Objective To study the influence of aldehydes and tannic acid on soft capsules, approach how to prevent soft capsules from delayed disintegration. Methods Add aldehydes and tannic acid to soft capsules material ingredient, to proceed accelerating stability trial and test the disintegration time. Result Little increase of aldehydes amount had great effect on the disintegration time of soft capsules, different aldehydes and tannic acid had different effect on the disintegration time, adding some organic acid such as fumaric acid to the material would improve disintegrating property. Conclusion The amount of aldehydes and tannic acid contained in the material and ingredient should be controlled strictly when prepare soft capsules so that the disintegration time of capsules could be complying with the Pharmacopeia.

Objective To evaluate effection of Milrinone in patients with pneumocardial disease at acute exacerbation stage .Methods Eighty-three patients were randomly divided into two groups , both in the same conventional therapy , the treatment group received 10mg of Milrinone dissolve in 250ml 5% glu-cose intravenous infusion , 1 second /day, 10 days for a course of treatment .Observation group were treated with 5%glucose infusion 250ml, 1 time /day.The arterial blood gas, echocardiography measurements with mean pulmonary artery pressure , left ventricular ejection fraction and clinical evaluation to improve cardiop-ulmonary function efficiently were compared before and after treatment .Results Arterial blood gas analy-sis, pulmonary artery pressure and left ventricular function were improved and comprehensive evaluation of the efficiency of cardiopulmonary function in treatment group were significantly better than the control group ( Pall<0.05).Conclusion There is satisfactory of Milrinone in acute exacerbation of chronic pulmonary heart disease .

OBJECTIVE: To establish HPLC method for the determination of the contents of atenolol, hydrochlorothiazide and nifedipine in xueyaan sustained release tablets. METHODS: The determination was performed on ZORBAX SB C18 column with column temperature at 35℃ . The mobile phase consisted of 0. 01mol? L- 1 sodium dihydrogen phosphate solution- methanol- acetonitrile ( 6∶ 3∶ 1) . The UV detection wavelength was set at 272nm and the sample size was 20? L. RESULTS: The liner ranges of atenolol, hydrochlorothiazide and nifedipine were 10～ 250? g? mL- 1 ( r=0. 999 4) , 6～ 150? g? mL- 1( r=0. 999 6) , and 5～ 125? g? mL- 1( r=0. 999 2) respectively. The average recovery rates of the three constituents were ( 98. 51? 0. 98) % ～ ( 99. 12? 0. 98) % , ( 98. 87? 1. 10) % ～ ( 99. 69? 1. 43) % , and( 98. 80? 1. 27) % ～ ( 99. 38? 1. 13) % , respectively, with RSD at 1. 00% , 1. 17% , and 1. 25% , respectively. CONCLUSION: The established method is simple, sensitive and reproducible, and suitable for the quality control of xueyaan sustained release tablets.

Objective To explore the mechanism of 125I seed interstitial implantation-induced apoptosis of liver VX2 tumor cells in experimental rabbits, and to compare the effects of different radioactivity 125I seeds on the apoptosis and on the proliferation of tumor cells. Methods A total of 24 rabbit models with VX2 liver cancer were randomly and equally divided into 3 groups, and 125I seeds with different initial radioactivity were separately implanted into the rabbits of the three groups. 125I seeds of 0 mCi radioactivity were used in the control group (n=8), 125I seeds of 0.7 mCi radioactivity were used in the 0.7 mCi group (n=8) and 125I seeds of 1.0 mCi radioactivity were used in the 1.0 mCi group (n=8). The experimental rabbits were sacrificed at 5 weeks after the implantation; the tumor lesions were removed, and the effects of 125I seeds on the apoptosis and proliferation of tumor cells were determined. The tumor cell apoptosis rate, tumor growth-related factors, tumor growth factor expression protein and the influence of caspase-3 activity were evaluated. Results Regardless of their initial radioactivity, all the 125I seeds could make the tumor cell apoptosis rate increased, make Bcl-2 and VEGF expression level decreased, and make Bax expression increased, which were more obvious in 1.0 mCi group (P<0.05). The 125I seeds could increase the activity of caspase-3 within tumor tissue, but the difference between the 0.7 mCi group and the 1.0 mCi group was not significant (P>0.05). Conclusion The implanted 125I seeds can not only inhibit tumor’s growth through inducing apoptosis of tumor cells, but also inhibit tumor’s angiogenesis through influencing the expression of apoptosis-related gene and coding protein.

Objective:To solve the problems in intensity-modulated radiation therapy (IMRT) planning, such as large labor cost and high dependence on the experience of physicists and great inconsistency in the quality of plan, and to discuss an unsupervised automatic treatment planning procedure of IMRT.Methods:The eclipse scripting application programming interface (ESAPI) within the Eclipse treatment planning system (TPS) 15.6 and optimization parameters tree search algorithm (OPTSA) were used to emulate and realize the whole planning process. Interacted with the TPS through ESAPI, relevant dosimetric parameters were input and output. The OPTSA evaluated the plan qualities based on dosimetric parameters of the targets and organs at risk (OARs) and iteratively adjusted the optimization objective parameters to achieve a progressively improving IMRT plan. In order to verify the effectiveness of the automatic planning, twenty historical rectum cancer cases were selected from the clinical database, and the dose distribution and specific dosimetric parameters were compared between the plans generated by the OPTSA and the manual plans under the same constraints.Results:All the auto plans have met clinical requirements. Furthermore, 90% and 10% of the auto plans were deemed as clinically improved and equally compared with the manual plans, respectively. The average CI for the PTV was 0.88 and 0.80 for the auto and manual plans respectively. Compared with the manual plans, the mean doses of all the OARs in the auto plans were reduced by 11% in average. The average elapsed time of automatic planning and manual planning was (28.15±3.61) and (36.7±4.6) min, respectively.Conclusions:The plans created by the proposed algorithm have been shown to be at least as good as the manual plans. In addition, this method can shorten the labor time in plan designing while ensuring the plan quality and consistency of the plan.

Objective To analyze the clinical characteristics of patients with metastatic carcinoma of bone. Methods The clinical data of 217 patients with metastatic carcinoma of bone was retrospectively analyzed. The clinical features were summarized,including primary tumor,age distribution,first symptom,time of onset and bone metastatic site. Visual analogue scale(VAS)was used to evaluate the difference of pain in patients with bone metastases before and after zoledronic acid treatment. Results The bone metastasis occurred more frequently in men(male:female = 1.28:1). The majority of primary tumors were lung cancer(51.61％)and breast cancer (15.67％),respectively. The peak ages of the patients with metastatic carcinoma of bone were between 50 and 70 years old. Most of the patients with metastatic carcinoma of bone initially showed varying degrees of pain ,some of the patients with dysfunction,pathological fracture,or local lumps as the initial symptoms,only a tiny minority of patients were inadvertently found. Onset time was often within 3 months ,which accountings for 54.84％. Bone metastases were mostly in the spine,pelvis,femur and ribs,and most of the bone metastases were multiple. The VAS score of 108 patients who with bone metastases pain treated by zoledronic acid was 0～4(1.31 ± 1.07),with statistically significant differences compared with pretherapy(P<0.01). Conclusion In order to reduce the pain of patients,and to improve the quality of life and prolong the survival time,bone metastases should be diagnosed early and given comprehensive treatment.

Ischemic-type biliary lesion (ITBL) refers to biliary tract injury caused by insufficient blood supply of hepatic artery, which is one of the main factors affecting the long-term survival and quality of life of liver transplant recipients. The incidence of ITBL is associated with cold and warm ischemia, acute and chronic rejection, cytomegalovirus infection and the bile effect, etc. The occurrence of ITBL is a complicated process involving with multiple factors and steps. The therapeutic option of ITBL is extremely limited. A large proportion of ITBL patients should undergo repeated liver transplantation. ITBL has become one of the most critical factors preventing further advancement of liver transplantation. Hence, it is of significance to strengthen prevention and explore more effective modalities. Recent studies have found that toxic injury of bile salts plays a central role in ITBL. Active regulation of bile components, regulation of bile acid-related receptor expression and blockage or activation of bile acid-related signaling pathways probably have potentials in the prevention and treatment of ITBL. In this article, the cytotoxicity of bile salts and the mechanism of bicarbonate umbrella in the incidence and progression of ITBL after liver transplantation were reviewed, aiming to provide reference for the diagnosis and treatment of ITBL.

BACKGROUNDThe human FHIT gene at chromosome 3p14.2 is a tumor suppressor gene, and its abnormality in structure and function is related to carcinogenesis and progression of lung cancer. It is postulated that FHIT and NIT1 likewise collaborate in biochemical or cellular pathway in mammalian cells, but their molecular mechanisms in lung cancer cell are still unknown. The aim of this study is to construct procaryotic expression vector of human NIT1, providing a foundation to explore the expression of human NIT1 protein and to study the interaction of NIT1 and FHIT genes in lung cancer cell lines.

METHODSThe NIT1 cDNA was acquired by RT-PCR. EcoRI/NotI digested PCR product was directly cloned into procaryotic expression vector pET-32a.

RESULTSThe sequence of NIT1 cDNA clone exactly corresponded with the sequence of NIT1 cDNA in GenBank. The expectant fragments of DNA were obtained after recombinant procaryotic expression vector was digested by EcoRI and NotI.

CONCLUSIONSThe procaryotic expression vector of human NIT1 is successfully constructed by RT-PCR and direct clone. It provides an important basis to detect the expression of NIT1 protein and to further explore the relationship between NIT1 and FHIT genes in oncogenesis and development of human lung cancer.

Objective:To assess the three-dimensional dose distribution in radiotherapy plans using the structural similarity index(SSIM), compare the performance of SSIM with commonly used quality assessment indices, and develop a SSIM-based quality assessment method of multiple prescribed doses.Methods:The SSIM was introduced to providea quality score of various voxels by comparing actual and ideal three-dimensional dose data and combining the spatial location information of the voxels. Then the average value in a region of interest (ROI) was calculated as the quality score of the region. Fifty-three cases of cervical cancer were selected to analyze the correlation of the SSIM with the uniformity index (HI), conformity index (CI) of the dose distribution in various ROIs and to explore the capability of the SSIM to reflect the uniformity and conformity of dose distribution.Two types of quality defects were individually introduced into two of 53 radiotherapy plans. Then the two plans were compared with normal plans to characterize the response of the SSIM.Results:There was no correlation between HI and SSIM in positive lymph nodes(PGTVnd) due to the decrease in the HI sensitivity, while there was a significant negative correlation between them in regions where PGTVnd was removed from the planning target volume(PTV, R=-0.86, P<0.01). Meanwhile, there was a significant positive correlation between CI and SSIM in PGTVnd ( R=0.83, P<0.01). Therefore, the SSIM can be used to identify the artificial design defects in plans by determining abnormal dose gradients. Conclusions:Apart from reducing the defects of previous assessment parameters, the SSIM has the capability to assess the quality of radiotherapy plans by combining the uniformity and conformity of dose distribution and can provide accurate feedback on the spatial locations of quality defects.

Objective:To develope an automatic volumetric modulated arc therapy (VMAT) planning for rectal cancer based on a dose-prediction model for organs at risk(OARs) and an iterative optimization algorithm for objective parameter optimization.Methods:Totally 165 VMAT plans of rectal cancer patients treated in Peking University Cancer Hospital & Institute from June 2018 to January 2021 were selected to establish automatic VMAT planning. Among them, 145 cases were used for training the deep-learning model and 20 for evaluating the feasibility of the model by comparing the automatic planning with manual plans. The deep learning model was used to predict the essential dose-volume histogram (DVH) index as initial objective parameters(IOPs) and the iterative optimization algorithm can automatically modify the objective parameters according to the result of protocol-based automatic iterative optimization(PBAIO). With the predicted IOPs, the automatic planning model based on the iterative optimization algorithm was achieved using a program mable interface.Results:The IOPs of OARs of 20 cases were effectively predicted using the deep learning model, with no significantly statistical difference in the conformity index(CI) for planning target volume(PTV)and planning gross tumor volume(PGTV)between automatic and manual plans( P>0.05). The homogeneity index (HI) of PGTV in automatic and manual plans was 0.06 and 0.05, respectively( t=-6.92, P< 0.05). Compared with manual plans, the automatic plans significantly decreased the V30 for urinary bladder by 2.7% and decreased the V20 for femoral head sand auxiliary structure(avoidance)by 8.37% and 15.95%, respectively ( t=5.65, 11.24, P< 0.05). Meanwhile, the average doses to bladder, femoral heads, and avoidance decreased by 1.91, 4.01, and 3.88 Gy, respectively( t=9.29, 2.80, 10.23, P< 0.05) using the automatic plans. The time of automatic VMAT planning was (71.49±25.48)min in 20 cases. Conclusions:The proposed automatic planning based on dose prediction and an iterative optimization algorithm is feasible and has great potential for sparing OARs and improving the utilization rate of clinical resources.