Radiomics and dosiomics for predicting radiation-induced hypothyroidism and guiding intensity-modulated radiotherapy.

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

Dosimetric impact of CT metal artifact reduction for spinal implants in stereotactic body radiotherapy planning.

Background: Metal artifacts due to spinal implants may affect the accuracy of dose calculation for radiotherapy. However, the dosimetric impact of metal artifact reduction (MAR) for spinal implants in stereotactic body radiotherapy (SBRT) plans has not been well studied. The objective of this study was to evaluate the dosimetric impact of MAR in spinal SBRT planning with three clinically common dose calculation algorithms. Methods: Gammex phantom and 10 patients' computed tomography (CT) images were studied to investigate the effects of titanium implants. A commercial orthopedic MAR algorithm was employed to reduce artifacts. Dose calculations for SBRT were conducted on both artifact-corrected and uncorrected images using three commercial algorithms [analytical anisotropic algorithm (AAA), Acuros XB (AXB), and Monte Carlo (MC)]. Dose discrepancies between artifact-corrected and uncorrected cases were appraised using a dose-volume histogram (DVH) and 3-dimensional (3D) gamma analysis with different distance to agreement (DTA) and dose difference criteria. The gamma agreement index (GAI) was denoted as G(∆D, DTA). Statistical analysis of t-test was utilized to evaluate the dose differences of different algorithms. Results: The phantom study demonstrated that titanium metal artifacts can be effectively reduced. The patient cases study showed that dose differences between the artifact-corrected and uncorrected datasets were small evaluated by gamma index and DVH. Gamma analysis found that even the strict criterion local G(1,1) had average values ≥93.9% for the three algorithms. For all DVH metrics, average differences did not exceed 0.7% in planning target volume (PTV) and 2.1% in planning risk volume of spinal cord (PRV-SC). Statistical analysis showed that the observed dose differences of MC method were significantly larger than those of AAA (P<0.01 for D98% of PTV and P<0.001 for D0.1cc of spinal cord) and AXB methods (P<0.001 for D98% and P<0.0001 for D0.1cc). Conclusions: Dosimetric impact of artifacts caused by titanium implants is not significant in spinal SBRT planning, which indicates that dose calculation algorithms might not be very sensitive to CT number variation caused by titanium inserts.

Immunochemotherapy alone or immunochemotherapy plus subsequent locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma.

BACKGROUND: To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy. MATERIALS AND METHODS: A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation. RESULTS: There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities. CONCLUSION: Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management.

Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal carcinoma.

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

Dosiomics Risk Model for Predicting Radiation Induced Temporal Lobe Injury and Guiding Individual Intensity-Modulated Radiation Therapy.

PURPOSE: We aimed to assess the value of dose distribution-based dosiomics and planning computed tomography-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity modulated radiation therapy. METHODS AND MATERIALS: A total of 5599 nasopharyngeal carcinoma patients were enrolled, including 2503, 1072, 988, and 1036 patients in the training, validation, prospective test, and external test cohorts, respectively. The concordance index (C-index) was used to compare the performance of the radiomics and dosiomics models with that of the quantitative analyses of normal tissue effects in the clinic and Wen's models. The predicted TLI-free survival rates of redesigned simulated plans with the same dose-volume histogram but different dose distributions for same patient in a cohort of 30 randomly selected patients were compared by the Wilcoxon matched-pairs signed-rank test. RESULTS: The radiomics and dosiomics signatures were constructed based on 30 selected computed tomography features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P <.001). However, the radiomics signature had a low C-index. The dosiomics risk model combining the dosiomics signature, D1cc, and age had favorable performance, with C-index values of 0.776, 0.811, 0.805, and 0.794 in the training, validation, prospective test, and external test cohorts, respectively, which were better than those of the quantitative analyses of normal tissue effects in the clinic model and Wen's model (all P <.001). The dosiomics risk model can further distinguish patients in a same risk category divided by other models (all P <.05). Conversely, the other models were unable to separate populations classified by the dosiomics risk model (all P > .05). Two simulated plans with the same dose-volume histogram but different dose distributions had different TLI-free survival rates predicted by dosiomics risk model (all P ≤ .002). CONCLUSIONS: The dosiomics risk model was superior to traditional models in predicting the risk of TLI. This is a promising approach to precisely predict radiation-induced toxicities and guide individualized intensity modulated radiation therapy.

Benefit of [18F] FDG PET/CT in the diagnosis and salvage treatment of recurrent nasopharyngeal carcinoma.

PURPOSE: To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS). METHODS: Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression. RESULTS: PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005). CONCLUSION: PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS.

Analysis of Treatment Outcomes and Prognosis After Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer.

The aims of this study were to investigate the short-term and long-term efficacies and chronic radiotoxicity of concurrent chemoradiotherapy (CCRT) combined with image-guided adaptive brachytherapy (IGABT) in patients with locally advanced cervical cancer (LACC) and identify prognostic factors in this patient population. The clinical data of 204 patients with cervical cancer who completed CCRT and subsequent brachytherapy in our hospital between February 2015 and March 2017 were retrospectively analyzed. Short-term and long-term outcomes, chronic radiotoxicity, and prognostic factors were assessed. The median follow-up was 61.1 months. The short-term objective response (OR) rate was 85%. Lymph node metastasis before treatment was an independent predictor of OR (HR = 6.290, 95% CI: 2.211-17.897, p = 0.001). Fifty-two patients developed recurrence, with a median recurrence-free survival of 9.9 months (range, 2.4-52.2 months) and a post-recurrence survival of 12.1 months (range, 2.9-58.1 months). At 3 years, the cumulative incidence of overall recurrence was 26% (95% CI: 17-36). Multivariate analysis showed that Stage IIIB (HR = 2.332, 95% CI: 1.195-4.551, p = 0.013; reference, Stage IIB) and lymph node metastasis (HR = 4.462, 95% CI: 2.365-8.419, p < 0.001) were significant independent predictors of recurrence. Fifty-three patients developed chronic radiation proctitis (CRP). The incidence of severe CRP was approximately 5%, and the average rectal D 2 c m 3 accumulation in patients with severe CRP was 73.4 Gy which is 3.9 Gy higher than that in patients without CRP (p = 0.013). At 4 years, the overall survival (OS) and disease-free survival rates were 65% and 62%, respectively, and lymph node metastasis before treatment was an independent prognostic risk factor for OS. The short-term and long-term efficacies of CCRT combined with IGABT for the treatment of LACC patients were relatively satisfactory. However, the short-term and long-term efficacies of patients with lymph node metastasis before treatment were poor. For patients with lymph node metastasis before treatment, more active individualized treatment strategies should be adopted. When designing a radiotherapy plan, it is necessary to strictly limit the rectal D 2 c m 3 accumulation to prevent serious CRP.

Comparison of combinations of irradiation techniques and jaw conditions in intensity-modulated radiotherapy for lung cancer.

PURPOSE: To assist in the selection of a suitable combination of an irradiation technique and jaw condition in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) for lung cancer treatment plans. MATERIALS AND METHODS: Thirty patients with lung cancer who underwent radiotherapy were enrolled retrospectively. They were categorized as having central lung cancer, peripheral lung cancer with mediastinal lymph node metastasis (peripheral E lung cancer), and peripheral lung cancer without mediastinal lymph node metastasis (peripheral N lung cancer). Four treatment plans were designed for each patient: fixed jaw and adaptive jaw IMRT technique (FJ-IMRT and JA-IMRT), and fixed jaw and jaw tracking VMAT technique (FJ-VMAT and JT-VMAT). The dose parameters of the four group plans were compared and analyzed. RESULTS: Compared to FJ-IMRT, JA-IMRT significantly reduced the mean dose (Dmean ) and volume percentage of 5 Gy (V5Gy ) of the total lung in central and peripheral N lung cancer. Similarly, compared to FJ-VMAT, JT-VMAT provided better protection to most organs at risk (OARs), particularly for total lung and heart. In comparison with IMRT, VMAT significantly improved the conformity index (CI) of the planning target volume for the three lung cancer classifications, and it reduced the dose of almost all OARs except V5Gy and Dmean of the total lung. Moreover, the mean monitor units of the VMAT groups were far lower than the IMRT groups. CONCLUSION: Based on the dosimetric findings and considering clinical data published on lung and heart side effects, we propose recommendations on the preferred treatment technique based on tumor location and pulmonary function. For central lung cancer with normal pulmonary function, we advise JT-VMAT techniques. Conversely, for central lung cancer with poor pulmonary function, we recommend JA-IMRT techniques. We advocate JA-IMRT for peripheral E lung cancer. For peripheral N lung cancer, JT-VMAT techniques are strongly recommended.

[Accuracy of different image registration methods in image-guided adaptive brachytherapy for cervical cancer].

OBJECTIVE: To compare the accuracy of different methods for image registration in image-guided adaptive brachytherapy (IGABT) for cervical cancer. METHODS: The last treatment planning CT images (CT1) and the first treatment planning CT images (CT2) were acquired from 15 patients with cervical cancer and registered with different match image qualities (retained/removed catheter source in images) and different match regions [target only (S Group)/ interested organ structure (M Group)/body (L Group)] in Velocity3.2 software. The dice similarity coefficient (DSC) between the clinical target volumes (CTV) of the CT1 and CT2 images (CTVCT1 and CTVCT2, respectively) and between the organs-at-risk (OAR) of the two imaging datasets (OARCT1 and OARCT2, respectively) were used to evaluate the image registration accuracy. RESULTS: The auto-segmentation volume of the catheter source using Velocity software based on the CT threshold was the closest to the actual volume within the CT value range of 1700-1800 HU. In the retained group, the DSC for the OARs of was better than or equal to that of the removed group, and the DSC value of the rectum was significantly improved (P < 0.05). For comparison of different match regions, the high-risk target volume (HRCTV) and the low-risk target volume (IRCTV) had the best precision for registration of the target area, which was significantly greater than that of M group and L group (P < 0.05). The M group had better registration accuracy of the target area and the best accuracy for the OARs. The DSC values of the bladder and rectum were significantly better than those of the other two groups (P < 0.05). CONCLUSIONS: The CT value range of 1700-1800 HU is optimal for automatic image segmentation using Velocity software. Automatic segmentation and shielding the volume of the catheter source can improve the image quality. We recommend the use of interested organ structures regions for image registration in image-guided adaptive brachytherapy for cervical cancer.

Prognostic value of serum bilirubin in southern Chinese patients with advanced nasopharyngeal carcinoma.

BACKGROUND: We evaluated the prognostic value of serum bilirubin in advanced nasopharyngeal carcinoma (NPC) patients. METHODS: Seven-hundred fifty-nine advanced NPC patients treated with definitive chemoradiotherapy were retrospectively analyzed. Serum indirect bilirubin (IBIL) and direct bilirubin (DBIL) were measured before treatment. To evaluate different cutoff points for serum bilirubin, we utilized ROC curves. The Kaplan-Meier method and log-rank test were adopted to calculate and compare survival outcomes. Cox proportional hazard models were used to perform univariate and multivariate analyses. RESULTS: At 5 y, IBIL >7.15 µmol/l were significantly associated with superior progression-free survival (PFS, 83.6% vs 70.3%; P < .001), overall survival (OS, 88.6% vs 80.5%; P = .012), distant metastasis-free survival (DMFS, 90.3% vs 82.8%; P = .006), and locoregional relapse-free survival (LRFS, 92.1% vs 86.4%; P = .048) than IBIL ≤7.15 µmol/l. Similarly, patients with DBIL >2.65 µmol/l had better prognosis across all outcomes than those of patients with DBIL ≤2.65 µmol/l (all P < .05), except no difference was observed in LRFS (90.5% vs. 87.3%, P = .195). Multivariate analyses showed that IBIL >7.15 µmol/l was an independent protective prognostic factor for PFS (HR, 0.57; 95% CI, 0.40-0.81; P = .002), OS (HR, 0.67; 95% CI, 0.43-0.92; P = .041), and DMFS (HR, 0.63; 95% CI, 0.40-0.98; P = .034); while serum DBIL only remained significant for PFS (HR, 0.63; 95% CI, 0.44-0.89; P = .009). CONCLUSIONS: Pretreatment IBIL and DBIL are potentially independent prognostic factors for patients with advanced NPC.

[Effect of Qibai Pingfei capsule medicated serum on protein expressions of KATP channel in pulmonary arterial smooth muscle cells via nitric oxide].

To investigate the ATP-sensitive potassium channel (KATP channel) protein expressions during different periods under hypoxia condition and explore the effect of Qibai Pingfei capsule medicated serum (hereinafter referred to as QBPF) on the correlation between the protein expressions of KATP channel and nitric oxide in rat pulmonary arterial smooth muscle cells(PASMCs). Qibai Pingfei capsules were given to SD rats via continuous gavage for 10 days to obtain QBPF. Primary rats PASMCs were cultured by the direct adherent culture method. Western blot was applied to detect the protein expression levels of KATP channel (Kir6.1 and SUR2B) in PASMCs. Then the noncompetitive inhibitor of NO synthase--Nω-nitro-L-arginine methyl ester(L-NAME) and KATP channel inhibitor--glyburide(GLYB) were applied respectively to evaluate the effect of QBPF on the protein expressions of KATP channel. The protein expressions of Kir6.1 and SUR2B were increased after 6-hour hypoxia treament, peaked at the 24-hour hypoxia treament, and decreased in both 48-hour and 72-hour hypoxia groups. Especially, QBPF could further up-regulate the Kir6.1 and SUR2B protein expressions under 24-hour hypoxia condition; however, such up-regulation effect could be blocked by KATP channel inhibitor GLYB and NO specific inhibitor L-NAME, indicating that QBPF played the role of opening KATP channel. The regulatory mechanism was probably associated with up-regulating KATP channel protein expression via NO relative pathway, involving pulmonary vasodilation, and thus relieving the occurence and development of COPD.

[Qibaipingfei Capsule down-regulate the levels of calcineurin and nuclear factor of activated T-cells isoform c3 (NFATc3) in chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the effect of Qibaipingfei Capsule (QPC) on the expressions of calcineurin (CaN) and nuclear factor of activated T-cells isoform c3 (NFATc3) of rat models with phlegm and blood stasis syndrome of chronic obstructive pulmonary disease (COPD), and to explore the possible mechanism underlying the intervention of QPC in pulmonary vascular remodeling of COPD. METHODS: Sixty male Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, a positive group of nifedipine, a high dose group, a middle dose group and a low dose group of QPC. The rat models with phlegm and blood stasis syndrome of COPD were established by compound methods of forced swimming, smoking and hypoxia. Then the pulmonary function and the pathological alterations of pulmonary vessels were observed. Furthermore, the mRNA and protein levels of CaN and NFATc3 in the lung tissues were determined by real-time quantitative PCR and Western blot analysis. RESULTS: Compared with the normal group, the forced expiratory volume at 0.3 second (FEV0.3), the forced vital capacity (FVC) and FEV0.3/FVC in the model group were significantly reduced, but compared with the model group, the values mentioned above were restored to different extents in the groups of nifedipine and QPC. The lung tissues of the model group showed the thickening of pulmonary vascular wall and the formation of compensating emphysema. The above pathological changes were relieved in all the treatment groups. Compared with the normal group, the expressions of CaN and NFATc3 in the model group were significantly up-regulated in transcription and translation levels. Compared with the model group, these expressions were down-regulated to various degrees in all the treatment groups. CONCLUSION: QPC can decrease the levels of CaN and NFATc3 in the lung tissues of COPD.

Effect of Liuweibuqi capsule, a Chinese patent medicine, on the JAK1/STAT3 pathway and MMP9/TIMP1 in a chronic obstructive pulmonary disease rat model.

OBJECTIVE: To observe effect of Liuweibuqi Capsule, a Traditional Chinese Medicine (TCM), on the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and matrix metalloproteinases (MMPs) in a chronic obstructive pulmonary disease (COPD) rat model with lung deficiency in terms of TCM's pattern differentiation. METHODS: Rats were randomly divided into a normal group, model group, Liuweibuqi group, Jinshuibao group, and spleen aminopeptidase group (n=10). Aside from the normal group, all rats were exposed to smoke plus lipopolysaccharide tracheal instillation to establish the COPD model with lung deficiency. Models were established after 28 days and then the normal and model groups were given normal saline (0.09 g/kg), Liuweibuqi group was given Liuweibuqi capsule (0.35 g/kg), Jinshuibao group was given Jinshuibao capsules (0.495 g/kg), and the spleen group was given spleen aminopeptidase (0.33 mg/kg), once a day for 30 days. Changes in symptoms, signs, and lung histology were observed. Lung function was measured with a spirometer. Serum cytokines were detected using enzyme-linked immunosorbent assay, and changes in the JAK/STAT pathway, MMP-9, and MMPs inhibitor 1 (TIMP1) were detected by immunohistochemistry, RT-PCR, and western blotting, respectively. RESULTS: Compared with the normal group, lung tissue was damaged, and lung function was reduced in the model control group. Additionally, the levels of interleukin (IL)-1beta, gamma interferon (IFN-gamma), and IL-6 were higher, while IL-4 and IL-10 were lower in the model control group than those in the normal group. The expressions of JAK1, STAT3, p-STAT3, and MMP-9 mRNA and protein in lung tissue were higher, and TIMP1 mRNA and protein was lower in the model group compared with the normal group. After treatment, compared with the model group, the expression of inflammatory cytokines was lower in each treatment group, and expressions of JAK/STAT pathway, MMPs were lower. Compared with the positive control groups, the Jinshuibao and spleen aminopeptidase groups, lung function was better, and JAK1, STAT3, and p-STAT3 protein were lower and TIMP1 was higher in the Liuweibuqi group. CONCLUSION: Liuweibuqi capsules can improve the symptoms of COPD possibly by regulating the expression of the JAK1/STAT3 pathway and MMP9/TIMP1.

[Role of Foxp3/Treg and RORγt/Th17 cell imbalance in rat model of chronic obstructive pulmonary disease].

OBJECTIVE: To observe the changes in forkhead/winged helix transcription factor p3(Foxp3), regulatory T cells (Treg), retinoid-related orphan receptor gamma (RORγt) in rat model of chronic obstructive pulmonary disease (COPD). METHODS: Twenty Sprague-Dawley (SD) rats were randomly divided into normal control group and COPD model group, with 10 rats in each group. The COPD model was reproduced by smoke inhalation and tracheal instillation of lipopolysaccharide (LPS), and no such treatment was conducted in normal control group. Twenty-eight days after the model reproduction, the pulmonary function was determined, the pathological changes of lung tissue were observed with haematoxylin-eosin (HE) staining, interleukins (IL-6, IL-10) in serum were detected by enzyme-linked immunosorbent assay (ELISA), CD4⁺ CD25⁺ Foxp3⁺ Treg of peripheral blood was determined by flow cytometry, and the expressions of Foxp3, RORγt, IL-17 protein in lung tissue were assayed by Western Blot. RESULTS: Under light microscope, significal interstitial infiltration of inflammatory cells was found in alveoli and interstitial tissue of the lung, and destruction of alveolar tissue, alveolar wall thinning, and even rupture to fuse into bullae, and bleeding into alveoli in different degress could be observed. Compared with the normal control group, forced vital capacity (FVC), forced expiratory volume in 0.3 second (FEV0.3), FEV0.3/FVC, peak expiratory flow (PEF) in model group were significantly decreased [FVC (mL): 8.04 ± 2.03 vs. 9.97 ± 2.14, FEV0.3 (mL): 6.16 ± 2.23 vs. 8.84 ± 2.12, FEV0.3/FVC: 0.70 ± 0.09 vs. 0.85 ± 0.11, PEF (mL/s): 33.56 ± 4.76 vs. 40.14 ± 5.64, P<0.05 or P<0.01]. Serum IL-6 was obviously increased (ng/L: 93.17 ±20.96 vs. 76.28 ± 13.24, P<0.05), IL-10 was significantly decreased (ng/L: 78.62 ± 15.17 vs. 104.34 ± 19.46, P<0.01), and CD4⁺ CD25⁺ FoxP3(+)Treg was significantly diminished [(2.75 ± 0.83)% vs. (4.16 ± 1.14)%, P<0.01] in model group compared with those in the normal control group. The expression of Foxp3 protein in lung tissue in model group was significantly down-regulated compared with that in the normal control group (gray scale: 0.38 ± 0.15 vs. 0.63 ± 0.11, P<0.01), and RORγt and IL-17 protein expressions were significantly up-regulated [RORγt (gray scale): 0.96 ± 0.23 vs. 0.47 ± 0.11, IL-17 (gray scale): 1.02 ± 0.24 vs. 0.34 ± 0.08, both P<0.01]. Correlation analysis showed that FEV0.3 was positively correlated with Foxp3 (r=0.585, P<0.05), and FEV0.3/FVC was negatively correlated with IL-6 and RORγt (r=-0.655, r=-0.607, both P<0.05). PEF was positively correlated with Treg (r=0.573, P<0.05), and negatively correlated with IL-17 (r=-0.198, P<0.05). IL-6 was negatively correlated with Foxp3(r=-0.603, P<0.05),and positively correlated with RORγt (r=0.588, P<0.05). IL-10 was positively correlated with Treg (r=0.573, P<0.05). Treg was positively correlated with Foxp3 (r=0.607, P<0.05), and negatively correlated with IL-17 (r=-0.569, P<0.05). Foxp3 was negatively correlated with RORγt (r=-0.591, P<0.05). RORγt was positively correlated with IL-17 (r=0.578, P<0.05). CONCLUSIONS: There is a relationship among decreased pulmonary function, inflammation and imbalance of Foxp3/Treg and RORγt/Th17 in COPD.

[Imbalance in the expression of Foxp3, T-bet and GATA-3 is correlated with inflammation of chronic obstructive pulmonary disease].

OBJECTIVE: To observe the change of regulatory T cells(Tregs), fork head-like transcription factor 3 (Foxp3), T box expressed in T cells (T-bet) and GATA binding protein 3 (GATA3) in rat models of chronic obstructive pulmonary disease (COPD). METHODS: Thirty rats were randomly divided into control group and model group (n=15 each). The rats of model group were developed by lipopolysaccharide (LPS) and smoking. Interleukin-4 (IL-4) and γ-interferon (IFN-γ) in serum and bronchoalveolar lavage fluid (BALF) were detected 28 days after modeling by ELISA. Peripheral Tregs were detected by flow cytometry. The expressions of Foxp3, T-bet, GATA gene and protein in lung tissue were observed by reverse transcription PCR and Western blotting, respectively. RESULTS: Compared with the control group, the model group had more serious inflammation in lung tissues, expressed the higher levels of IFN-γ in serum and BALF (P<0.01), T-bet mRNA and protein in lung tissue, and the lower levels of IL-4, CD4⁺ CD25⁺ Treg, CD4⁺ CD25⁺ Foxp3⁺ Treg (P<0.05), Foxp3, GATA-3 mRNA and protein (P<0.01). Correlation analysis showed that there were correlations between T-bet, GATA-3, Foxp3 expressions and IL-4, IFN-γ levels (P<0.05). CONCLUSION: There is a relationship between inflammation and imbalance of in the expression of T-bet, GATA-3, Foxp3 in COPD.

Research on frequency of application with modern Chinese herbal medicine.

OBJECTIVE: To study the relationship between 500 kinds of commonly used Chinese herbal medicine and the classification of their efficacies in Chinese Materia Medica in relation to the common diseases listed in Internal Medicine. METHODS: Database retrieval frequency of the quantitative statistical method was adopted. First, the 8 980 kinds of Chinese herbal medicine recorded in Chinese Materia Medica were used as the original search objects, and 4 493 kinds which were cited in more than five articles were picked out and then rechecked for further title citations. Second, as judged based on the Criterion, the numbers of articles which included the medicines in the line of standards were examined. As a result, 500 species of Chinese herbal medicine were singled out based on their retrieval frequency and were then used for compilation of the classification statistics according to their efficacy and the common diseases in Internal Medicine. RESULTS: From the classification of Chinese medicines, herbs with wide efficiency and a meek nature had higher frequencies, but those which were not appropriate as decoctions had relatively lower frequencies. However, according to the average frequency, the Chinese herbal medicine for nourishing qi and tonifying blood, at 36,346 times and 34,544 times, respectively, were the most commonly used. Analyzed from the frequency of application of the Chinese medicine in the treatment of common diseases, most of the top 10 kinds of Chinese herbal medicine with the highest frequencies generally coincided with the 500 selected medicines. In addition, the Chinese medicines with clear pharmacological efficiency were easily isolated and purified to be made into injections, although other forms are more commonly used. CONCLUSION: The results of the research objectively reflected the current applications of Chinese herbal medicine, and could be used as references in teaching, research, clinical applications, and in compiling and increasing the drugs in textbooks and Pharmacopoeia.