial tachyarrhythmias were defined as ≥ 30 seconds AF, atrial flutter, or atrial tachycardia. Results: AF recurrence was defined in 13 (23.21%) patients. The ratio of scar formation in circumferential pulmonary vein was significantly lower in recurrence patients than that in the non-recurrent patients ([63.23±5.86]% vs [79.95±7.47]%, P<0.001). The ratio of scar formation in each pulmonary vein of 56 patients was as follows: (76.80±11.60)% in the left superior pulmonary vein, (78.90±10.64)% in the left inferior pulmonary vein, (83.35±9.44)% in the right superior pulmonary vein (P<0.05 vs the left superior pulmonary vein), which was significantly lower in the right inferior pulmonary vein (66.13±13.44)% than above veins (all P<0.05). The ratio of scar formation of all four pulmonary vein was significantly lower in recurrence patients than in the non-recurrent patients, especially in left superior pulmonary vein ([61.19±4.89]% vs [81.52±8.43]%) and the right lower pulmonary vein ([52.47±7.62] % vs [70.26±12.03]%), both P<0.001.Univariate analysis showed that the recurrence rate , the total ratio of scar formation in circumferential pulmonary vein and the ratio of scar formation in recurrence patients were similar between the CBA group and the RFA group. Conclusions: Lower circumferential pulmonary vein scar is associated with higher recurrence rate post catheter ablation in atrial fibrillation patients. The scar formation ratio is low in the right inferior pulmonary vein and the left superior pulmonary vein. The circumferential pulmonary veins scar after cryoablation and radiofrequency catheter ablation is equivalent, indicating the pulmonary vein isolation efficacy of the two procedual methods is comparable.

Effects of melatonin combined with Cis-platinum or methotrexate on the proliferation of osteosarcoma cell line SaOS-2 / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effects of melatonin (Mel) combined with cis-platinum (DDP) or methotrexate (MTX) on the proliferation of osteosarcoma cell line SaOS-2, and to explore whether Mel combined with DDP or MTX could play a synergistic antitumor effect.</p><p><b>METHODS</b>SaOS-2 was treated with Mel alone or Mel combined with DDP or MTX. Cell counting kit-8 assay was used to measure the cell activities. Combination index(CI) value was used to evaluate the combined effects: CI<1 indicating synergetic effect, CI=1 additive, and CI>1 antagonistic.Flow cytometry was used to analyze cell cycle distribution and cell apoptosis.</p><p><b>RESULTS</b>After treated with Mel (0.5,1,2,4,5 mmol/L), DDP (6.67, 16.67, 33.33, 66.66 μmol/L) or MTX(0.1, 0.5, 1, 2, 4 mmol/L)alone,SaOS-2 cell activities decreased in a dose-dependent manner (all P<0.05). The activities of SaOS-2 cell treated with both Mel (1 mmol/L) and DDP or MTX were significantly lower than that of DDP or MTX alone (all P<0.05).CI values of cells exposed to 1 mmol/L Mel plus 6.67, 16.67, 33.33, and 66.66 μmol/L DDP were 1.18, 1.21, 1.09, and 0.84, respectively,and CI values of cells exposed to 1 mmol/L Mel plus 0.1, 0.5, 1, 2, and 4 mmol/L MTX were 0.88, 0.88 ,0.83, 0.78, and 0.81, respectively. The G1-stage cells were increased and the S-stage cells were reduced when the cells were treated with Mel (1 mmol/L) alone or combined with MTX (0.5 mmol/L) (P<0.05). The S-stage cells were increased when the cells treated with MTX (0.5 mmol/L) (P<0.05). The apoptotic cells were increased when they treated with Mel (1 mmol/L) alone or combined with DDP (16.67 μmol/L) or MTX (0.5 mmol/L) (P<0.05). When the cells were treated with Mel combined with DDP or MTX, the apoptotic cells were more than that of DDP or Mel alone(P<0.05).</p><p><b>CONCLUSIONS</b>Mel can inhibit SaOS-2 cells activity,block the cell cycle at G1-stage,and induce apoptosis. Mel has an antagonistic effect with lower concentration of DDP but a synergistic effect with MTX or higher concentration of DDP.</p>

Treatment of thoracolumbar tumors with total en bloc spondylectomy and the results of spinal stability reconstruction / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effect of total en bloc spondylectomy (TES) for thoracolumbar tumors and the results of spinal stability reconstruction.</p><p><b>METHODS</b>From January 2007 to June 2011 there were 18 patients with thoracolumbar tumors distributed in the thoracic vertebrae (n = 10) and lumbar vertebrae (n = 8). There were 7 haemangiomas, 5 giant cell tumors of bone, 1 malignant schwannoma, 1 solitary plasmocytoma, 1 neuroblastoma, 1 osteoblastoma, 1 metastatic malignant fibrous histiocytoma, and 1 metastasis of breast cancer. All the 18 patients were treated with improved TES under electrophysiological monitoring of spinal cord. Four patients were treated through one-stage combined anteroposterior approach and 14 patients through one-stage posterior approach. The anterior reconstructions included titanium mesh cages filled with bone or bone cement in 15 cases, titanium mesh cage with strengthened rings in 2 cases and artificial vertebral body replacement in 1 case. The posterior reconstruction included multiple segmental fixation with pedicle screw-rod system in 15 cases and short segmental fixation in 3 cases. Massive bone auto-graft was employed in 13 cases and fragmental bone graft in 5 cases.</p><p><b>RESULTS</b>The total en bloc spondylectomy was performed successfully in 15 patients and unsuccessful in 3 whose spinal tumors were resected by piecemeal technique. In 15 patients with successfully performed TES, the duration of surgery was from 340 to 610 min (average, 450.7 min), the blood loss was from 3000 to 10 200 ml (average, 4850 ml), and the intraoperative blood transfusion was from 2800 to 9600 ml (average, 4200 ml). The operation-related complications comprised hemopneumothorax, intercostal nerve pain, stress ulcer and bleeding, and so on. One year after operation, the patients with neurological dysfunction recovered from grade A to grade D in one patient, and to grade E in the other 14 cases. The average visual analog scale (VAS) scores was 0.5. One patient with plasmacytoma and another one with L5 metastatic tumor suffered progression of the disease and were living with the diseases. The patient with metastatic malignant fibrous histiocytoma died of local recurrence and lung metastasis 16 months postoperatively. One patient with L4 neuroblastoma died of other reason and all the rest were free from relapse. The Cobb angle of upper and lower vertebral body adjacent to the involved vertebrae in sagittal plane was from -26.7° to 12.0° (average, -2.57°) just postoperatively and from -17.5° to 57.2° (average, 11.5°) at the last follow-up or before reoperation. There were 2 patients with screw-rod breakdown and 2 patients with internal fixation loosening. The measurement of titanium mesh cage subsided into adjacent vertebral bodies was average 7.5 mm. The revision surgery was performed in 3 patients, through combined anteroposterior approach in 2 and only posterior approach in 1 patient.</p><p><b>CONCLUSIONS</b>TES significantly increases the therapeutic effect of spinal tumors, although accompanied with high difficulty and massive bleeding. In spinal stability reconstruction after total spondylectomy, it should be emphasized that posterior long segment fixation with pedicle screw-rod system, massive bone bridging graft and the application of thoracolumbosacral orthosis can achieve short-term firm fixation and long-term fusion-stabilization.</p>

Analysis of curative effect for 21 recurrent soft-tissue sarcoma / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the effect of the surgery for recurrent soft-tissue sarcoma, and evaluate the treatment strategies.</p><p><b>METHODS</b>The curative effect of 21 cases of recurrent soft-tissue sarcomas from January 2005 to March 2011 is analyzed.</p><p><b>RESULTS</b>In 21 cases, 7 cases were amputated, 12 cases were ampliative resection and 2 cases were marginal excision. The 4 cases were recurrent, metastasis and dead, 1 cases were recurrent and live with tumor, 1 cases had metastasis and live with tumor.</p><p><b>CONCLUSIONS</b>Appropriate enough surgery margine can prevent the local recurrence, and complete removal of the tumor and comprehensive radiation and chemotherapy treatment of recurrent soft tissue tumor is the key to success.</p>

Release kinetics of methotrexate loaded calcium phosphate cement and histological evaluation of the osteogenesis in rabbits / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the release kinetics of methotrexate-loaded calcium phosphate cement (MTX-CPC) implanted in vivo and histologically investigate its resorption and osteogenesis.</p><p><b>METHODS</b>MTX-CPC consisting of 1% methotrexate (MTX) (weight/weight) was pre-set and implanted into femoral muscles of 24 New Zealand rabbits. The in vivo MTX release kinetics was determined on the 1st, 2nd, 5th, 10th, 15th, 20th, 25th, and 30th post-implantation day. The local concentrations and the residual percentage of MTX were determined. Then the pre-set MTX-CPC was implanted into femoral condyle. Calcium phosphate cement (CPC) without MTX was used as a control. The femurs were harvested at the 1st day and the 1st, 3rd, and 6th month and examined by X ray. Then histomorphometric analyses including percentage of newly formed bone and amount of osteoblast and osteoclast were performed.</p><p><b>RESULTS</b>The MTX release kinetics in vivo confirmed that MTX-CPC was a monolithic matrix system, with a burst effect in the initial stage and a sudden drop thereafter. The local concentration of the released MTX was 0.372 μg/ml on the 30th post-implantation day; with a concentration higher than the effective concentration,the incorporated MTX was expected to be continuously released over the following 2-3 months. Both MTX-CPC and CPC showed good biodegradability and osteoconduction. Although the release of MTX had an inhibitory effect on osteogenesis, especially in the initial stage, the area of newly formed bone, the amount of osteoblasts, and the amount of osteoclasts were not significantly different between MTX-CPC group and CPC group on the 6th post-implantation month.</p><p><b>CONCLUSIONS</b>MPX-CPC system is an effective drug delivery system. Both MTX-CPC and CPC has good biodegradability and osteoconduction. Therefore,MTX-CPC system can be an ideal material for filling defects and controlling local recurrence.</p>

Relationship between atrial fibroblast proliferation/fibrosis and atrial fibrillation in patients with rheumatic heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between gene expressions of basic fibroblast growth factor (bFGF), smooth muscle alpha-actin (alpha-SMA) and proliferating cell nuclear antigen (PCNA) and atrial fibrosis in patients with atrial fibrillation (AF).</p><p><b>METHODS</b>The right atrial tissue samples were taken from 75 patients with rheumatic heart disease underwent heart valve replacement surgery (34 patients with sinus rhythm, 11 patients with paroxysmal AF and 30 patients with persistent AF) and stained with picrosirius red for quantitative analysis of collagen accumulation. The mRNA and protein levels of bFGF, alpha-SMA and PCNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical technique, respectively.</p><p><b>RESULTS</b>The percent volume fraction of collagen (CVF) was the highest in persistent AF group and the lowest in the sinus rhythm group (all P < 0.01). CVF significantly correlated with AF duration (r = 0.390, P = 0.010) and left atria (LA) dimension (r = 0.320, P = 0.005). The mRNA and protein levels of bFGF, alpha-SMA and PCNA were significantly higher in the persistent AF group than those in the paroxysmal AF group (all P < 0.05) and significantly higher in both AF groups than those in the sinus rhythm group (P < 0.05-0.01). The mRNA and protein levels of bFGF were positively correlated with CVF (r = 0.330, P = 0.004 and r = 0.292, P = 0.013, respectively), AF duration (r = 0.330, P = 0.005 and r = 0.299, P = 0.010, respectively) and left atrial dimension (r = 0.342, P = 0.003 and r = 0.285, P = 0.015, respectively).</p><p><b>CONCLUSION</b>The increased gene expressions of bFGF, alpha-SMA and PCNA in atrium during AF may contribute to atrial fibrosis by promoting fibroblast proliferation in AF patients.</p>

Development of a novel drug dilivery system based on calcium phosphate cement with methotrexate and its drug release test in vitro / 中国医学科学院学报

<p><b>OBJECTIVE</b>To develop a novel drug dilivery system based on calcium phosphate cement (CPC) with methotrexate (MTX) as a model drug and to study its drug release in vitro.</p><p><b>METHODS</b>Three MTX mass fractions (0.1%, 0.2%, and 0.5%) were tested after solidification, and the compound of CPC-MTX were put into the simulated body fluid at 37 degrees C. The concentration of MTX was tested by high-performance liquid chromatography at day 2, 5, 10, 16 hours, 1, 2, 3, 5, 8, 10, 15, 20, 25, 30, 35, 40, and 45 days. The drug dilivery curves were drawn and drug dilivery rules were analyzed.</p><p><b>RESULTS</b>MTX was released slowly and stably from the compound of CPC-MTX. Remarked prophase of drug release was noted, which conformed with the Higuchi equation. The drug release rate and concentration was related with the concentration of MTX in compound but not with the thickness and shape of CPC. The releasing time was not affected by the concentration of MTX.</p><p><b>CONCLUSION</b>A stable drug dilivery system can be developed by loading proper concentration of MTX into CPC.</p>

Application of the proximal tibiofibular joint resection on the limb salvage for osteosarcoma of the proximal tibia / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the proximal tibiofibular joint resection on the limb salvage for osteosarcoma of the proximal tibia.</p><p><b>METHODS</b>Between August 1995 and January 2004, 11 patients with osteosarcoma of proximal tibia and tibiofibular joint involved underwent resection and endoprosthetic proximal tibial replacement. Seven patients were male and 4 were female. The patients ranged in age from 14 to 23 years (mean 18 years). The surgical stage were IIB.</p><p><b>RESULTS</b>The follow-up period varied from 2 to 9 years (mean 59 months). Three patients died of pulmonary metastases, 1 patient was still alive with pulmonary metastasis, 1 patient underwent amputation for local recurrence. There was 1 early skin necrosis, 2 transient palsy of the common peroneal nerve, and 2 thrombus of lower limb vein. The mean postoperative Musculoskeletal Tumor Society score of the knee joint was 70% (range 55% - 86%), the mean postoperative range of motion was 85 degrees (range 0 degrees - 120 degrees ), and the extensor lag varied from 0 degrees to 20 degrees .</p><p><b>CONCLUSIONS</b>Limb salvage for osteosarcoma of the proximal tibia with proximal tibiofibular joint resection and custom-made prosthesis reconstruction has had excellent results, however, the prevention and treatment of relevant complications should be given more attention.</p>

Efficacy and safety evaluation of glucosamine hydrochloride in the treatment of osteoarthritis / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of glucosamine hydrochloride for the treatment of osteoarthritis.</p><p><b>METHODS</b>A multi-central, randomized, controlled clinical trial of glucosamine hydrochloride comparing glucosamine sulfate for the treatment of osteoarthritis was performed. One hundred and forty-three patients suffering from knee or hip osteoarthritis were randomized into study (glucosamine hydrochloride) or control (glucosamine sulfate) group. Patients in study group orally took glucosamine hydrochloride 2 times daily for 6 weeks, each time 1 capsule, and those in control group took glucosamine sulfate 3 times daily for 6 weeks also, each time 2 capsules.</p><p><b>RESULTS</b>The symptomatic improvement of joint pain at walking, at rest and stiffness after 6 week treatment with glucosamine hydrochloride was better than those with glucosamine sulfate. The results had significant difference (P < 0.05). Total effective rates of patients with glucosamine hydrochloride was 75.4% and 60.6% with glucosamine sulfate, but no statistical difference. The results suggested both glucosamine had the considerable efficacy in the treatment of osteoarthritis. Three cases in study group and 2 in control group reported mild adverse events. No severe adverse events (SAE) was observed.</p><p><b>CONCLUSION</b>Glucosamine hydrochloride is as effective and safe as glucosamine sulfate for the treatment of osteoarthritis.</p>