Objective:To investigate the effects of different doses of ionizing radiation on the changes in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS) levels in the intestines of mice.Methods:C57BL/6 mice aged 6-8 weeks were randomly assigned to four groups (0 Gy, 0.1 Gy, 0.2 Gy, and 0.5 Gy; n=10/group) and subjected to single whole-body irradiation using a 60Co γ-ray source at a dose rate of 13 mGy/min. At 20 weeks post-irradiation, jejunal, ileal, and colonic tissues were collected. Immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) were employed to assess mRNA and protein expression of NADPH oxidase components. Hydrogen peroxide (H 2O 2) levels and the expression of Nuclear Factor-kappa B (NF-κB), a transcriptional regulator of Dual Oxidase 2 (DUOX2), were also measured. Results:Compared with the 0 Gy group, mice in the 0.5 Gy group exhibited shortened villus length in the jejunum, villus fusion in the ileum, and increased crypt spacing in the colon, with statistically significant differences ( t=2.48, P < 0.05). No significant differences were observed in other dose groups compared to the 0 Gy group ( P > 0.05).The expression of H 2O 2 in the jejunum, ileum, and colon of the 0.1 Gy group was significantly elevated compared to the 0 Gy group ( t=4.12, 3.12, 3.12; P < 0.05). In the 0.5 Gy group, H 2O 2 expression in the jejunum and colon increased nearly twofold relative to the 0 Gy group ( t=8.67, 8.69; P < 0.05).At 20 weeks post-irradiation, DUOX2 protein expression levels in the jejunum, ileum, and colon were markedly higher in irradiated mice than in the 0 Gy group ( t=3.03, 10.29, 2.74; P < 0.05). DUOX2 mRNA levels in the jejunum, ileum, and colon of the 0.1 Gy group were significantly upregulated compared to the 0 Gy group ( t=12.75, 4.12, 11.14; P < 0.05). Additionally, NOX4 mRNA expression increased in the jejunum of the 0.2 Gy group ( t=4.54, P < 0.05) and in the ileum of the 0.1 Gy group ( t=4.13, P < 0.05).The nuclear factor kappa-B (NF-κB), a transcriptional regulator of DUOX2, showed an upward trend in expression in the jejunum, ileum, and colon of the 0.1 Gy group compared to the 0 Gy group, with statistically significant differences ( t=8.73, 8.18, 7.02; P < 0.05). Conclusion:Low-dose radiation induces long-term effects on the intestinal tract. Specifically, 0.5 Gy irradiation causes mild morphological alterations in the jejunum, ileum, and colon, while 0.1 Gy irradiation promotes the upregulation of DUOX2, a NADPH oxidase, in intestinal tissues.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Objective To report cases of checkpoint inhibitor pneumonitis （CIP） in patients with advanced biliary tract cancer, aiming to provide additional approaches for the assessment, treatment, and monitoring of this condition. Methods Three patients developed oxygen desaturation and interstitial lung lesions during chemotherapy combined with immunotherapy, and were diagnosed with CIP in collaboration with the respiratory department. Antitumor therapy was discontinued in the acute phase, and glucocorticoids were administered, with regular monitoring of disease progression. During follow-up, case 1 developed lung metastasis; case 2 showed improvement; case 3 had concurrent infection and tumor progression. Results Glucocorticoids improved lung lesions and hypoxic symptoms in patients with CIP, but attention should be paid to the potential for concurrent infections and tumor progression. Conclusions Comprehensive assessment and early identification of CIP are crucial for patients with advanced biliary tract cancer. For those with recurrent symptoms after glucocorticoid therapy, timely and accurate adjustment of the treatment regimen is essential.

Objective:To investigate the effects of different doses of ionizing radiation on the changes in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS) levels in the intestines of mice.Methods:C57BL/6 mice aged 6-8 weeks were randomly assigned to four groups (0 Gy, 0.1 Gy, 0.2 Gy, and 0.5 Gy; n=10/group) and subjected to single whole-body irradiation using a 60Co γ-ray source at a dose rate of 13 mGy/min. At 20 weeks post-irradiation, jejunal, ileal, and colonic tissues were collected. Immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) were employed to assess mRNA and protein expression of NADPH oxidase components. Hydrogen peroxide (H 2O 2) levels and the expression of Nuclear Factor-kappa B (NF-κB), a transcriptional regulator of Dual Oxidase 2 (DUOX2), were also measured. Results:Compared with the 0 Gy group, mice in the 0.5 Gy group exhibited shortened villus length in the jejunum, villus fusion in the ileum, and increased crypt spacing in the colon, with statistically significant differences ( t=2.48, P < 0.05). No significant differences were observed in other dose groups compared to the 0 Gy group ( P > 0.05).The expression of H 2O 2 in the jejunum, ileum, and colon of the 0.1 Gy group was significantly elevated compared to the 0 Gy group ( t=4.12, 3.12, 3.12; P < 0.05). In the 0.5 Gy group, H 2O 2 expression in the jejunum and colon increased nearly twofold relative to the 0 Gy group ( t=8.67, 8.69; P < 0.05).At 20 weeks post-irradiation, DUOX2 protein expression levels in the jejunum, ileum, and colon were markedly higher in irradiated mice than in the 0 Gy group ( t=3.03, 10.29, 2.74; P < 0.05). DUOX2 mRNA levels in the jejunum, ileum, and colon of the 0.1 Gy group were significantly upregulated compared to the 0 Gy group ( t=12.75, 4.12, 11.14; P < 0.05). Additionally, NOX4 mRNA expression increased in the jejunum of the 0.2 Gy group ( t=4.54, P < 0.05) and in the ileum of the 0.1 Gy group ( t=4.13, P < 0.05).The nuclear factor kappa-B (NF-κB), a transcriptional regulator of DUOX2, showed an upward trend in expression in the jejunum, ileum, and colon of the 0.1 Gy group compared to the 0 Gy group, with statistically significant differences ( t=8.73, 8.18, 7.02; P < 0.05). Conclusion:Low-dose radiation induces long-term effects on the intestinal tract. Specifically, 0.5 Gy irradiation causes mild morphological alterations in the jejunum, ileum, and colon, while 0.1 Gy irradiation promotes the upregulation of DUOX2, a NADPH oxidase, in intestinal tissues.

Bone metastasis-caused pain （BMP） is a common complication of cancer， and the incidence has been on the rise with the increase in the overall prevalence of cancer， threatening the survival and quality of life of patients. BMP is a kind of special pain with the characteristics of inflammatory pain and neuropathic pain， but is different from the two. Therefore， its pathogenesis is very complicated， and it is of great significance to understand the pathogenesis. The currently available studies mainly focused on osteoclast activation， changes in the bone microenvironment， glial cell activation， spinal cord neuron activation， and miRNA dysregulation. Modern therapies include the three-step analgesics， bisphosphonates， palliative radiotherapy， and interventional therapy for bone metastases， which show definite efficacy in short term. However， the long-term effect is unsatisfactory due to the adverse reactions， addiction， and drug resistance. Studies have shown that traditional Chinese medicine （TCM） has definite curative effect on BMP， which is safe， enhances efficacy， reduces toxicity， and boosts immunity. Moreover， it exerts the effect through multiple components， multiple targets， and multiple pathways. As a result， it has unique advantages in the prevention and treatment of BMP and has become a research focus. This paper summarizes the research on the pathogenesis of BMP， the intervention of TCM （compound Chinese medicine prescriptions， Chinese medicinals， and monomers from Chinese medicinals）， and the mechanisms of TCM， such as inhibiting osteoclast activation， glial cell activation， and spinal cord neuron activation， regulating pain mediators and abnormal expression of microRNA， and anti-tumor， which is expected to further clarify the pathogenesis of BMP and provide ideas and methods for the effective prevention and treatment of BMP with TCM.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*

ObjectiveTo analyze the quality changes of Platycladi Semen before and after the deterioration of moth-eaten and rancidity during storage. MethodFour types samples of Platycladi Semen， including normal， moth-eaten， oxidative rancidity and hydrolytic rancidity， were determined for volatile components， odor， and taste based on headspace solid phase microextraction/gas chromatography-mass spectrometry （HS-SPME/GC-MS） and electronic sensory techniques such as electronic nose and electronic tongue. Volatile components were identified by searching the database and manual comparison， the odor and taste were determined by the response values of the electronic nose and electronic tongue sensors， and the difference between samples before and after deterioration was studied by multivariate statistical analysis. ResultA total of 85 compounds were identified in Platycladi Semen samples. Compared with the normal samples， the number of volatile compounds in samples after hydrolytic rancidity decreased by 5， the number of volatile compounds in samples after moth-eaten and oxidative rancidity increased by 1 and 21， respectively. Aldehydes and acids accounted for majority of types. Among them， the contents of N-hexanoic acid， hexanal and propionic acid in the samples of oxidative rancidity reached 11.49%， 10.21% and 7.52%， which became the key indicators of rancidity. There was significant variance among the odor components corresponding to W1W， W2W and W1S sensors by electronic nose analysis. It was indicated that the value of sourness in deteriorated samples generally increased by mean of electronic tongue analysis. Compared with normal samples， the moth-eaten samples had changed slightly and rancidity samples had changed significantly especially oxidative rancidity samples of volatile components， odor and taste by multivariate statistical analysis. ConclusionIn terms of Platycladi Semen， the oxidative rancidity caused by nature storage for 12 months has the greatest impact on the quality. Therefore， it should be mainly to prevent oxidative rancidity to ensure the quality of Platycladi Semen.

OBJECTIVE：To know about the research status of health utility value obtained by mapping method in pharmacoeconomic evaluation ，and to provide reference for bibliometric study in pharmacoeconomic evaluation . METHODS ： Using“Mapping method ”“Health utility value ”“Cost-utility”“Utility point system ”as Chinese and English keywords ，retrieved from CNKI ，Wanfang database ，PubMed，Medline，Ebsco，Ovid and Wiley database ，empirical journal documents published from the inception to Dec. 31st，2018 about using mapping method to obtain health utility value were collected. The bibliometrics was used to statistically analyze basic information of included literature ，the construction and test of the model ，the type of the best model and so on. RESULTS ：The 124 included documents were all published in English journal. In the construction and testing of the mapping model ，the most frequently used econometric methods ，performance evaluation indicators and model testing methods were ordinary least squares （OLS），mean absolute error （MAE）and residual normality test ，application frequency of which were 97 times（31.60％），89 times（24.93％）and 62 times（21.09％）. There are 117 articles that define the best mapping model ，of which 101 articles（86.32％）have the best direct mapping effect. Most of the non-utility measurement scales adopted specific scales （92 articles，77.97％），and a few literatures adopted the universal scale （26 articles，22.03％）. The most utility measurement scales were 3-level European 5-dimensional health scale （79 articles，66.95％）. CONCLUSIONS ：The domestic empirical researches that use the mapping method to obtain health utility values need to be developed yet. A series of mapping models successfully developed by foreign scholars not only provide the feasibility of using non-utility measurement scales for cost-utility analysis ，but also provide more ideas for China to choose the corresponding econometric methods ，evaluation indicators and mapping methods in the empirical research of the mapping method in the future.

Objective To assess the role of Matrix Metalloproteinase-9 (MMP-9)in rheumatoid arthritis (RA).Methods Peripheral blood from 45 RA patients and 28 healthy individuals (HV)were collected to detect RF and hs-CRP by immuno-turbidimetry,ESR by westergren method and MMP-9 by ELISA.The correlation was analysed between MMP-9 and RF, ESR or hs-CRP,respectively,by pearson correlation analysis.Results Levels of RF,ESR,hs-CRP and MMP-9 were signifi-cantly higher in RA patients than HV group (t=3.93~5.96,P<0.001),respectively.RF high titer patients or patients with a high inflammation response showed a higher MMP-9 levels than the RF low titer or slight inflammation patients (P<0.05).MMP-9 was positively correlated to RF,ESR and hs-CRP in RA patients(P<0.05),respectively.Conclusion MMP-9 maybe a sensitive tool in the diagnosis and management of RA patients.

Aim To construct a lentiviral low expres-sion of miR-139-5 p vector and validate its expression efficiency in H9c2 cells. Method Target sequence was designed according to the sequence of rat miR-139-5p. Oligonucleotide duplex was synthesized and cloned into the lentiviral vector pGC-LV. The recombi-nant lentiviral vector, pHelper 1. 0, and pHelper 2. 0 were co-transfected into 293T cells, packaging virus. Then H9 c2 cells were infected with the supernatant containing lentiviral particles, and its infection effi-ciency and miR-139-5 p expression were determined by fluorescent microscope and real-time quantitative PCR, respectively. Results A lentiviral low expression of miR-139-5p vector was successfully constructed. The infection efficiency in H9c2 cells reached over 95%, and the relative expression of miR-139-5p was significantly down-regulated. Conclusion The lentiviral low expression of miR-139-5p vector is successfully constructed, and the expression of miR-139-5p in infected H9c2 cells is inhibited effectively.