Improvement of astrocytic gap junction involves the anti-depressive effect of celecoxib through inhibition of NF-κB.

CONTEXT: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been shown to exhibit anti-depressive effects in clinical trials. However, the direct mechanism underlying its effect on neuroinflammation remains unclear. Neuroinflammatory reaction from astrocytes leads to depression, and our previous study found that gap junction disorder between astrocytes aggravated neuroinflammatory reaction in depressed mice. OBJECTIVE: To investigate the potential mechanism of celecoxib's effects on astrocytic gap junctions during the central nervous inflammation-induced depression. MATERIALS & METHODS: Stereotaxic injection of lipopolysaccharide (LPS) into the prefrontal cortex (PFC) to establish a model of major depressive disorder (MDD). Celecoxib was administrated into PFC 15 min after LPS injection. The depressive performance was tested by tail suspension test and forced swimming test, and the levels of proinflammation cytokines were determined at mRNA and protein levels. Resting-state functional connection (rsFC) was employed to assess changes in the default mode network (DMN). Additionally, astrocytic gap junctions were also determined by lucifer yellow (LY) diffusion and transmission electron microscope (TEM), and the expression of connexin 43 (Cx43) was measured by western blotting, quantitative polymerase chain reaction, and immunofluorescence. RESULTS: LPS injection induced significant depressive performance, which was ameliorated by celecoxib treatment. Celecoxib also improved rsFC in the DMN. Furthermore, celecoxib improved astrocytic gap junctions as evidenced by increased LY diffusion, shortened gap junction width, and normalized levels of phosphorylated Cx43. Celecoxib also blocked the phosphorylation of p65, and inhibition of p65 abolished the improvement of Cx43. DISCUSSION & CONCLUSION: Anti-depressive effects of celecoxib are mediated, at least in part, by the inhibition of nuclear factor- kappa B (NF-κB) and the subsequent improvement of astrocytic gap junction function.

New Staging Model for Radiation-based Hepatocellular Carcinoma Treatment: A National Multicenter Study.

Background and Aims: The study aimed to create a new staging model for radiotherapy-based treatment for prognostic hepatocellular carcinoma (HCC) classification. Methods: The training cohort comprised 658 patients receiving stereotactic body radiotherapy and external validation cohort comprised 533 patients receiving three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. We established a modified staging system as follows: stage I, solitary nodule without macrovascular invasion, or 2-3 nodules no more than 3.0 cm apart, and performance status (PS) 0-2 (Ia: ALBI-1 grade; Ib: ALBI-2 or 3 grade); stage II: 2-3 nodules with any one nodule more than 3.0-cm apart, or ≥4 nodules, and performance status 0-2 (IIa: ALBI-1 grade; IIb: ALBI-2 grade); stage III: macrovascular invasion, regional lymph node metastasis or distant metastasis, and performance status 0-2 (IIIa: ALBI-1 grade; IIIb: ALBI-2 grade); stage IV: performance status 3-4, or performance status 0-2 with ALBI-3 grade. We analyzed long-term overall survival based on different stages. Results: The staging model showed an excellent ability to discriminate patients according to four stages and seven substages with notably different curves in the training and validation cohort. The median survival decreased from stages I to IV with 63.0 months in stage I (not reached in Ia, and 53.0 months in Ib), 24.0 months in stage II (28.0 months in IIa, and 22.0 months in IIb), 11.0 months in stage III (18.0 months in IIIa, and 9.0 months in IIIb), and less than 9.0 months in stage IV in the training cohort. Conclusions: The modified staging model may provide an alternative for clinical radiation oncologists.

Combining stereotactic body radiotherapy with camrelizumab for unresectable hepatocellular carcinoma: a single-arm trial.

PURPOSE: Stereotactic body radiotherapy (SBRT) may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors. This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab (an anti-PD1 monoclonal antibody) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Patients with uHCC, Child-Pugh A/B liver function, and at least one measurable lesion were enrolled between April 2020 and August 2022. Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks. Palliative SBRT was delivered daily over five fractions per week, with a dose range of 30-50 Gy. The primary endpoints were objective response rate (ORR) and safety. This trial was registered at ClinicalTrials.gov (NCT04193696). RESULTS: Twenty-one patients were enrolled; the median radiation dose was 40 Gy, and the median number of cycles of camrelizumab was five. The ORR was 52.4%. After a median follow-up of 19.7 months, the median progression-free and overall survival were 5.8 and 14.2 months, respectively. The overall survival probability was 85.7% at 6 months, 76.2% at 9 months, and 59.9% at 12 months. All grade 3 treatment-related adverse events (TRAEs) occurred in five patients (23.8%) and were manageable. No grade 4/5 TRAEs were observed. CONCLUSION: Palliative SBRT plus camrelizumab showed promising antitumor activity against uHCC. Toxicities were manageable with no unexpected safety issues. This study provides evidence of a new therapeutic method for the treatment of uHCC.

Efficacy and safety of radiotherapy plus anti-PD1 versus transcatheter arterial chemoembolization plus sorafenib for advanced hepatocellular carcinoma: a real-world study.

BACKGROUND: The combination of transcatheter arterial chemoembolization (TACE) plus sorafenib prolonged progression-free survival (PFS) and overall survival (OS) than sorafenib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of radiotherapy (RT) plus monoclonal antibody against programmed cell death 1 (anti-PD1) versus TACE plus sorafenib for patients with advanced HCC. METHODS: Patients with advanced HCC who treated with RT plus anti-PD1 and TACE plus sorafenib were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety. RESULTS: Between January 2018 to March 2021, 37 patients underwent RT plus anti-PD1 and 41 patients underwent TACE plus sorafenib. The baseline characteristics between the two groups were comparable. The ORR and DCR were significantly higher in the RT + PD1 group than the TACE plus sorafenib group according to RECIST 1.1 (54.05% vs. 12.20%, P < 0.001; 70.27% vs. 46.37%, P = 0.041; respectively) and according to mRECIST (56.76% vs. 31.71%, P = 0.039; 70.27% vs. 46.37%, P = 0.041; respectively). RT plus anti-PD1 provided significantly better PFS (HR, 0.51; 95% CI 0.30-0.86; P = 0.017) than TACE plus sorafenib. Moreover, patients with RT plus anti-PD1 had significantly higher 3-, 6-, and 9-month OS rates than those with TACE plus sorafenib(97.3% vs. 92.30%, P < 0.001; 91.89% vs. 68.60%, P < 0.001; 75.5% vs. 60.60%, P < 0.001; respectively). The median OS was more favorable 17.4 months for the RT + PD1 group and 11.9 months for the TACE plus sorafenib group. No treatment-related death was observed. Grade 3 or more treatment-related adverse events (TRAEs) occurred significantly less in patients in the RT + PD1 group than the TACE plus sorafenib group (29.7% vs. 75.6%, P < 0.001), and all TRAEs were manageable. CONCLUSIONS: In this real-world study, RT plus anti-PD1 showed significantly promising efficacy and manageable safety than TACE plus sorafenib in patients with advanced HCC. Toxicities were manageable, with no unexpected safety signals. The study provides evidence on a new therapeutic method in the treatment of advanced HCC.

Effect of Body Composition on Outcomes in Patients with Hepatocellular Carcinoma Undergoing Radiotherapy: A Retrospective Study.

Computed tomography (CT)-assessed body composition is considered a novel prognostic factor for cancer patients. Owing to the need for new prognostic markers for hepatocellular carcinoma (HCC) patients undergoing radiotherapy, we investigated the impact of body composition on outcomes in this patient population. We retrospectively evaluated 109 HCC patients receiving radiotherapy. The skeletal muscle index, subcutaneous adipose tissue index (SATI), and visceral adipose tissue index within 1 mo, before radiotherapy were assessed based on a single CT image slice at the level of the third lumbar (L3) vertebra. The impact of body composition parameters on progression-free survival (PFS) and overall survival (OS) was assessed. Overall, 62 (56.9%) patients died, and 47 (43.1%) patients experienced recurrence during a median follow-up period of 20.5 mo. Multivariate analysis revealed that SATI was an independent prognostic factor for both PFS (hazard ratio [HR] 0.542, P = 0.025) and OS (HR 0.385, P = 0.005). Patients with high SATI (n = 43) had significantly better PFS (P = 0.0093) and OS (P = 0.032) than those with low SATI (n = 66). CT-assessed SATI is an independent prognostic factor in HCC patients receiving radiotherapy. Further validation is warranted to determine whether this finding can be translated into other study populations.

Chemoradiotherapy Versus Chemotherapy Alone for Advanced Esophageal Squamous Cell Carcinoma: The Role of Definitive Radiotherapy for Primary Tumor in the Metastatic Setting.

Introduction: The role of definitive radiotherapy in advanced esophageal squamous cell carcinoma (ESCC), especially in the metastatic setting, remains unclear. Therefore, we aimed to investigate the efficacy of chemoradiotherapy (CRT) versus chemotherapy (CT) alone in these selected patients. Methods: We retrospectively evaluated 194 newly diagnosed advanced ESCC who underwent definitive CRT or CT alone, including 97 patients with locally advanced and 97 patients with distant metastatic disease. Cumulative overall survival (OS) and progression-free survival (PFS) were evaluated with a log-rank test. Propensity score matching was used to simulate random allocation. In addition, we performed subgroup analysis in the locally advanced and metastatic disease. Results: After matching, 63 well-paired patients were selected. The adjusted median OS (12.5 vs. 7.6 months, p = 0.002) and PFS (9.0 vs. 4.8 months, p = 0.0025) in the CRT group were superior to that in the CT-alone group. Further subgroup analysis revealed that CRT conferred survival benefits to both locally advanced and metastatic cohorts. For patients with distant metastasis, median OS (12.9 vs. 9.3 months, p = 0.029) and PFS (9.9 vs. 4.0 months, p =0.0032) in the CRT group were superior to that in the CT-alone group. In a multivariate Cox regression analysis of the entire cohort, additional definitive radiotherapy was independently associated with better OS (p = 0.041) and PFS (p = 0.007). Conclusions: In both locally advanced and metastatic ESCC, additional definitive-dose radiotherapy was associated with improved clinical outcomes. Therefore, more consideration should be given to its application in the metastatic setting.

[Pollution Characteristics and Risk Assessment of Nutrients and Heavy Metals in Sediments of the Fuhe River Influenced Area, Baiyangdian Lake].

Based on the flow direction of the Fuhe River into Baiyangdian Lake, the impacted area of the Fuhe River was divided into 6 subareas, and sediments from 48 sites were collected in November 2020. The characteristics and risks of sediment nutrients and heavy metal pollution in these six subareas were investigated. The results showed that the average ω(TN), ω(TP), and ω(TOC) were 1841 mg·kg-1, 769 mg·kg-1, and 1.77%, respectively. The major heavy metals were Cd, Cu, Zn, Hg, and Pb, which were 3.73, 1.50, 1.42, 1.31, and 1.31 times the soil background values for Hebei Province, respectively. The TP and heavy metal (Cd, Cu, Zn, Hg, and Pb) content showed a decreasing trend from the Fuhe River estuary to the downstream Zaolinzhuang, whereas the TN and TOC content showed no marked trends. TN, TP, TOC, and heavy metals (Cd, Cu, Zn, Hg, and Pb) were enriched in surface sediments (0-10 cm). The TP content in the surface sediments (0-10 cm) of the Fuhe River estuary, Fuhe River estuary-Nanliuzhuang, and Nanliuzhuang subareas were heavily polluted; the Wangjiazhai and Guangdian subareas were moderately polluted; and the Zaolinzhuang subarea was slightly polluted. Cd and Hg were the major contributors to heavy metal pollution, which were at considerable risk and moderate risk levels, respectively. The heavy metals in surface sediments (0-10 cm) of the Fuhe River estuary, Fuhe River estuary-Nanliuzhuang, and Nanliuzhuang subareas were at a considerable risk level, and the sediments below 30 cm presented a low risk level. The leaching concentrations of heavy metals in sediments from the subarea of severe ecological risk level were far less than the identification standard values of leaching toxicity, suggesting that the sediments can be treated as general waste after dredging.

Pingchuan formula improves allergic asthma in mice through inhibiting nuclear factor-kappa B / mitogen-activated protein kinase signaling pathway.

OBJECTIVE: To examine the role and decipher the mechanism of Pingchuan formula (PCF) in treating allergic asthma. METHODS: The mice were treated with saline, dexamethasone (DXM) and PCF for 1 week after the asthma model was established and their respiratory function including respiratory resistance (RI), pulmonary dynamic compliance (Cdyn) and maximum voluntary ventilation (MVV) were measured. In addition, cellular changes in bronchoalveolar lavage fluid (BALF) and pathological changes in lung biopsy as well as the expression level of -smooth muscle actin (α-SMA), transforming growth factor-beta1 (TGF-α1) in BALF and interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), nuclear factor-kappa B-p65 (NF-κBp65), inhibitor-α of nuclear transcription factor κB (IκBα), p38 mitogen-activated protein kinase (p38MAPK), c-jun n-terminal kinase (JNK) and its phosphorylated proteins in lung tissue were also examined and compared among different groups. RESULTS: Our data suggested that the respiratory functions were significantly improved and the pathological changes ameliorated in the DXM group and the PCF group compared to the model group. Both DXM and PCF effectively decreased the number of eosinophils, lymphocytes, and neutrophils in BAL as well as the secretion of α-SMA and TGF-α1, IL-5, IL-13, while increased the expression of TNF-α and IFN-γ. Furthermore, our study indicated that the NF-κBp65, IκBα, p38MAPK and JNK pathways were inhibited under the treatment of PCF. CONCLUSION: Our data indicated that PCF can attenuate the inflammatory response in asthma through inhibiting the NF-κB/MAPK signaling pathway. This study not only supported the use of PCF in allergic asthma in clinic but also shed light upon afurther understanding of thediseasepathogenesis.

[Distribution Characteristics and Risk Assessment of Antibiotics and Polycyclic Aromatic Hydrocarbons in the Sediments of Desilting Demonstration Area in Baiyangdian Lake].

A total of 22 antibiotics and 16 polycyclic aromatic hydrocarbons(PAHs) in sediments before and after desilting in typical areas(fish ponds and open water) of Baiyangdian Lake were analyzed using HPLC-MS/MS and GC/MS(high performance liquid chromatography and gas chromatography coupled with mass spectrometry), to evaluate their potentially risks to the ecological environment. The results showed that the contents of 22 antibiotics in Baiyangdian Lake sediments ranged from 0 to 52.89 ng·g-1, in which the quinolones content was the highest. After dredging treatment, the average content of antibiotics in Nanliuzhuang open water area decreased from 46.25 ng·g-1 to 9 ng·g-1(80.54% reduction), while the average content of antibiotic(19.07 ng·g-1) in Caiputai remained relatively stable. Therefore, the dredging treatment performed better in removing antibiotics from Naliuzhuang area. The total contents of 16 PAHs in sediments ranged from 23.79 ng·g-1 to 329.40 ng·g-1, in which Naphthalene was the highest(242.02 ng·g-1), while Fluoranthene was the lowest. The average content of PAHs in sediments in Nanliuzhuang decreased from 117.45 ng·g-1 to 50.49 ng·g-1 after dredging, while PAHs in Caiputai(57.98 ng·g-1) remained stable; the 57.01% reduction in PAHs in Nanliuzhuang open water indicated that dredging treatment exhibited stronger effects on PAHs variations in Nanliuzhuang compared to that of Caiputai. In addition, the ecological risk assessment showed that the risk of Enrofloxacin and Norfloxacin was high in area S2 of Nanliuzhuang open water, while PAHs exhibited relatively low ecological risk, in which the Naphthalene in area S1 of Fuhe river posed medium ecological risk while the remaining produced low ecological risks. The results indicated that quinolone antibiotics in sediments of the un-dredged area of Baiyangdian Lake should be monitored due to its higher ecological risk.

A Prospective Study of Liver Regeneration After Radiotherapy Based on a New (Su'S) Target Area Delineation.

BACKGROUND: In this study, we designed a new (Su'S) target area delineation to protect the normal liver during liver regeneration and prospectively evaluate liver regeneration after radiotherapy, as well as to explore the clinical factors of liver regeneration and established a model and nomogram. METHODS: Thirty patients treated with preoperative downstaging radiotherapy were prospectively included in the training cohort, and 21 patients treated with postoperative adjuvant radiotherapy were included in the validation cohort. The cut-off points of each optimal predictor were obtained using receiver-operating characteristic analysis. A model and nomogram for liver regeneration after radiotherapy were developed and validated. RESULTS: After radiotherapy, 12 (40%) and 13 (61.9%) patients in the training and validation cohorts experienced liver regeneration, respectively. The risk stratification model based on the cutoffs of standard residual liver volume spared from at least 20 Gy (SVs20 = 303.4 mL/m2) and alanine aminotransferase (ALT=43 u/L) was able to effectively discriminate the probability of liver regeneration. The model and nomogram of liver regeneration based on SVs20 and ALT showed good prediction performance (AUC=0.759) in the training cohort and performed well (AUC=0.808) in the validation cohort. CONCLUSIONS: SVs20 and ALT were optimal predictors of liver regeneration. This model may be beneficial to the constraints of the normal liver outside the radiotherapy-targeted areas.

[Identification of Dredging Depths Based on Sediment Vertical Distribution Profiles of Total Nitrogen and Total Phosphorus and Their Adsorption-desorption Equilibria].

A dredging demonstration project in the Baiyangdian Lake included open waters and fishing ponds to reduce the internal release of nitrogen and phosphorus from bottom sediments. The dredging depth design was determined by both the sediment vertical distribution profile of total nitrogen and phosphorus, and the sediment adsorption-desorption equilibrium method. The determined dredging depths were very similar and coincident. The dredging depth for the demonstration area of open waters in Nanliuzhuang was identified as(50±10) cm; and the dredging depths for fishing ponds were(30±10) cm in both the Nanliuzhuang and Caiputai demonstration areas. The equilibrium nitrogen(NH4+-N) and phosphorus(SRP) concentrations at zero net sorption or desorption(ENC0 and EPC0) were significantly positively correlated with both exchangeable and total nitrogen and phosphorus in the sediments. The total nitrogen and phosphorus in the sediments were also used to predict the risk of their release from the bottom sediments to the overlying water column. The sediment layers with ENC0 and EPC0 values greater than the NH4+-N and SRP in the overlying water column indicated the sediments act as a source of dissolved nitrogen and phosphorus to the overlying water column in the Nanliuzhuang and Caiputai demonstration areas. Accordingly, the sediment layers with both total nitrogen concentrations greater than 750 mg·kg-1 and total phosphorus concentrations greater than 500 mg·kg-1 should be identified as dredging layers.

Pingchuan formula attenuates airway mucus hypersecretion via regulation of the PNEC-GABA-IL13-Muc5ac axis in asthmatic mice.

BACKGROUND/AIMS: Asthma is a common chronic respiratory disease. It has been reported that Pingchuan formula (PCF) can control asthma attacks by reducing airway inflammation, muscle spasm and mucus secretion. However, PCF's mechanism for reducing airway mucus hypersecretion remains unclear. This study aimed to investigate the effect of PCF on airway mucus secretion in asthmatic mice and to explore changes in the PNEC-GABA-IL13-Muc5ac axis. METHODS: Male Babl/c mice were used to establish the asthma model via sensitisation with OVA. Mice were randomly divided into Normal, OVA, DEX, and PCF groups. After treatment, lung histopathology was observed with H&E and PAS staining. BALF levels of IL-5 and IL-13 were detected using ELISA. The levels of mRNA and protein expression for GAD1, GABAARß1, GABAARα1 and Muc5ac in the lung tissue were measured by RT-PCR and Western blot assays. PNECs were observed with AgNOR staining. RESULTS: PCF treatment effectively reduced goblet cell (P < 0.01) and PNEC (P < 0.05) proliferation, lung tissue inflammation and airway mucus hypersecretion. In addition, PCF also markedly downregulated mRNA and protein expression of GAD1, GABAARß1, GABAARα1 and Muc5ac (P < 0.05, compared with OVA), thus inhibiting the GABA-IL-13 pathway in the lung tissue of asthmatic mice. CONCLUSION: These findings suggest that PCF controls asthma attacks by reducing airway inflammation and mucus hypersecretion via the PNEC-GABA-IL13-Muc5ac axis.

Stereotactic body radiotherapy versus intensity-modulated radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND: It is unclear whether robotic stereotactic body radiotherapy (SBRT) is superior to intensity-modulated radiotherapy (IMRT) in advanced hepatocellular carcinoma (HCC). This study aimed to compare the long-term outcomes of SBRT with those of IMRT in HCCs with portal vein tumor thrombosis (PVTT). METHODS: We retrospectively evaluated 287 HCC patients with PVTT who underwent radiotherapy between January 2000 and January 2017. Of them, 154 and 133 patients were treated with IMRT and SBRT, respectively. Overall survival (OS), progression-free survival (PFS), intrahepatic control (IC), and local control (LC) were evaluated in univariable and propensity-score matched analyses. RESULTS: After matching, 102 well-paired patients were selected. There was no significant difference in the 6-, 12-, 24-, and 60-month cumulative OS (73.5, 42.9, 23.6, 7.6% vs. 72.4, 45.1, 29.8, 13.2%, p = 0.151), PFS (53.9, 29.3, 21.8, 7.5% vs. 54.5, 19.3, 12.0, 9.6%, p = 0.744), IC (61.4, 45.7, 39.0, 26.8% vs. 75.1, 45.8, 35.9, 28.7%, p = 0.144), and LC (85.2, 56.5, 52.1, 47.4% vs. 87.4, 65.2, 62.1, 62.1%, p = 0.191) between the IMRT and SBRT groups. A biologically effective dose assumed at an a/b ratio of 10 (BED10) of ≥ 100 Gy was the optimal cutoff for predicting the OS, PFS, IC, and LC in the patients who received SBRT. CONCLUSIONS: When high-precision tracking technology is available, SBRT appears to be a safe and more time-efficient treatment, achieving comparable OS, PFS, IC and LC to IMRT for local advanced HCC with PVTT. A BED10 ≥ 100 Gy is recommended if tolerated by normal tissue.

Long-Term Survival Analysis of Transarterial Chemoembolization Plus Radiotherapy vs. Radiotherapy for Hepatocellular Carcinoma With Macroscopic Vascular Invasion.

Background: Macroscopic vascular invasion (MVI) is a terminal manifestation of hepatocellular carcinoma (HCC) and carries an extremely poor prognosis. In Chinese and Korean HCC guidelines, transarterial chemoembolization (TACE), or/and radiotherapy (RT) is adopted for treatment of MVI. In the current study, we aimed to compare the long-term outcome of TACE + RT to that of RT alone in patients with local advanced HCC with MVI. Methods: In this retrospective study, 148 treatment-naive patients of HCC with MVI were enrolled. Of the patients enrolled, 49 received TACE + RT treatment, whereas 99 patients received RT alone as a monotherapy. Overall survival (OS), progression-free survival (PFS), and intrahepatic control were evaluated using univariable and propensity score-matched analyses. Results: During follow-up, 126 patients (85.1%) died. The median follow-up time was 55.0 months in the RT group and 57.0 months in the TACE + RT group. The TACE + RT group showed better OS and PFS than the RT group, but intrahepatic control was comparable in these two groups. Of 41 cases well-pairs after propensity score matching, the associations between TACE + RT and better OS and PFS remained (15.0 vs. 8.0 months, and 8.0 vs. 4.0 months, all P < 0.05). The 1-, 2-, 3-, and 5-years OS rates in the TACE + RT group were 56.1, 28.6, 20.8, and 15.7 vs. 31.5%, 13.1%, 9.8%, and 6.7% in the RT group, respectively (P = 0.017). The 6-, 12-, and 24-months rates in the TACE + RT group were 51.2, 39.0, and 23.1% vs. 36.6%, 13.9%, and 11.1% in the RT group, respectively (P = 0.04). Two patients (4.1%) experienced radiation-induced liver disease (RILD), and one (2.0%) experienced RT-related gastrointestinal (GI) bleed in the TACE + RT groups. Nine patients (9.1%) experienced RILD, and two (2.0%) experienced RT-related GI bleed in the RT groups. Conclusion: Transarterial chemoembolization + RT had well-complementarity with no more complications than RT alone, providing a better PFS and OS compared with RT-alone treatment for HCC with MVI.

Impact of UGT2B7 and ABCC2 genetic polymorphisms on mycophenolic acid metabolism in Chinese renal transplant recipients.

AIM: To evaluate genetic variants affecting mycophenolic acid (MPA) metabolism in Chinese renal transplant recipients. METHODS: Total 11 SNPs of UGT1A9, UGT1A8, UGT2B7, ABCC2, ABCG2 and SLCO1B3 were genotyped in 408 Chinese renal transplant recipients. Associations between SNPs and MPA concentration/dose ratio (C0/D) were analyzed using different genetic models. Multivariate linear regression was used to analyze associations between log (C0/D) and clinical factors. Results: After adjustment by clinical factors, UGT2B7 rs7662029 was associated with log (C0/D) using a dominant (p = 0.041) and an additive (p = 0.038) model, ABCC2 rs717620 was associated with log (C0/D) using a recessive model (p = 0.019). Using additive model, SNP-SNP interactions were identified (p = 0.002) between ABCC2 rs717620 and UGT1A9 rs2741049, with interactions (p = 0.002) between ABCC2 rs717620 and UGT1A8 rs1042597. Age, albumin and serum creatinine were associated with log (C0/D). CONCLUSION: rs7662029 and rs717620 may affect MPA pharmacokinetics. SNP-SNP interactions and clinical factors may have significant effects on MPA metabolism.

Nerve growth factor and substance P may be involved in moist exposed burn ointment-mediated chronic refractory wound healing.

Moist exposed burn ointment (MEBO) is becoming increasingly popular in China as it shortens wound-healing time and reduces scar formation. However, its exact mechanism in mediating the wound-healing process is not yet clear. In the present study a total of 90 healthy adult male Wistar rats of specific-pathogen-free grade were divided equally into a control group, wound group, MEBO group, recombinant bovine basic fibroblast growth factor (rb-bFGF) group and sham operation group. Wound healing was observed from the extracted granulation tissues and recorded at three time points on 3, 7 and 14 days. Different levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in tissue homogenate were detected using ELISA. Western blot analysis and quantitative PCR were used to detect the expression of nerve growth factor (NGF), substance P (SP) as well as tyrosine kinase A (TrkA) receptor protein and the corresponding mRNA levels in granulation tissue. It was observed that the wound healing progressed faster in the MEBO and rb-bFGF groups compared with the wound group (P<0.01). TNF-α and IL-6 had an upward-downward trend at three time points, with the wound group demonstrating the most obvious increase (P<0.01). NGF and SP mRNA and protein levels in granulation tissue in MEBO, rb-bFGF and sham operation groups reached their highest levels on day 7 and then decreased on day 14. The expression level of TrkA was also measured simultaneously and its expression pattern was similar to that of NGF and SP. These results suggested that MEBO may promote nerve repair and accelerate wound healing through mediating the expression levels of NGF and SP, as well as TrkA.

[Urban Runoff Phosphorus Removal Pathways in Bioretention Systems].

The role of vegetation and saturated zones in stormwater-dissolved phosphorus (PO43--P) removal was investigated using bioretention microcosms. Nine bioretention columns were dosed with synthetic stormwater under various hydrological conditions and phosphorus loading rates and monitored over a 12-month period. Remarkable phosphorus removal (>90%) was achieved using the mixed filter media of sand and local soil, with or without vegetation. Bioretention columns in which P. alopecuroides was planted could significantly enhance PO43--P removal. The saturated zones could also reduce the effluent PO43--P concentrations, but had no significant effect on total phosphorus removal. Approximately 50% of the input phosphorus retained in the filter media was extracted in the top 0-22.5 cm, where it could be available for uptake by plants. Further, 57.1% to 76.1% of the total phosphorus input recovered in the total plant biomass was stored in the above-ground shoots. Thus, periodic harvesting of shoots can be a sustainable method of phosphorus removal from stormwater bioretention systems.

Therapeutic effects of liver soothing pingchuan formula decoction on experimental asthma in BALB/c mice via regulation of nerve growth factor-tyrosine kinase A pathway.

The present study was designed to investigate the effects of liver soothing pingchuan formula decoction (LSPF) on experimental asthma in BALB/c mice and explore its potential molecular mechanisms. An animal model of asthma was established in BALB/c mice through sensitization and activation with intraperitoneal injection of 10% ovalbumin (OVA)/Al(OH)3 solution in addition to inhalation of a 5% OVA solution. LSPF (300 and 600 mg/kg/day) was initially administered orally prior to activation. Following this, bronchoalveolar lavage fluid (BALF) and lung tissues were collected for histopathalogical examination. Levels of inflammatory cells and cytokines were determined in the BALF, and levels of nerve growth factor (NGF) and tyrosine kinase A (TrkA) in the lung tissues were determined. The results of the present study indicated that increased inflammatory reactions were observed following OVA sensitization (P<0.05), and the expression levels of NGF (P<0.05) and TrkA (P<0.05) were significantly increased, compared with normal mice. Notably, compared with the asthma model group, immunohistochemical results revealed that LSPF treatment suppressed OVA induced inflammatory reactions (P<0.05) and NGF (P<0.05) and TrkA expression levels (P<0.05). In addition, the NGF (P<0.05) and TrkA (P<0.05) were revealed to be downregulated with LSPF treatment from the results of the ELISA and western blotting assay. Overall, the results of the present study demonstrated that LSPF exhibits therapeutic effects on experimental asthma in mice, via downregulation of the NGF-TrkA pathway.

[Effects of Three Bioretention Configurations on Dissolved Nitrogen Removal from Urban Stormwater].

Multiple chemical forms of nitrogen in urban storm water make its management challenging. Three types of bioretention systems were constructed in 2015 with loamy sand as filter media, including a conventional freely drained bioretention (CB), a modified bioretetion incorporated a submerged zone (MB1), and a modified bioretention incorporating a submerged zone with woodchips addition (MB2). This study investigated the role of vegetation, the use of submerged zone and carbon addition in achieving co-optimized dissolved nitrogen removal in bioretention systems. Twelve bioretention columns were monitored over a 12-month period of dosing with synthetic storm water under varying hydrology and nitrogen loading rates. All the studied bioretention systems could achieve very good ammonia removal (more than 95%) at an average inflow ammonia concentration of (5.45±2.21) mg·L-1. The filter media sorption, nitrification and plants uptake were the main removal pathways for incoming ammonia. The effluent nitrate concentrations of the CB, MB1 and MB2 were (4.04±2.64)mg·L-1 (31.3%), (0.84±1.18) mg·L-1 (85.7%), and (0.26±0.48) mg·L-1 (95.6%), respectively, at the average inflow nitrate concentration of (5.88±2.32) mg·L-1. The use of the native species P. alopecuroides, a submerged zone and woodchips addition could effectively decrease the effluent nitrate concentration, reduce the washout and achieve high nitrate removal. Both plants uptake and denitrification were the two major pathways for removal of inflow nitrate. Inflow magnitude, antecedent dry days and inflow nitrate concentration were the main factors influencing the effluent nitrate concentrations for the three bioretention systems. The results highlighted that the bioretention design of the native species P. alopecuroides incorporated a submerged zone with 10% woodchips addition could consistently and effectively remove storm water nitrate under hydrological regime and nitrogen loading rates.

Effect of treatment with geraniol on ovalbumin-induced allergic asthma in mice.

BACKGROUND: Asthma, a complex highly prevalent airway disease, is a major public health problem for which current treatment options are inadequate. OBJECTIVE: To evaluate the antiasthma activity of geraniol and investigate its underlying molecular mechanisms. METHODS: In a standard experimental asthma model, Balb/c mice were sensitized with ovalbumin, treated with geraniol (100 or 200 mg/kg) or a vehicle control, during ovalbumin challenge. RESULTS: Treatment of ovalbumin-sensitized/challenged mice with geraniol significantly decreased airway hyperresponsiveness to inhaled methacholine. Geraniol treatment reduced eotaxin levels in bronchoalveolar lavage fluid and attenuated infiltration of eosinophils induced by ovalbumin. Geraniol treatment reduced TH2 cytokines (including interleukins 4, 5, and 13), increased TH1 cytokine interferon γ in bronchoalveolar lavage fluid, and reduced ovalbumin-specific IgE in serum. In addition, treatment of ovalbumin-sensitized/challenged mice with geraniol enhanced T-bet (TH1 response) messenger RNA expression and reduced GATA-3 (TH2 response) messenger RNA expression in lungs. Furthermore, treatment of ovalbumin -sensitized/challenged mice with geraniol further enhanced Nrf2 protein expression and activated Nrf2-directed antioxidant pathways, such as glutamate-cysteine ligase, superoxide dismutase, and glutathione S-transferase, and enhanced formation of reduced glutathione and reduced formation of malondialdehyde in lungs. CONCLUSION: Geraniol attenuated important features of allergic asthma in mice, possibly through the modulation of TH1/TH2 balance and activation the of Nrf2/antioxidant response element pathway.