1.Analysis of the evolution of esophageal tumor volume in radiotherapy process using a mathematical model.
Baohui LIANG ; Wanxin WEN ; Wei ZHAN ; Xujing LU ; Zhenlong JIANG
Journal of Biomedical Engineering 2013;30(4):752-755
The volume change of tumor during radiotherapy processes indirectly reflects the short-term efficacy and the quality of radiotherapy planning. We analyzed clinical data of radiotherapy using a mathematical model in our study. First, we selected eight esophageal carcinoma patients with only using 3DRT and conventional dose fractionation schemes. And then we observed and measured the change of tumor volume during the radiotherapy. Based on the LQ model, repopulation and re-oxygenation in 4Rs, and the kinetics of doomed tumor disintegration, we established the mathematical model of tumor evolution in radiotherapy. And then we used the model to analyze the clinical trial data about esophageal carcinoma with radiotherapy. It was proved that the results of the model almost coincided with the clinical trial data. According to the analysis results, we could get the related radiobiology parameters to estimate biological effective dose and repopulation of patients. The mathematical model could provide reference for assessment of prognosis and further scheme of treatment.
Algorithms
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Esophageal Neoplasms
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pathology
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radiotherapy
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Humans
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Models, Theoretical
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Radiotherapy Planning, Computer-Assisted
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methods
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Tumor Burden
2.Mathematical model of tumor evolution in radiotherapy.
Baohui LIANG ; Wanxin WEN ; Baizhen WANG ; Mingna CAO ; Wei ZHAN
Journal of Biomedical Engineering 2012;29(6):1094-1097
The schemes of dose fractionation play an important role in tumor radiotherapy. We used mathematical methods to describe the process of tumor cells evolution during radiotherapy, trying to find how the schemes of dose fractionation affect tumor cells. In clinical radiobiology, linear-quadratic (LQ) model is frequently used to describe radiation effects of tumor cells. We integrated LQ model with effect of oxygen, and with the phenomenon of repopulation and reoxygenation in the theory of radiation biology. While we considered the disappearing progress of doomed cells in tumor, we established the mathematical model of tumor evolution in radiotherapy. We simulated some common treatment schedules, and studied the change role of tumor cells during radiotherapy. These results can serve for the optimization of dose fractionation scheme based on tumor radiobiological characteristics.
Cell Growth Processes
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radiation effects
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Dose Fractionation
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Humans
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Models, Theoretical
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Neoplasms
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pathology
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physiopathology
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radiotherapy
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Radiobiology
3.Synthesis and biodistribution of a bi-functional agent 99Tcm-Gd-DTPA-DG in tumor bearing nude mice
Wei, ZHANG ; Liang, CAI ; Yue, CHEN ; Zhan-wen, HUANG ; Zhi-ling, DING ; Feng, CAO ; Li, ZHANG ; Ling, HE
Chinese Journal of Nuclear Medicine 2011;31(2):117-120
Objective To evaluate the stability and biodistribution of a novel SPECT-MRI bi-functional agem 99Tcm-Gd-DTPA-DG in tumor-bearing nude mice. Methods DTPA-DG was synthesized and then conjugated with Gd2O3 to generate Gd-DTPA-DG. The tumor-bearing nude mice were scanned by MRI to evaluate the tumor targeting ability of Gd-DTPA-DG. The orthogonal experiment was applied to optimize pH value of reaction medium and reaction temperature. The radiolabeling efficiency was measured by thin layer chromatography. The distribution of 99Tcm-Gd-DTPA-DG in nude mice was evaluated by scintigrapy in vivo. The % ID/g was measured at different time after intravenous injection of 99Tcm-Gd-DTPA-DG. Results The tumor was significantly enhanced by Gd-DTPA-DG with MRI. The radiochemical purity of 99Tcm-Gd-DTPADG was about 98.5% and remained 96.2% at room temperature for 6 h. The tumor was well visualized by 99TcmGd-DTPA-DG SPECT at 2 h after injection. The tumor uptake was (1.48 ±0.12) %ID/g, and the rumor to muscle radioactivity ratio was 2.91. Conclusions MRI contrast of Gd-DTPA-DG may enhance tumor detection. 99Tcm-labeled Gd-DTPA-DG may be useful for tumor imaging and might have a potential role as a SPECT-MRI bi-functional agent.
4.Efficacy of large decompressive craniectomy in severe traumatic brain injury.
Gu LI ; Liang WEN ; Xiao-feng YANG ; Xiu-jue ZHENG ; Ren-ya ZHAN ; Wei-guo LIU
Chinese Journal of Traumatology 2008;11(4):253-256
OBJECTIVETo investigate the role of large decompressive craniectomy (LDC) in the management of severe and very severe traumatic brain injury (TBI) and compare it with routine decompressive craniectomy (RDC).
METHODSThe clinical data of 263 patients with severe TBI (GCS < or = 8) treated by either LDC or RDC in our department were studied retrospectively in this article. One hundred and thirty-five patients with severe TBI, including 54 patients with very severe TBI (GCS < or = 5), underwent LDC (LDC group). The other 128 patients with severe TBI, including 49 patients with very severe TBI, underwent RDC (RDC group). The treatment outcome and postoperative complications of the two treatment methods were compared and analyzed in a 6-month follow-up period.
RESULTSNinety-six patients (71.7 %) obtained satisfactory treatment outcome in the LDC group, while only 75 cases (58.6 %) obtained satisfactory outcome in the RDC group (P < 0.05). Moreover, the efficacy of LDC in treating very severe TBI was higher than that of RDC (63.0 % vs. 36.7 %, P < 0.01). The chance of reoperation due to refractory intracranial pressure (ICP) in the LDC group was significantly lower than that of the RDC group (P < 0.05), while the incidences of delayed intracranial hematoma and subdural effusion were significantly higher than those of the RDC group ( P < 0.05).
CONCLUSIONSLDC is superior to RDC in improving the treatment outcome of severe TBI, especially the very severe ones. LDC can also efficiently reduce the chances of reoperation due to refractory ICP. However, it increases the incidences of delayed intracranial hematoma and contralateral subdural effusion.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain Injuries ; surgery ; Child ; Child, Preschool ; Craniotomy ; adverse effects ; Decompression, Surgical ; adverse effects ; Female ; Humans ; Infant ; Intracranial Pressure ; Male ; Middle Aged
5.Growth inhibition of combined pathway inhibitors on KRAS mutated non-small cell lung cancer cell line.
Zhan-wen LI ; Zhen-li YANG ; Hai-liang FENG ; Xiao-cui BIAN ; Yan-yan LIU ; Yu-qin LIU
Chinese Journal of Pathology 2013;42(5):330-335
OBJECTIVETo investigate the effect of the selective PI3K inhibitor and MEK inhibitor on KRAS and PTEN co-mutated non-small cell lung cancer cell line NCI-H157 and the relevant mechanisms.
METHODSNCI-H157 was cultured routinely and treated with different concentrations of the two inhibitors. Cell proliferation was detected by MTT cell cycle assay. Based on the MTT results the cells were divided into four groups: the control group, PI3K inhibitor group (GDC-0941, 0.5 and 5.0 µmol/L), combination group I (0.5 µmol/L AZD6244 + 0.5 µmol/L GDC-0941) and combination group II (5.0 µmol/L AZD6244 + 5.0 µmol/L GDC-0941). Colony formation assay was performed to detect colony formation efficiency. The cell cycle and apoptosis were analyzed by flow cytometry. The expression of protein related to apoptosis was tested with Western blot.
RESULTSCell growth was inhibited by the two inhibitors. Combination groups led to stronger cell proliferation inhibition: combination group Ishowed synergistic effect of their actions and combination group II showed an additive effect; in both groups, there were decreased colony number [(77.2 ± 1.54)/well vs (61.50 ± 2.12)/well, P < 0.01] and [(51.00 ± 4.00)/ well vs (22.50 ± 3.53)/well, P < 0.01]; and enhanced apoptotic ratios [(18.30 ± 0.82)% vs (21.32 ± 0.56)%, P < 0.01] and [(27.14 ± 1.58)% vs (42.45 ± 4.42)%, P < 0.01]. In addition, compared to the PI3K inhibitor alone group, the NCI-H157 cells in the combination groups showed increased G0/G1 phase and decreased S phase (P < 0.01). Western blotting showed that the combination groups demonstrated significantly decreased expression of cyclin D1 and cyclin B1, increased p21 and cleaved PARP and decreased bcl-2/bax ratio, compared to the PI3K inhibitor only group.
CONCLUSIONThe combined inhibition of PI3K (AZD6244) and MEK (GDC-0941) has synergistic effects on the proliferation of NCI-H157 cells, but such effects appear to be in a dose-dependent manner.
Apoptosis ; drug effects ; Benzimidazoles ; administration & dosage ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin B1 ; metabolism ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Indazoles ; administration & dosage ; pharmacology ; Lung Neoplasms ; genetics ; pathology ; Mitogen-Activated Protein Kinase Kinases ; antagonists & inhibitors ; metabolism ; Mutation ; PTEN Phosphohydrolase ; genetics ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Poly(ADP-ribose) Polymerases ; metabolism ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Proto-Oncogene Proteins p21(ras) ; metabolism ; Signal Transduction ; Sulfonamides ; administration & dosage ; pharmacology ; bcl-2-Associated X Protein ; metabolism ; ras Proteins ; genetics
6.Bridging fixation with locking plate for the treatment of subtrochanteric femoral fractures of Seinsheimer type V.
Yin-wen LIU ; Yu-xin ZHENG ; Zi-liang SHEN ; Shu-qiang WANG ; Xiao-en WEI ; Lei ZHANG ; Xin-feng GU ; Yong KUANG ; Hong-sheng ZHAN ; Yin-yu SHI
China Journal of Orthopaedics and Traumatology 2016;29(1):68-72
OBJECTIVETo investigate the clinical effect of bridging fixation with locking plate for the Seinsheimer type V subtrochanteric femoral fracture.
METHODSFrom March 2009 to September 2014,18 cases of Seinsheimer type V subtrochanteric femoral fracture were treated by open reduction and bridging fixation with locking plate through proximal and distal approach including 16 males and 2 females with an average age of 41 years old ranging from 22 to 67 years old. Among them, 12 cases caused by traffic accident, 5 cases by falling, 1 case by heavy aboving. All cases were fresh and closed fractures. Time between injury and operation was from 4 to 9 days with an average of 6.2 days. Of them, 11 cases were fixed with reverse LISS and the other 7 cases were fixed with anatomical locking plates of proximal femur.
RESULTSThe mean time of operation was 110 min (ranged from 90 to 155 min). The mean blood loss during operation was 425 ml (ranged from 350 to 650 ml) and 16 cases got blood transfusion which was meanly 300 ml. The mean hospital time was 14 days (ranged from 12 to 18 days). The mean duration of followed up was 11.8 months (ranged from 8 to 22 months). The mean time of bone union was 6.6 months (ranged from 5 to 8 months). There was not any complication such as infection, implant failure, hip varus, external rotation deformity of low limb or fat embolism. The Sanders hip scores were 53.22 ± 6.48, the result was excellent in 12 cases and good in 6 cases at the last follow-up.
CONCLUSIONUnder the principle of biological osteosynthesis, treatment of Seinsheimer type V subtrochanteric femoral fracture with bridging locking plate fixation has such advantages as high mechanism, less interference of blood supply, stable fixation and little complication. It is a safe and idea way for the treatment of the Seinsheimer type V subtrochanteric femoral fracture.
Adult ; Aged ; Bone Plates ; Female ; Fracture Fixation, Internal ; methods ; Hip Fractures ; surgery ; Humans ; Male ; Middle Aged
7.Ultra-Early Surgery for Poor-Grade Intracranial Aneurysmal Subarachnoid Hemorrhage: A Preliminary Study.
Jian Wei PAN ; Ren Ya ZHAN ; Liang WEN ; Ying TONG ; Shu WAN ; Yong Ying ZHOU
Yonsei Medical Journal 2009;50(4):521-524
PURPOSE: To describe the therapeutic effect and possibility of the ultra-early surgery for poor-grade aneurysmal subarachnoid hemorrhage (Hunt-Hess grades IV - V). MATERIALS AND METHODS: Nine cases with intracranial aneurysms, demonstrated by computed tomographic angiography (CTA), were treated by ultra-early surgery under general anesthesia within 24 hours from subarachnoid hemorrhage (SAH), 5 cases were treated within 6 hours and 4 cases in 6 - 24 hours. Preoperative Hunt-Hess grade: 6 cases were IV and 3 cases were V. The clinical outcome was evaluated by Glasgow Outcome Scores (GOS). RESULTS: In operation, difficult dissection occurred in 5 cases (55.6%), and rupture of aneurysm occurred and temporary obstructions were performed in 4 cases (44.4%). After clipping of aneurysm, 2 cases underwent V-P shunt because of hydrocephalus, pulmonary infection occurred in 3 cases, hypothalamus reaction accompanied with upper gastrointestinal hemorrhage in 2 cases. The clinical outcome were favorable (GOS 4 - 5) in 4 cases (44.4%), dissatisfied (GOS 2 - 3) in 3 cases (33.3%), and dead (GOS 1) in 2 cases (22.2%) when patients departed from our hospital. CONCLUSION: The ultra-early surgery can avoid early rebleeding of intracranial aneurysm, therefore, should be considered in the treatment of Hunt-Hess grade IV-V intracranial aneurysms. The appliance of CTA can make it possible to use of ultra-early surgery and improve the therapeutic effect.
Adult
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Aged
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Cerebral Angiography
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Female
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Humans
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Intracranial Aneurysm/pathology/*surgery
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Male
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Middle Aged
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Subarachnoid Hemorrhage/pathology/*surgery
8.A case report of giant cemento-ossifying fibroma.
Run lU ; Wen-wu LIANG ; Zhan YANG ; Chun-hai LIU ; Yue-tao ZHAO
West China Journal of Stomatology 2010;28(6):682-683
Cemento-ossifying fibroma is a rare benign tumor from periodontium, which usually occurs in mandible body and mandible ramus. It consists of collagen fibrils, fibroblast, and cementoblast. This article reported a case of giant cemento-ossifying fibroma and discussed the clinical features and treatment.
Dental Cementum
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Fibroblasts
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Fibroma, Ossifying
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Humans
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Mandible
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Periodontal Ligament
9.Effects of extracts of pericarpium citri reticulatae and pogostemon cablin on the contraction of gastrointestinal smooth muscle and gastrointestinal hormones in rats with gastrointestinal motility disorder
kun Zhan HE ; liang Guo ZHANG ; Fang TANG ; chao Jin DU ; jie Wen JIN
Tianjin Medical Journal 2017;45(11):1175-1179
Objective To investigate the effects of different extracts of pericarpium citri reticulatae (PCR) and pogostemon cablin benth (PCB) on the contraction of gastrointestinal smooth muscle and the level of gastrointestinal hormones in rat model of gastrointestinal motility disorder. Methods Seventy Wistar rats were randomly divided into groups of control, model, water extractive of PCR, hesperidin, water extractive of PCB, water extractive of PCB plus volatile oil and patchouli alcohol, ten rats in each group. Except the control group, the rest groups were established gastrointestinal motor disorder model via limb ischemia-reperfusion (LIR). After modeling rats of groups were intervened with corresponding extracts. The effects of different extracts on contraction amplitude of corpora ventriculi and small intestine smooth muscle were observed. The levels of gastrointestinal hormones including motilin (MOT), gastrin (GAS), cholecystokinin (CCK) and somatostatin (SS) were detected by radioimmunoassay. Results The contraction amplitudes of corpora ventriculi and small intestine smooth muscle were decreased (P<0.05), the serum level of GAS and plasma level of MOT were also significantly decreased, while CCK and SS levels in the gastric antrum were significantly increased in model group than those of the control group (P < 0.05). Water extractive of PCR, hesperidin, water extractive of PCB and water extractive of PCB +patchouli oil can increase the contraction amplitudes of corpora ventriculi and small intestine smooth muscle, increase the serum level of GAS and reduce levels of CCK and SS in the gastric antrum (P<0.05), whereas showed no influence in the plasma level of MOT (P>0.05)]. Compared with model group, patchouli alcohol showed no influence in the contraction of gastrointestinal smooth muscle and levels of MOT, GAS, CCK and SS (P>0.05). In the aspect of regulating the contraction of gastrointestinal smooth muscle and the level of GAS, CCK and SS, the pharmacological effect of PCR water extract was better than that of hesperidin (P<0.05), while water extractive of PCB+volatile oil was better than that of water extractive of PCB (P < 0.05). Conclusion The active ingredients of PCR and PCB have variant regulative effects on the contraction of gastrointestinal smooth muscle and the serum level of GAS, CCK and SS in the gastric antrum in rat model of gastrointestinal motility disorder.
10.Exploring the mechanism of regulating Bcl-2/Bax pathway by the therapy of promoting blood circulation and nourishing yin to improve spermatogenesis in rats with varicocele
Yichun LIANG ; Wen WANG ; Shulin LIANG ; Ruijie FU ; Zhan QIN ; Liguo GENG ; Chaoba HE ; Shaoying YUAN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1481-1489
Objective To explore the mechanism of the therapy of promoting blood circulation and nourishing yin(PBCNY)in improving spermatogenesis in rats with varicocele based on Bcl-2/Bax pathway.Methods Thirty 8-week-old male SD rats were randomly divided into six groups(five rats per group):sham,model,levocarnitine(1.0 g/kg),and PBCNY low-dose(5.2 g/kg),PBCNY medium-dose(10.4 g/kg),and PBCNY high-dose(20.8 g/kg)groups.Apart from the sham group,all the groups were built a varicocele model by the classical Turner method.After 4 weeks,the sham group and model group were gavaged with normal saline,and the remaining groups were given with levocarnitine or different doses of PBCNY decoction once a day for 4 weeks.At the end of gavage,the sperm quality of rats in each group was detected by a computer-assisted sperm analyzer,and HE staining was used to observe the testicular tissue morphology of rats in each group and performed with Johnsen score.TUNEL method was used to detect apoptosis,RT-qPCR was used to detect Bcl-2 and Bax mRNA expression,and immunohistochemical method was used to detect cytochrome C protein expression.Results Compared to the sham group,sperm total count,motility rate and percentage of sperm with grade(a+b)motility were lower in the model group of rats(P<0.05).HE staining showed disturbed arrangement of seminiferous tubules in the testicular tissue with significant changes and decreased Johnsen score(P<0.05).The result of TUNEL assay showed that the apoptosis rate was increased in the model group(P<0.05).Bax mRNA expression was increased in testicular tissue(P<0.05).The result of immunohistochemistry showed that the positive expression of cytochrome C was increased in the model group(P<0.05).Compared with the model group,the rat sperm total count in the PBCNY medium-dose group,motility rate in the PBCNY low-and medium-dose groups,and percentage of sperm with grade(a+b)motility in the PBCNY low-dose group increased(P<0.05);the pathological structure of rat testis had different degrees of improvement,and Johnsen score increased in the PBCNY medium-dose group(P<0.05);the apoptosis rate of testicular cells decreased in the levocarnitine group and all doses of PBCNY groups(P<0.05);the expression of Bcl-2 mRNA increased in the PBCNY low-dose and high-dose groups(P<0.05),and the expression of Bax mRNA decreased in the levocarnitine group and the PBCNY medium-dose group(P<0.05);the positive expression of cytochrome C decreased in the PBCNY medium-dose group(P<0.05).Conclusion The therapy of PBCNY can improve sperm quality,repair damaged testicular tissue structure and improve spermatogenic function in rats with varicocele,and its mechanism of action may be related to the activation of Bcl-2/Bax pathway and inhibition of cell apoptosis.