Clinical predictors of severe radiation pneumonitis in patients undergoing thoracic radiotherapy for lung cancer.

Background: Severe radiation pneumonitis (RP), one of adverse events in patients with lung cancer receiving thoracic radiotherapy, is more likely to lead to more mortality and poor quality of life, which could be predicted by clinical information and treatment scheme. In this study, we aimed to explore the clinical predict model for severe RP. Methods: We collected information on lung cancer patients who received radiotherapy from August 2020 to August 2022. Clinical features were obtained from 690 patients, including baseline and treatment data as well as radiation dose measurement parameters, including lung volume exceeding 5 Gy (V5), lung volume exceeding 20 Gy (V20), lung volume exceeding 30 Gy (V30), mean lung dose (MLD), etc. Among them, 621 patients were in the training cohort, and 69 patients were in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their predictive power. Overoptimism in the training cohorts was evaluated by four validation methods, including hold-out, 10-fold, leave-one-out, and bootstrap methods, and test cohort was used to evaluate the predictive performance of the model. Model calibration, decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: Severe RP was up to 9.4%. The results of multivariate analysis of logistics regression in all patients showed that patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD) could increase the risk of severe RP, and patients with a better lung diffusion function and received standardized steroids treatment could decrease the risk of severe RP. The three models built by MLR, BSR, and RFR all had good accuracy (>0.850) and moderate κ value (>0.4), and the model 2 built by BSR had the highest area under the receiver operating characteristic (ROC) curve (AUC) in three models, which was 0.958 [95% confidence interval (CI): 0.932-0.985]. The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the model 2 which drew the nomogram. The model 2 included subclinical ILD, diffusing capacity of the lung for carbon monoxide (DLCO), ipsilateral lung V20, and standardized steroid treatment, which could affect the incidence of severe RP. Conclusions: Subclinical ILD, DLCO, ipsilateral lung V20, and with or not standardized steroid treatment could affect the incidence of severe RP. Strict lung dose limitation and standardized steroid treatment could contribute to a decrease in severe RP.

HOXC9 characterizes a suppressive tumor immune microenvironment and integration with multiple immune biomarkers predicts response to PD-1 blockade plus chemotherapy in lung adenocarcinoma.

BACKGROUND: The quest for dependable biomarkers to predict responses to immune checkpoint inhibitors (ICIs) combined with chemotherapy in advanced non-small cell lung cancer remains unfulfilled. HOXC9, known for its role in oncogenesis and creating a suppressive tumor microenvironment (TME), shows promise in enhancing predictive precision when included as a TME biomarker. This study explores the predictive significance of HOXC9 for ICI plus chemotherapy efficacy in lung adenocarcinoma (LUAD). METHODS: Following the bioinformatic findings, assays were performed to ascertain the effects of Hoxc9 on oncogenesis and response to programmed death 1 (PD-1) blockade. Furthermore, a cohort of LUAD patients were prospectively enrolled to receive anti-PD-1 plus chemotherapy. Based on the expression levels, baseline characteristics, and clinical outcomes, the predictive potential of HOXC9, PD-L1, CD4, CD8, CD68, and FOXP3 was integrally analyzed. HOXC9 not only mediated oncogenesis, but also corelated with suppressive TME. CMT167 and LLC cell lines unveiled the impacts of Hoxc9 on proliferation, invasion, and migration. Subsequently, tumor-bearing murine models were established to validate the inverse relationship between Hoxc9 expression and effective CD8+ T cells. RESULTS: Inhibition of Hoxc9 significantly curtailed tumor growth (P<0.05), independent of PD-1 blockade. In patient studies, while individual markers fell short in prognosticating survival, a notable elevation in CD8-positive expression was observed in responders (P=0.042). Yet, the amalgamation of HOXC9 with other markers provided a more distinct differentiation between responders and non-responders. Notably, patients displaying PD-L1+/HOXC9- and CD8+/HOXC9- phenotypes exhibited significantly prolonged progression-free survival. CONCLUSIONS: The expression of HOXC9 may serve as a biomarker to amplifying predictive efficacy for ICIs plus chemotherapy, which is also a viable oncogene and therapeutic target for immunotherapy in LUAD.

Aerobic degradation of parent triisobutyl phosphate and its metabolite diisobutyl phosphate in activated sludge: Degradation pathways and degrading bacteria.

Although organophosphate esters (OPEs) degradation has been widely studied, the degradation of their metabolites is always ignored. Triisobutyl phosphate (TiBP), a typical alkyl-OPEs, is of emerging concern because of its potential ecotoxicity in the environment. This study provides comprehensive understanding about the degradation of TiBP and one of its metabolites, diisobutyl phosphate (DiBP) using activated sludge (AS). The results showed that TiBP and DiBP were degraded mainly through hydrolysis, dehydrogenation, and hydroxylation. The degradation kinetics indicated that DiBP had similar transformation rates to its parent TiBP in AS, highlighting the importance of metabolite DiBP study. Dehydrogenase, hydroxylase, phosphotriesterase, phosphodiesterase, and phosphomonoesterase played an important role in contributing to TiBP and its metabolites degradation via enzyme activity analysis. Besides, the expression of genes encoding these enzymes in bacteria and the relative abundance change of bacterial populations indicated that Sphingomonas and Pseudomonas may be the degrading bacteria of TiBP and Pseudomonas may be the main degrading bacteria of DiBP. This study provides new perspectives for metabolite DiBP and its parent TiBP degradation. It highlights that the formation and degradation of metabolites must be considered into the future researches.

Towards the fate of antibiotics and the development of related resistance genes in stream biofilms.

Antibiotics are ubiquitously found in natural surface waters and cause great harm to aquatic organisms. Stream biofilm is a complex and active community composed of algae, bacteria, fungi and other microorganisms, which mainly adheres to solid substances such as rocks and sediments. The durability and diverse structural and metabolic characteristics of biofilms make them a representative of microbial life in aquatic micrecosystems and can reflect major ecosystem processes. Microorganisms and extracellular polymeric substances in biofilms can adsorb and actively accumulate antibiotics. Therefore, biofilms are excellent biological indicators for detecting antibiotic in polluted aquatic environments, but the biotransformation potential of stream biofilms for antibiotics has not been fully explored in the aquatic environment. The characteristics of stream biofilm, such as high abundance and activity of bacterial community, wide contact area with pollutants, etc., which increases the opportunity of biotransformation of antibiotics in biofilm and contribute to bioremediation to improve ecosystem health. Recent studies have demonstrated that both exposure to high and sub-minimum inhibitory concentrations of antibiotics may drive the development of antibiotic resistance genes (ARGs) in natural stream biofilms, which are susceptible to the effects of antibiotic residues, microbial communities and mobile genetic elements, etc. On the basis of peer-reviewed papers, this review explores the distribution behavior of antibiotics in stream biofilms and the contribution of biofilms to the acquisition and spread of antibiotic resistance. Considering that antibiotics and ARGs alter the structure and ecological functions of natural microbial communities and pose a threat to river organisms and human health, our research findings provide comprehensive insights into the migration, transformation, and bioavailability of antibiotics in biofilms.

Triisobutyl phosphate biodegradation by enriched activated sludge consortia: Degradation mechanism and bioaugmentation potential.

This study investigated the ability of activated sludge (AS) to biodegrade triisobutyl phosphate (TiBP) after acclimation in an AS bioreactor by adding 50 mg/L TiBP. The bioreactor significantly increased the biotransformation rate of TiBP (2.15-12.7 d-1) over two months of acclimation. Seven transformation products (TPs) of TiBP were identified by high-resolution mass spectrometry, and hydrolysis, hydroxylation and dehydrogenation were the major biodegradation pathways of TiBP. TiBP degradation solutions at 0, 3, 7, and 10 h showed significantly toxic effects on zebrafish embryos, while the toxicity of TiBP degradation solutions at 24 h significantly decreased. Pseudomonas was inferred to be a specific bacterial population in the TiBP metabolic microbial consortium (TMMC) that degrades TiBP (p < 0.001). When TMMC (0.5, 1, and 2 gss/L) was introduced into AS, the TiBP biotransformation rates (1.97, 2.05, and 2.26 d-1 at 1.0 mg/L TiBP, and 0.09, 0.11, and 0.83 d-1 at 30.0 mg/L TiBP) were significantly enhanced compared to the control (0.31 and 0.07 d-1) without TMMC inoculation. In general, this study provides new insights into the key species populations that accelerate TiBP degradation and promote the development of TiBP reduction biotechnology in WWTPs.

The association between the ERCC1/2 polymorphisms and radiotherapy efficacy in 87 patients with non-small cell lung cancer.

BACKGROUND: This study sought to investigate the association between the ERCC1/2 single-nucleotide polymorphisms (SNPs) and the efficacy of radiotherapy and prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: We examined 6 SNPs in the ERCC1 and ERCC2 genes in 87 consecutive patients with NSCLC who were treated with definitive radiotherapy. The objective remission rates (ORR), overall survival (OS), and progressive-free survival (PFS) were assessed. A Cox regression analysis was conducted to analyze the independent factors related to death and recurrence. RESULT: Patients with the G allele had better OS than patients with the A allele, and there was a statistical difference between the two groups (30.9 vs. 16.2 months; P=0.003). Patients with the AA genotype had significantly worse OS than patients with the AG or GG genotypes (6.8 vs. 19.8 vs. 30.9 months, respectively; P=0.000). The median PFS of the G allele was 18.9 months, which was significantly better than that of the A allele (P=0.040). The median PFS of patients with the GG genotype, the AG genotype, and the AA genotype was 18.9, 11.3, and 5.1 months, respectively; the difference among the three groups was statistically significant (P=0.019). Patients with the G allele also had better PFS than those with the A allele (18.9 vs. 11.3 months, P=0.040). The multivariate cox proportional hazard analysis showed that the ERCC1 gene rs11615 was an independent survival indicator [HR: 1.623, 95% confidence interval (CI): 1.018-2.591, P=0.042] but not an independent recurrence indicator (HR: 1.497, 95% CI: 0.932-2.404, P=0.095). CONCLUSIONS: The ERCC1 rs11615 SNP may be a potential biomarker for predicting survival prognosis in Chinese NSCLC patients who have undergone definitive radiotherapy. Patients with the G allele had better OS than those with the A allele.

The paeonol target gene autophagy-related 5 has a potential therapeutic value in psoriasis treatment.

BACKGROUND: Paeonol is a potent therapy for psoriasis. This study aimed to screen out paeonol-targeted genes in psoriasis and validate the potential of using paeonol for the management of psoriasis. METHODS: Microarray datasets were obtained from the Gene Expression Omnibus. The differentially expressed genes (DEGs) in the lesional skin samples and the overlapping genes between DEGs and paeonol- and psoriasis-related genes were defined as potential targets for psoriasis. After being treated with si-ATG5 and pc-ATG5, human HaCaT cells were treated with 100 ng/ml IL-22 and 10 ng/ml TNF-α with and without paeonol. Cell proliferation, apoptosis, and expression of interleukin (IL)-6, IL-1ß, Beclin 1, ATG5, and p62 in HaCaT cells were determined using ESLIA, PCR, and Western blot analysis. RESULTS: A total of 779 DEGs were identified in the lesional skin samples compared with the non-lesional tissues. The autophagy-related 5 (ATG5) gene was the only gene that overlapped between the DEGs and genes related to paeonol and psoriasis. Cell proliferation, inflammatory cytokines (IL-6 and IL-1ß), and ATG5 expression were increased in IL-22/TNF-α-stimulated HaCaT (model) cells compared with control. Paeonol treatment rescued all changes. si-ATG5 transfection increased inflammation and apoptosis in model cells compared with controls. pc-ATG5 prevented IL-22/TNF-α-induced changes in HaCaT cells. Also, si-ATG5 decreased p62 and Beclin 1 proteins, while pc-ATG5 increased them both. CONCLUSIONS: ATG5-dependent autophagy plays a crucial role in psoriasis. The ATG5 gene might be a therapeutic target for the management of in vitro psoriasis.

Radiosensitizing effect of c-Met kinase inhibitor BPI-9016M in esophageal squamous cell carcinoma cells in vitro and in vivo.

BACKGROUND: c-Met is the receptor of hepatocyte growth factor (HGF) which plays a key role in inhibiting apoptosis. BPI-9016M is a small-molecule c-Met inhibitor that can promote apoptosis and enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizing potential of BPI-9016M in Eca109 human esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo. METHODS: Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability. Clonogenic survival assay and a murine tumor xenograft in male nude mice were used to evaluate the radiosensitizing effect of BPI-9016M. Apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and flow cytometry experiment. Apoptosis-related proteins were detected by western blot. By evaluating the activation of the ATR-Chk1/ATM-Chk2 pathway to detect radiation-induced DNA double-strand break and homologous recombination repair. BPI-9016M induced a radiosensitizing effect in Eca109 cells and reduced the survival rate of clone formation in vitro. RESULTS: The combination of BPI-9016M with irradiation (IR) significantly delayed the growth of ESCC tumor xenografts than treatment alone (P<0.05). The radiosensitizing effects of BPI-9016M were due to increased apoptosis, such as the up-regulation of cleaved-caspase 3 and 9, down-regulation of mutant P53 and Bcl-2, the decreased of phosphorylation of ATR and ATM, and the inhibition of γ-H2AX accumulation in vitro and in vivo. CONCLUSIONS: These findings indicated that BPI-9016M exerts a radiosensitizing effect and enhances apoptosis by inhibiting homologous recombination DNA repair in irradiated ESCC cells.

Association between IDO activity and prognosis in patients with non-small cell lung cancer after radiotherapy.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in the IDO/kynurenine (Kyn) pathway, converts tryptophan (Trp) into Kyn, and plays a significant role in immune suppression and tumor immune evasion. This study aimed to investigate the association between IDO activity and clinical outcomes in non-small cell lung cancer (NSCLC) patients who underwent radiotherapy (RT). METHODS: Serum Kyn and Trp levels were measured in 104 NSCLC patients by high-performance liquid chromatography at baseline, and the following RT. The correlation between IDO activity, as computed by Kyn: Trp ratios and survival was estimated using Kaplan-Meier curves. Cox proportional hazard models are used in the univariate and multivariate analyses. RESULTS: Both the Kyn levels and Kyn:Trp ratios were reduced after RT at a biologically equivalent dose (BED) of <70 Gy, while these increased at a BED of ≥70 Gy. Post/pre-Kyn levels were positively correlated with an objective response. Patients with a higher Kyn:Trp ratio pre-RT had the worse median progression-free survival (mPFS, 13.5 vs. 24.5 months, P=0.049). Higher post/pre-Kyn:Trp ratios were correlated with improved median overall survival (mOS, 23.8 months vs. not reached, P=0.032). On the multivariate analysis, pre-RT Kyn:Trp and post/pre-Kyn:Trp ratios remained as independent predictive factors for PFS and OS, respectively. CONCLUSIONS: It was proved that RT could alter IDO-mediated immune activity and establish strong correlations between IDO activity and survival outcomes in NSCLC patients treated with RT. These present findings suggest that the profiling of IDO activity might allow for the prompt adjustment of RT doses and better predict patient response to RT.

Ligustrazine nanoparticles nano spray's activation on Nrf2/ARE pathway in oxidative stress injury in rats with postoperative abdominal adhesion.

BACKGROUND: Postoperative abdominal adhesions formation is considered a significant clinical entity implicating the healing process following major pelvic and abdominal surgery, with serious clinical complications and need for substantial health care expenditures. However, setting a physical barrier between the damage site and the neighboring tissues is a convenient and highly valid way to minimize or prevent peritoneal adhesions. The present experimental study evaluated the preventive effect of ligustrazine nanoparticles nano spray (LNNS) on postoperative abdominal adhesion in rats and explored its mechanism. METHODS: Sixty male Sprague Dawley (SD) rats were randomly divided into sham operation group, control group, sodium hyaluronate group and low, medium, and high dose LNNS groups. All groups were prepared with abdominal adhesion models except for the sham operation group. The models were made by opening the abdominal cavity to and filing the serosa in ileocecal junction. The abdominal cavity of rats in the sham operation group were only opened and sutured. The wound surface of rats in the sodium hyaluronate group, low, medium, and high dose LNNS groups were sprayed with sodium hyaluronate gel (0.5 mL/kg) and LNNS (2.5, 5, and 10 mL/kg). Rats in each group were sacrificed 7 days later. Degree of adhesion was evaluated by naked eyes and the pathological sections were scored afterwards. The collagen synthesis in adhesion tissues was detected by Masson's trichrome stain, and the activities of reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) in peritoneal fluid were detected with the method of chromogenic substrate. Levels of TNF-α and IL-1ß in serum, and the protein levels of MCP-1 and MMP-9 in adhesion tissues were detected by ELISA and. immunohistochemistry respectively. RT-PCR and Western blot were utilized to identify the expression levels of Nrf2, heme-oxygenase-1, NQO1 mRNA and protein in adherent intestinal tissues. RESULTS: Compared with the control group, the incidence of postoperative abdominal adhesions decreased in the low, medium and high dose LNNS groups, while the expression of SOD in the peritoneal fluid significantly increased. The expression levels of ROS, MDA and NO were reduced remarkably (P<0.05), so were the expression levels of serum TNF-α and IL-1ß (P<0.01) and the expression of MCP-1 protein in adhesion tissues. The MMP-9 protein expression, and Nrf2, heme-oxygenase-1, NQO1 mRNA and protein expressions increased. CONCLUSIONS: LNNS with medium or high dose can significantly reduce the incidence of postoperative abdominal adhesions, the mechanism of which may be the activation of Nrf2/ARE pathway, resulting in the up-regulation of Nrf2, heme-oxygenase-1, NQO1 and mRNA expression, as well as the levels of TNF-α and IL-1ß in peripheral blood and the expression of MCP-1 protein in adhesion tissues. Meanwhile, the content of MMP-9 protein in adhesion tissues were raised, and oxidative stress and inflammatory response are released.

High PD-L1 expression is associated with a favorable prognosis in patients with esophageal squamous cell carcinoma undergoing postoperative adjuvant radiotherapy.

Previous results on the prognostic value of programmed death-ligand (PD-L)1 expression in patients with esophageal squamous cell carcinoma (ESCC) remain limited and conflicting. The present study aimed to determine whether PD-L1 expression status predicts prognosis in patients with ESCC, particularly in those undergoing different postoperative treatments. Immunohistochemical staining for PD-L1 was performed on surgical specimens that were obtained from 246 patients with ESCC, who underwent surgical treatment but did not undergo preoperative chemotherapy, radiotherapy, targeted therapy or immune therapy. The association of PD-L1 expression with the clinicopathological factors and the association of PD-L1 expression with survival of patients with ESCC, including subgroups of patients undergoing different postoperative treatments (surgery alone, surgery with adjuvant chemotherapy, surgery with adjuvant radiotherapy and surgery with adjuvant chemo-radiotherapy groups), were statistically analyzed. Positive PD-L1 expression was significantly associated with advanced tumor-node metastasis stage (P=0.022). Median overall survival (OS) time was compared between patients with positive PD-L1 expression and those with negative PD-L1 expression in the overall patient population. In patients who were treated with postoperative adjuvant radiotherapy, the prognosis was significantly improved in patients who were PD-L1-positive compared with those who were PD-L1-negative (P=0.046). In patients treated with adjuvant chemotherapy, median OS was poorer in patients with positive PD-L1 expression compared with those with negative PD-L1 expression. However, the difference was not significant. Multivariate Cox regression analysis demonstrated that PD-L1 expression status was not an independent prognostic factor in patients with ESCC. High PD-L1 expression was associated with a favorable prognosis in patients with ESCC undergoing postoperative adjuvant radiotherapy, and it was concluded that patients with positive PD-L1 expression might benefit from postoperative adjuvant radiotherapy.

A retrospective study of shrinking field radiation therapy during chemoradiotherapy in stage III non-small cell lung cancer.

BACKGROUND: and purpose: This retrospective study aimed to investigate the feasibility of shrinking field radiotherapy during chemoradiotherapy in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ninety-seven patients with stage III NSCLC who achieved a good response to chemoradiation were analyzed. Computed tomography was performed after 40-50 Gy dose radiation to evaluate curative effect. Patients in the shrinking field group underwent resimulation CT scans and shrinking field radiotherapy. Acute symptomatic irradiation-induced pneumonia (ASIP), progression patterns and survival were assessed. RESULTS: Of the 97 patients who achieved response after a median total dose of 60 Gy, fifty patients received shrinking field radiotherapy. The incidence of acute symptomatic irradiation-induced pneumonia tended to be lower for the shrinking field group (18.0% vs. 23.4%, P = 0.51). The rate of disease progression was significantly higher in the non-shrinking than shrinking field group (95.7% vs. 66.0%, P < 0.001). Compared to the non-shrinking field group, the shrinking field group had similar overall survival (30.0 vs. 30.0 months, P = 0.58) but significantly better median progression-free survival (14.0 vs. 11.0 months, P = 0.006). CONCLUSIONS: Shrinking field radiotherapy during chemoradiotherapy in stage III non-small cell lung cancer seems safe with acceptable toxicities and relapse, and potentially spares normal tissues and enables dose escalation. Prospective trials are warranted.

Systematic review and meta-analysis of the accuracy of 18F-FDG PET/CT for detection of regional lymph node metastasis in esophageal squamous cell carcinoma.

BACKGROUND: We performed a systematic review and meta-analysis to assess the accuracy of 18F-fluorodeoxyglucose positron emission tomography with computer tomography (18F-FDG PET/CT) for detection of regional lymph node metastasis in esophageal squamous cell carcinoma in per-patient and per-nodal station basis. METHODS: Electronic databases were researched for studies assessing the sensitivity and specificity of PET/CT to detect the regional lymph node metastasis published between January 2006 and December 2017 on esophageal squamous cell carcinoma. STATA software was performed to assess the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd ratio (DOR) and summary receiver operating characteristic (SROC) curve. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Deeks' Funnel Plot Asymmetry Test were performed to evaluate the study quality and publication bias of included studies. RESULTS: Nineteen studies were eligible for meta-analysis, comprising 1,089 patients with esophageal cancer who underwent 18F-FDG PET/CT before surgery. According to the content of the article, we divided the selected studies into per-patient basis group and per-nodal basis group (one of the articles was involved in both groups). For the per-nodal station basis group (12 studies, 5,681 stations), the pooled sensitivity and specificity estimates of 18F-FDG PET/CT for detecting regional lymph node metastasis were 66% [95% confidence interval (CI): 51-78%] and 96% (95% CI: 92-98%), respectively. The corresponding values on a per-patient basis group (8 studies; 506 patients) were 65% (95% CI: 49-78%) and 81% (95% CI: 69-89%) in sensitivity and specificity, respectively. CONCLUSIONS: Overall, 18F-FDG PET/CT have a moderate to low sensitivity and a high to moderate specificity for detection of regional nodal metastasis in esophageal cancer. Therefore, since the false rate is considerable, extending the extent of lymph node dissection or radiotherapy target volume is necessary after diagnosis of regional nodal metastasis by 18F-FDG PET/CT.

[History of incompability among medicinals of "Glycyrrhiza antagonistic to Sargassum, Euphorbia Pekinensis, Kansui, and Genkwa" and its modern recognition].

The allegation of "Glycyrrhiza antagonistic to Sargassum, Euphorbia Pekinensis, Kansui, and Genkwa", being one of the hypotheses of "18 antagonisms" in TCM pharmacology, is referring to the antagonistic action among the Radix et Rhizoma Glycyrrhiza and Radix Euphorbiae Kansui, Radix Euphorbiae Pekinensis, Flos Genkwa, and Sargassum when compounded together in a single recipe. By reviewing its history concerted with modern knowledge, it can be found that the theory of "seven emotions" was originated from Shennong's Classic of Materia Medica; while the Variorum of the Classic of Materia Medica firstly and definitely records that Radix et Rhizoma Glycyrrhizae is forbidden to be used with Radix Kansui, Flos Genkwa, Radix Euphorbiae Pekinensis, Sargassum together in a single formula. It was summarized into a Chinese poetic sentence as above-mentioned later. In the works of later ages, including Chinese Pharmacopoeia, A Great Dictionary of Chinese Materia Medica, and China's Herbology, etc., all enhance the understanding of the prohibited combination of Radix et Rhizoma Glycyrrhizae and its incompatible herbs. Nevertheless, there are discrepancies between the results of modern experimental and clinical studies on this problem, which, needless to say, should be resolved by further investigations.

[Effect of Xianxiong decoction on acute lung injury mice induced by lipopolysaccharide].

OBJECTIVE: To investigate the effect of Xianxiong decoction on the mice with acute lung injury induced by lipopolysaccharide. METHOD: Eighty female ICR mice were randomly divided into 8 groups: model group, Xianxiong decoction group, Daxianxiong decoction group, Xianxiong decoction group without Kansui Radix group, Xianxiong decoction group without Glycyrrhizae Radix et Rhizoma group, Glycyrrhizae Radix et Rhizoma and Kansui Radix group, normal group and control group. Animals of each group, except normal group, were undertaken intraperitoneal injection and intranasal inhalation of lipopolysaccharide (LPS) on day 1, 2, 3 to establish acute lung injury (ALI) model. 30 min after modeling, 0.2 mL corresponding drugs were administrated to each mice, dexam ethasone and normal saline were given to the mice of control group and normal group respectively. White blood cell in blood, neutrophil percentage of blood and bronchoalveolar lavage fluid (BALF) supernatant, the ratio of wet and dry lung tissue ( W/D), histopathological changes of lung tissue were estimated. Sixty ICR mice were randomly divided into normal, model, control, high, middle and low dose Xianxiong decoction groups and were modeled in the same way. ELISA was applied to detect the level of NF-kappaB, TNF-alpha and IL-6 in BALF, PCR for NF-kappaB and TNF-alpha mRNA in lung tissue, and Western blot for NF-kappaB and TNF-alpha. Half of 20 ICR mice were administrated with Xianxiong decoction of its maximum tolerant normal saline. RESULT: Compared with model group, the number of WBC in blood of Xianxiong decoction group mice decreased (P < 0.01), percentage of neutrophils in both blood and BALF decreased as well (P < 0.01, P < 0.05); it also significantly reduced the ratio of W/D (P < 0.01); and found the alveolar wall, the number of inflammatory cells infiltrating improved, compared with model group. Xianxiong decoction reduced the level of NF-kappaB, TNF-alpha and IL-6 in BALF (P < 0.01, P < 0.01, P < 0.05); its high and low dose groups only found TNF-alpha level declined. Five mice died 24 h after administration of Xianxiong decoction which indicated its toxicity when other influential factors were considered. CONCLUSION: Xianxiong decoction is effective on the ALI mice induced by LPS, but it is of toxicity at 3 g x mL(-1).

[Clinical study on aconite prescriptions with incompatible herbs in different areas based on association rules and analysis on compatibility features].

OBJECTIVE: To explore the current application and features of Aconite prescriptions with incompatible herbs in grade A class three hospitals in east China and central China through a clinical study and comparative analysis. METHOD: Clinical prescriptions containing Aconite with incompatible herbs were collected. Association rules were utilized to analyze the compatible features of these herbs. RESULT: This analysis found that the frequently used incompatible herba; pairs are Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma, with the support rate of 44.45%, occupying nearly half of the surveyed prescriptions; Pinelliae Rhizoma is the most frequently used herb in the two areas, with support rate up to 76.24%. Among the top 10 herbal pairs in the support rate, except for Aconiti Lateralis Radix Praeparata and Pinelliae Rhizoma, the top 10 herbs in Central China were mostly for warming the middle jiao and tonifying qi, such as Zingiberis Rhizoma, Atractylodis Macrocephalae Rhizoma and Codonopsis Radix; Whereas those in east China were mostly for activating and nourishing blood, such as Angelicae Sinensis Radix, Chuanxiong Rhizoma, and Salviae Miltiorrhizae Radix et Rhizoma. Among the top 10 herbal pairs in the support rate, except for Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma, the core herbal pairs applied in central China were mainly for resolving phlegm and warming the middle jiao, such as Pinelliae Rhizoma-Glycyrrhizae Radix et Rhizoma, Pinelliae Rhizoma-Zingiberis Rhizoma; Whereas those in east China were principally for activating blood and tonifying qi, like Atractylodis Macrocephalae Rhizoma and Pinelliae Rhizoma, Angelicae Sinensis Radix and Pinelliae Rhizoma. Among the core herbal groups in the two areas, the most frequently used herbal groups in the two areas are Aconiti Lateralis Radix Praeparata, Glycyrrhizae Radix et Rhizoma and Pinelliae Rhizoma with the support rate of 59.73%, accounting for the highest proportion among all of herbal groups. CONCLUSION: There are the combined clinical application of Aconite with incompatible herbs, mostly with Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma, but with differences in the combined application in east China and central China.

Assessment of postoperative adhesion formation in a rat cecum model using different techniques.

Adhesion-related complications after abdominal surgery bring out momentous morbidity and costs. Outcomes from animal experiments investigating prevention of adhesions are limited due to lack of consistency in existing animal models. Different intraperitoneal adhesion models were compared the inter observer variability was evaluated to seek for best model. Forty male SD rats weighting 250-300g were included and assigned randomly to four groups with diverse techniques, (A) postoperative adhesion cecum rat model abraded with sterile rasp; (B) postoperative adhesion cecum rat model abraded with sterile dry gauze; (C) postoperative adhesion cecum rat model abraded with sterile blade; (D) postoperative adhesion cecum rat model abraded with vascular clamp. Macroscopic adhesion scores were evaluated by Bigatti scoring system, and the incidence of adhesion were surveyed on the 7th day after the surgery. The results showed that four techniques currently used Bigatti adhesion scoring system are subjective, the sterile rasp is the most consistent and reproducible tool to establish an intraperitoneal adhesion model which is helpful for related studies and the development of new substances for adhesion prevention in the future.

The effect of Qi'ao Decoction on ovalbumin induced and lipopolysaccharide enhanced severe asthma mice and its mechanism.

AIM: To evaluate the effect of Qi'ao Deocoction (QAD) on the inflammation and hyperresponsiveness of asthma mice. METHODS: 120 Balb/C mice were randomly divided into six groups: normal group, model group, dexamethasone group, high dose QAD group, medium dose QAD group and low dose QAD group. The asthma model was reproduced in Balb/C mice sensitized by ovalbumin, challenged by OVA and LPS. The mice of the normal group were sensitized, challenged and intranasally instilled by PBS. On day 28-34, 6.7, 13.4 and 26.8 g · kg(-1) Qi'ao Decoction were administrated; 0.002 4 g · kg(-1) dexamethasone solution was given to the dexamethasone group; normal and model groups were given the same amount of normal saline. Bronchoalveolar lavage fluid, airway hyperresponsiveness, lung histopathology and cytokines were then collected and analyzed. RESULTS: Compared with normal group, total cellular score, the number of macrophages, lymphocytes, eosinophils and neutrophils of model group significantly increased (P < 0.01). Compared with model group, the administration of dexamethasone induced a significant decrease in eosinophils and neutrophils (P < 0.05, P < 0.01). The number of eosinophils, which plays an important role in airway inflammatory reaction of asthma, of the three QAD groups all decreased (P < 0.01). RL before and after Ach (5 mg · mL(-1)) stimulation in the model group both overtook that in the normal group (P < 0.01). Compared with model group, dexamethasone group, high dose QAD group, medium dose QAD group and low dose QAD group groups all had significantly lower RL before and after Ach stimulation (P < 0.01). Normal pulmonary histopathology was found in the normal group. In the model group, mice exhibited marked increases in inflammatory cell infiltration, mostly including neutrophils and macrophages, perivascular inflammation and thickened alveolus wall (P < 0.01). Dexamethasone application mitigated inflammation around the bronchi (P < 0.05). These histopathological changes were ameliorated in the three decoction groups (P < 0.01, P < 0.05). In addition, alveolus and airway wall lesions of medium dose QAD group and high dose QAD group were reduced, the number of inflammatory cells infiltrated around the walls decreased, no clear degeneration of bronchial epithelial cells was found, and exudates in bronchi declined in different degrees. Compared with normal group, IFN-γ and IL-12 of model group significantly decreased, while IL-4 increased, showing statistic difference (P < 0.05). Compared with model group, IFN-γ and IL-12 level of dexamethasone group went up too, but IL-4 declined (P < 0.05). The level of IFN-γ of medium dose QAD group and high dose QAD group both increased; IL-4 and IL-12 of medium dose group were found significant differences (P < 0.05); but none of the cytokines of low dose QAD group showed statistical significance (P > 0.05). CONCLUSION: QAD can significantly inhibit airway inflammation and airway hyperresponsiveness of mice with severe asthma induced by ovalumin and lipopolysaccharide, adjust the balance of cytokines, and improve lung histopathological condition. So, it exhibits great effect on severe asthma.

[Research on the origins and development of the verse "eighteen antagonism" in Chinese material medica].

The verse "eighteen antagonism" of Chinese materia medica is a kind of describing of drug nature concerning the incompatibility of drugs in compound prescription. Through organizing the medical books in different historical periods, it is found that the drugs in this verse basically coming from TAO Hong-jing's ben cao jing ji zhu (Variorum of Shennong's Classic of Materia Medica), while the style of verse mostly appeared during the Song-Jin-Yuan period was made. The formed verse was explained and supplemented further in the Ming Dynasty, the basis of which appeared in the Song-Jin-Yuan Dynasty, resulting in the increase of the number of antagonistic drugs and lengthy verse. The origin of the verse seen in Ru men shi qin (Confucians' Duties to Their Parents) and those in other books was not identical and was the most popular one after the Qing Dynasty, becoming the most popularly known even today.

Comparative analysis of the main bioactive components of San-ao decoction and its series of formulations.

A high performance liquid chromatographic (HPLC) method with diode array detection (DAD) was established for simultaneous determination of seven main bioactive components in San-ao decoction and its series of formulae (San-ao decoction, Wu-ao decoction, Qi-ao decoction and Jia-wei San-ao decoction). Seven compounds were analyzed simultaneously with a XTerra C(18) column (4.6 mm × 250 mm, 5 µm) using a linear gradient elution of a mobile phase containing acetonitrile (A) and a buffer solution (0.02 mol/L potassium dihydrogen phosphate and adjusted to pH 3 using phosphoric acid) (B); the flow rate was 1.0 mL/min. The sample was detected with DAD at 210, 254 and 360 nm and the column was maintained at 30 °C. All the compounds showed good linearity (r2 > 0.9984) in the tested concentration range. The precisions were evaluated by intra-day and inter-day tests, and relative standard deviation (R.S.D.) values within the range of 0.83%–2.53% and 0.64%–2.77% were reported, respectively. The recoveries of the quantified compounds were observed to cover a range from 95.34% and 104.82% with R.S.D. values less than 2.72%. The validated method was successfully applied for the simultaneous determination of seven main bioactive components including ephedrine (1), amygdalin (2), liquiritin (3), benzoic acid (4), isoliquiritin (5), formononetin (6) and glycyrrhizic acid (7) in San-ao decoction and its series of formulae. The results also showed a wide variation in the content of the identified active compounds in these samples, which could also be helpful to illustrate the drug interactions after some herbs combined in different formulations.