Elevated expression of periostin in diabetic cardiomyopathy and the effect of valsartan.

BACKGROUND: Periostin, an extracellular matrix protein, plays a significant role in adverse cardiac remodeling. However, no report has documented the function of periostin in left ventricular remodeling of streptozototin (STZ)-induced diabetic rats. The aim of the present study was to observe the expression of periostin in Wistar rat's myocardium of diabetic cardiomyopathy (DCM) and the effect of valsartan on it. METHODS: Immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis were used to determine the degree of expression and location of periostin, transforming growth factor (TGF)-ß1, TGF-ß1 type II receptor (TGF-ß1 R II), and Type I and III collagens in the myocardium of STZ-induced diabetic rats. RESULTS: Periostin, TGF-ß1, TGF-ß1 R II, and Type I and III collagens were significantly increased in the myocardium of diabetic rats compared with control group on both messenger ribonucleic acid and protein levels. In addition, diabetic rats treated with valsartan could have reduced expression of periostin and improved cardiac remodeling of DCM. CONCLUSIONS: Periostin may play a crucial role in cardiac remodeling and myocardial interstitial fibrosis process of DCM and it could be one of the important mechanisms for valsartan to improve the ventricular remodeling of DCM.

[Study on origin and authentication of medicinal materials of Dalbergiae Lignum in crude drug's market].

The study is aimed to distinguish morphological characteristics of Dalbergiae Lignum collected from crude drug's markets and establish a identification methods and the quality standard for Dalbergiae Lignum. The macroscopic and microscopic features of Dalbergiae Lignum from crude drug's market were observed, analyzed and compared according to Hongmu specification issued by the People's Republic of China in 2000, and by the characteristics recorded in domestic monograph of Mucai Shibie (wood identification). The redwood of Dalbergiae Lignum cut into small pieces as medicinal material are dry heart wood of mahogany (trees from Dalbergia sp.), which characteristics of the small pieces as crude drug are different. There are differences in macroscopic and microscopic features about texture of wood and color, odor, taste, transverse section, radial section, tangential section. The results can provide basis for identification, application and improment of the quality standard of Dalbergiae Lignum as medicinal material.

Carbohydrate antigens as potential biomarkers for the malignancy in patients with idiopathic deep venous thrombosis: a retrospective cohort study.

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, ß2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (ß-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and ß2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and ß2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.

[Morphology study on traditional Chinese medicine of animal skeleton of osteon myospalacem baileyi].

Sailonggu, a traditional Chinese medicine is whole skeleton of Myospalax baileyi, which is a kind of animal of rodent from Qinghai-Tibet Plateau of China. Osteon Myospalacem Baileyiis the first category medicinal materials of China Food and Drug Administration. For better quality control, a method of the morphological identification of Osteon Myospalacem Baileyi was established by means of studying characteristics of the animal skeleton, it's microscopic characteristics of powder, and literatures comparison. The characteristics of Osteon Myospalacem Baileyi were observed and recorded in detail and marked by number, which could be used for identifying crude drug of Osteon Myospalacem Baileyi efficiently.

Synthesis and antiproliferative evaluation of new hybrids of piperine and acylhydrazone.

Piperine, a natural amide isolated from the genus of Piper, serves as a pharmacophore in medicinal chemistry. In this study, we synthesised and evaluated 18 novel piperine-acylhydrazone hybrids (4a-4r) for their antiproliferative activities in vitro. The structures of these hybrids were validated using 1H,13C NMR, and HR-ESI-MS data. Furthermore, we screened all synthesised compounds for their antiproliferative activities against three human cancer cell lines: FaDu (laryngeal carcinoma cells), HepG2 (hepatoblastoma carcinoma cells), and MGC803 (gastric carcinoma cells). Among them, compound 4o exhibited significantly inhibitory activities against FaDu, HepG2, and MGC803 with IC50 values of 13.85 ± 0.19, 11.02 ± 1.45, and 13.47 ± 3.43 µM, respectively, which was approximately two-fold lower than the positive control cisplatin. These findings suggest that compound 4o has the potential to be promising leads for the design of anti-cancer drugs.

Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study.

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, Liu WQ, Zhong CCW, Jiang MY, Mao C, Yang XB, Chung VCH, Wu IXY. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; 22(3): 223-234.

Effect of Trichinella spiralis infection on the immune response to HBV vaccine in a mouse model.

Vaccination is the most effective and cost-effective way to treat hepatitis B virus (HBV) infection. Collective data suggest that helminth infections affect immune responses to some vaccines. Therefore, it is important to reveal the effects of helminth infections on the efficacy of protective vaccines in countries with highly prevalent helminth infections. In the present work, effects of Trichinella spiralis infection on the protective efficacy of HBV vaccine in a mouse model were investigated. This study demonstrated that the enteric stage of T. spiralis infection could inhibit the proliferative response of spleen lymphocytes to hepatitis B surface antigen (HBsAg) and lead to lower levels of anti-HBsAg antibodies, interferon-γ, and interleukin (IL)-2, along with higher levels of IL-4 and IL-5. However, these immunological differences are absent in the muscle stage of T. spiralis infection. The results suggest that the muscle stage of T. spiralis infection does not affect the immune response to HBV vaccination, while the enteric-stage infection results in a reduced immune response to HBsAg.

[Advance of proteomic research on schistosome].

Schistosome proteome research may greatly enhance the understanding of immune mechanism, exploration of new diagnostic and vaccine candidates, and the development of new drugs. This article reviews the progress of proteomic research on schistosome from different life-cycle stages.

[Research on the effect of biyan qingdu granula drug-containing serum on inhibition of nasopharyngeal carcinoma cells growth in vitro].

OBJECTIVE: To investigate the effect of Biyan Qingdu Granula drug-containing serum (BQG-DS) on cell growth and apoptosis in nasopharyngeal carcinoma cell lines CNE1, CNE2, TWO3, C666-1, and explore the antineoplastic mechanism of Biyan Qingdu Granula. METHODS: SD rats were randomly divided into three groups: experimental (Biyan Qingdu Granula) group, positive control (cytoxan) group and negative control group. After administration of drug, the serum was collected from the treated animals. MTT assay was used to examine the effect of BQG-DS on the proliferation of CNE1, CNE2, TWO3, C666-1 cell, and flow cytometry was used to observe the cell cycle distribution. Apoptosis of CNE1, CNE2, TWO3, C666-1 cell was further investigated by inverted microscope. RESULTS: BQG-DS inhibited the proliferation of CNE1, CNE2, TWO3, C666-1 cell and the effects were in a time-and concentration-dependent manner. BQG-DS could also induce apoptosis while the G1 phase was arrested. CONCLUSION: BQG-DS inhibits proliferation of nasopharyngeal carcinoma cells via induction of apoptosis and arrest of cell cycle.

Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

BACKGROUND: Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. AIM: To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. METHODS: The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. RESULTS: The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. CONCLUSION: PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

RNF219 Promotes Nasopharyngeal Carcinoma Progression by Activating the NF-κB Pathway.

In Southeast Asia, the prevalence of nasopharyngeal carcinoma (NPC) is high; however, the molecular mechanism governing the progression of NPC is unclear. The results of the present study revealed upregulation of ring finger protein 219 (RNF219) expression in NPC tissues and cells. Overexpression of RNF219 enhanced NPC cell invasion, migration, and proliferation; whereas knockdown of RNF219 had the opposite effects. Mechanistically, RNF219 activated the nuclear factor kappa B (NF-κB) pathway, mainly reflected by increased p65 nuclear translocation, and increased NF-κB pathway target gene expression. NF-κB pathway inhibition in cells overexpressing RNF219 resulted in reduced invasion, migration, and proliferation, confirming that progression of NPC was promoted by RNF219-mediated NF-κB pathway activation. In addition, the expression of RNF219 correlated positively with the activity of the NF-κB pathway, verifying that RNF219 regulates the activity of the NF-κB pathway in the clinical setting. Our results identified a novel therapeutic target that could promote the development of novel treatments for NPC.

Body composition parameters were associated with response to abiraterone acetate and prognosis in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To investigate the predictive value of body composition parameters for biochemical response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients with prior chemohormonal therapy. METHODS: We retrospectively evaluated the clinicopathologic information of 132 mCRPC cases receiving AA treatment after chemohormonal therapy at hormone-sensitive stage from July 2018 to June 2021. All patients were divided into AA responders and non-responders according to the biochemical response to AA (prostate-specific antigen (PSA) reduction ≥50% than pretreatment). Multivariate Logistic analysis was used to determine the independent predictors and develop predictive model of biochemical response to AA. Cox regression analysis was utilized to investigate the prognostic factors for time to biochemical progression (TTBP), radiological progression-free survival (rPFS), failure-free survival (FFS), and overall survival (OS) after AA treatment. RESULTS: There were 57 AA responders and 75 AA non-responders. Periprostatic fat area/prostate area (PPFA/PA) was decreased and skeletal muscle index (SMI) was increased in AA responders compared with AA non-responders. Multivariable logistic analysis demonstrated that ADT duration ≥12 months, bone metastasis only, high SMI and low PPFA/PA were independent predictors of biochemical response to AA treatment. The FFS, TTBP, rPFS, and OS of patients with lower SMI or higher PPFA/PA was decreased compared with that of patients with higher SMI or lower PPFA/PA, respectively. Combining SMI, PPFA/PA, ADT duration and metastatic sites performed well in differentiating AA responders from non-responders. CONCLUSIONS: High SMI and low PPFA/PA could predict biochemical response to AA treatment and preferable prognosis in mCRPC patients with prior chemohormonal therapy at hormone-sensitive stage.

Delayed tail loss during the invasion of mouse skin by cercariae of Schistosoma japonicum.

A traditional assumption is that schistosome cercariae lose their tails at the onset of penetration. It has, however, recently been demonstrated that, for Schistosoma mansoni, cercarial tails were not invariably being shed as penetration took place and a high proportion of tails entered human skin under experimental conditions. This phenomenon was termed delayed tail loss (DTL). In this paper, we report that DTL also happens with S. japonicum cercariae during penetration of mouse skin. It occurred at all cercarial densities tested, from as few as 10 cercariae/2·25 cm(2) of mouse skin up to 200 cercariae. Furthermore, it was demonstrated that there was a density-dependent increase in DTL as cercarial densities increased. No such density-dependent enhancement was shown for percentage attachment over the same cercarial density range.

The effects of interleukin (IL)-12 and IL-4 deficiency on worm development and granuloma formation in Schistosoma japonicum-infected mice.

CD4(+) T-helper (Th) cell is widely recognized to be capable of influencing worm development and egg granuloma formation after schistosome infection. Interleukin (IL)-12 and IL-4 play key roles in regulation of Th cell differentiation. In the present study, we subcutaneously inoculated mice with hybridoma cells secreting monoclonal antibodies to neutralize IL-12 and IL-4 and explored the effects of IL-12 and IL-4 deficiency on the worm development and granuloma formation in mice infected with cercariae of Schistosoma japonicum. It was found that deficiency of host IL-12 and IL-4 supported normal parasite survival and fecundity. However, worm development (length and female fecundity) was significantly enhanced in anti-IL-12-treated mice. Mean length of worms in anti-IL-12-treated group was significantly greater than that of intact controls on day 28 after infection (females, 11.84 ± 1.20 mm vs. 9.45 ± 1.34; males, 9.35 ± 1.21 mm vs. 8.10 ± 0.85 mm, p < 0.05). Liver egg load per pair of worms (1,770.12 ± 470.67 vs. 806.08 ± 232.37, p < 0.05) and uterine egg load of ovigerous females (93.08 ± 27.85 vs. 46.05 ± 34.24, p < 0.05) in anti-IL-12-treated mice were significantly higher than those in intact control 28 days postinfection. But these effects diminished 42 days postinfection (p > 0.05). Granuloma size in anti-IL-12-treated mice was significantly larger than that in intact mice 42 days postinfection (398.3 ± 80.7 µm vs. 294.4 ± 72.2 µm, p < 0.05). Granuloma fibrosis dramatically intensified in anti-IL-12-treated mice but diminished in anti-IL-4-treated mice. The results suggest that IL-12 may play an impeditive role in the development of S. japonicum and in granuloma formation as well as fibrosis. IL-4 may promote granuloma formation but have no effect on worm development.

Cimetidine enhances the protective effect of GST DNA vaccine against Schistosoma japonicum.

Cimetidine (CIM), a histamine-2-receptor antagonist, has a long history of safe use in gastric acid-mediated gastrointestinal disorders. In this study, we used CIM, as an adjuvant, with pEGFP-Sj26 GST (the recombinant plasmid containing enhanced green fluorescent protein gene and the gene encoding 26 kDa glutathione S-transferase of Schistosoma japonicum) DNA vaccine to immunized mice and attempted to enhance the protective effect against S. japonicum. The results showed that the reduction rate of worm and egg burdens in the pEGFP-Sj26GST plus CIM group were 79.0% and 68.4%, respectively, significantly higher than that in pEGFP-Sj26GST alone group (27.0% and 22.5%, P<0.01). Compared with the pEGFP-Sj26GST alone group, mice immunized with pEGFP-Sj26GST plus CIM showed an elevated level of IFN-γ and IL-12 and a low level of IL-10 in splenocytes, while the levels of IL-4 and IL-5 showed no difference between the two groups. Our data also demonstrated that the percentage of CD4(+)CD25(+) regulatory T cells (Tregs) was significantly decreased in the spleens of mice immunized with pEGFP-Sj26GST plus CIM. All these findings suggest that CIM as a potential schistosome DNA vaccine adjuvant can enhance the protective effect of pEGFP-Sj26GST vaccine.

Effect of CD4+ CD25+ regulatory T cells on the immune evasion of Schistosoma japonicum.

It has been known that parasites developed sophisticated strategies to escape from the host immune assault. More recently, one strategy to induce immune evasion involved CD4(+)CD25(+) regulatory T cells (Tregs). Mice were infected with Schistosoma japonicum cercariae and then injected intraperitoneally with anti-CD25 monoclonal antibody (anti-CD25 mAb). The results showed that the percentages of CD4(+)CD25(+) Tregs in mice were expanded by S. japonicum infection, and it could be partially blocked by anti-CD25 mAb. Worm burden in anti-CD25 mAb group (23.17 ± 6.94) was significantly lower than that in infected group (30.17 ± 5.85). The level of interferon gamma was increased with anti-CD25 mAb administration; meanwhile, lower concentration of interleukin 10 was observed in the same group. These results suggest that CD4(+)CD25(+) Tregs contribute to the escape of S. japonicum from the host immune responses, while anti-CD25 mAb can partially block CD4(+)CD25(+) Tregs and enhance the protective immunity to the parasite by Th1-type immune response.

[Near infrared reflectance spectroscopy (NIRS): a novel approach to reconstructing historical changes of primary productivity in Antarctic lake].

Compared with traditional chemical analysis methods, reflectance spectroscopy has the advantages of speed, minimal or no sample preparation, non-destruction, and low cost. In order to explore the potential application of spectroscopy technology in the paleolimnological study on Antarctic lakes, we took a lake sediment core in Mochou Lake at Zhongshan Station of Antarctic, and analyzed the near infrared reflectance spectroscopy (NIRS) data in the sedimentary samples. The results showed that the factor loadings of principal component analysis (PCA) displayed very similar depth-profile change pattern with the S2 index, a reliable proxy for the change in historical lake primary productivity. The correlation analysis showed that the values of PCA factor loading and S2 were correlated significantly, suggesting that it is feasible to infer paleoproductivity changes recorded in Antarctic lakes using NIRS technology. Compared to the traditional method of the trough area between 650 and 700 nm, the authors found that the PCA statistical approach was more accurate for reconstructing the change in historical lake primary productivity. The results reported here demonstrate that reflectance spectroscopy can provide a rapid method for the reconstruction of lake palaeoenviro nmental change in the remote Antarctic regions.

[Ageing down-modulates the immune responses to Schistosoma japonicum infection in mice].

OBJECTIVE: To investigate the effect of ageing on the immune responses against Schistosoma japonicum infection in mice. METHODS: Female BALB/c mice were divided into young group (2 months) and old group (18 months), each composed of 8 mice. Each mouse was percutaneously infected with 40 +/- 1 S. japonicum cercariae. At 6 weeks post-infection, the mice were sacrificed, and the spleens were removed and single-cell suspensions of splenocytes were prepared. Worms were perfused from hepatic portal system and counted. The number of eggs in the liver was determined after KOH digestion. Mean single-egg granulomas sizes were determined in stained histological sections. Splenocyte proliferation responses were analyzed by MTT colorimetry. Level of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in the splenocyte culture supernatants was determined by ELISA. RESULTS: The worm burden and egg per gram of liver in old mice [19.75 +/- 1.95, (1.59 +/- 1.05) x 10(4)] were significantly lower than that of young mice [26.00 +/- 2.42, (208 +/- 0.87) x 10(4)] (P < 0.05). The mean volume of single-egg granulomas of the livers in old mice [(30.13 +/- 10.97) x 10(3) mm3] was significantly lower than that of the young mice [(47.02 +/- 24.13) x l0(3) mm3] (P < 0.05). RESULTS: of T cell proliferation showed that the splenocytes had poorer immune reactivity to ConA in old mice (SI: 1.08 +/- 0.12) than that in young mice (SI: 131 +/- 0.14) (P < 0.05). Levels of IFN-gamma and IL-4 in the splenocyte culture supernatants [(24.05 +/- 6.24), (4.15 +/- 0.68) pg/ml] from old mice were lower than that of young mice [(34.25 +/- 869), (7125 +/- 0.83) pg/ml](P < 0.05). CONCLUSION: Ageing down-modulates the immune responses and the poorer immune reactivity might decrease pathological alterations in mice infected with Schistosoma japonicum.

Half-Brain Delineation for Prediction of Radiation-Induced Temporal Lobe Injury in Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

PURPOSE: To investigate the role of half-brain delineation in the prediction of radiation-induced temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 220 NPC cases treated with IMRT and concurrent platinum-based chemotherapy were retrospectively analyzed. Dosimetric parameters of temporal lobes, half-brains, and brains included maximum dose (Dmax), doses covering certain volume (DV) from 0.03 to 20 cc and absolute volumes receiving specific dose (VD) from 40 to 80 Gy. Inter-structure variability was assessed by coefficients of variation (CV) and paired samples t-tests. Receiver operating characteristic curve (ROC) and Youden index were used for screening dosimetric parameters to predict TLI. Dose/volume response curve was calculated using the logistic dose/volume response model. RESULTS: CVs of brains, left/right half-brains, and left/right temporal lobes were 9.72%, 9.96%, 9.77%, 27.85%, and 28.34%, respectively. Each DV in temporal lobe was significantly smaller than that in half-brain (P < 0.001), and the reduction ranged from 3.10% to 45.98%. The area under the curve (AUC) of DV and VD showed an "increase-maximum-decline" behavior with a peak as the volume or dose increased. The maximal AUCs of DVs in brain, half-brain and temporal lobe were 0.808 (D2cc), 0.828 (D1.2cc) and 0.806 (D0.6cc), respectively, and the maximal AUCs of VDs were 0.818 (D75Gy), 0.834 (V72Gy) and 0.814 (V70Gy), respectively. The cutoffs of V70Gy (0.86 cc), V71Gy (0.72 cc), V72Gy (0.60 cc), and V73Gy (0.45 cc) in half-brain had better Youden index. TD5/5 and TD50/5 of D1.2cc were 58.7 and 80.0 Gy, respectively. The probability of TLI was higher than >13% when V72Gy>0 cc, and equal to 50% when V72Gy = 7.66 cc. CONCLUSION: Half-brain delineation is a convenient and stable method which could reduce contouring variation and could be used in NPC patients. D1.2cc and V72Gy of half-brain are feasible for TLI prediction model. The dose below 70 Gy may be relatively safe for half-brain. The cutoff points of V70-73Gy could be considered when the high dose is inevitable.

Potential Defects and Improvements of Equivalent Uniform Dose Prediction Model Based on the Analysis of Radiation-Induced Brain Injury.

PURPOSE: To study the impact of dose distribution on volume-effect parameter and predictive ability of equivalent uniform dose (EUD) model, and to explore the improvements. METHODS AND MATERIALS: The brains of 103 nasopharyngeal carcinoma patients treated with IMRT were segmented according to dose distribution (brain and left/right half-brain for similar distributions but different sizes; V D with different D for different distributions). Predictive ability of EUDV D (EUD of V D ) for radiation-induced brain injury was assessed by receiver operating characteristics curve (ROC) and area under the curve (AUC). The optimal volume-effect parameter a of EUD was selected when AUC was maximal (mAUC). Correlations between mAUC, a and D were analyzed by Pearson correlation analysis. Both mAUC and a in brain and half-brain were compared by using paired samples t-tests. The optimal D V and V D points were selected for a simple comparison. RESULTS: The mAUC of brain/half-brain EUD was 0.819/0.821 and the optimal a value was 21.5/22. When D increased, mAUC of EUDV D increased, while a decreased. The mAUC reached the maximum value when D was 50-55 Gy, and a was always 1 when D ≥55 Gy. The difference of mAUC/a between brain and half-brain was not significant. If a was in range of 1 to 22, AUC of brain/half-brain EUDV55 Gy (0.857-0.830/0.845-0.830) was always larger than that of brain/half-brain EUD (0.681-0.819/0.691-0.821). The AUCs of optimal dose/volume points were 0.801 (brain D2.5 cc), 0.823 (brain V70 Gy), 0.818 (half-brain D1 cc), and 0.827 (half-brain V69 Gy), respectively. Mean dose (equal to EUDV D with a = 1) of high-dose volume (V50 Gy-V60 Gy) was superior to traditional EUD and dose/volume points. CONCLUSION: Volume-effect parameter of EUD is variable and related to dose distribution. EUD with large low-dose volume may not be better than simple dose/volume points. Critical-dose-volume EUD could improve the predictive ability and has an invariant volume-effect parameter. Mean dose may be the case in which critical-dose-volume EUD has the best predictive ability.