ObjectiveTo evaluate the comprehensive intervention effects of Huangqin Qingre Chubi Capsule （黄芩清热除痹胶囊， HQC） on self-perception of patients （SPP） and immune inflammation in patients with rheumatoid arthritis （RA）， and to explore its potential mechanisms. MethodsClinical data of 452 RA patients were retrospectively collected. Patients were divided into a control group （274 cases）， treated with conventional western medicine， and an observation group （178 cases）， treated with HQC for at least 2 weeks in addition to conventional western medicine. The treatment duration was 2 weeks for both groups. Propensity score matching （PSM） was performed at a ratio of 1∶1 to match patients between groups. SPP including the Chinese version of the short form-36 health survey （SF-36）， self-rating anxiety scale （SAS）， self-rating depression scale （SDS）， visual analog scale （VAS）， and Chinese patient-reported index for rheumatoid arthritis （CPRI-RA）， as well as immune inflammatory indicators， including erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide antibody （anti-CCP）， interleukin-6 （IL-6）， immunoglobulin A （IgA）， immunoglobulin G （IgG）， immunoglobulin M （IgM）， complement C3， and complement C4， were collected before and after treatment. Spearman correlation analysis was used to assess the relationships between SPP and immune inflammatory indicators. Logistic regression， association rule analysis， and mediation analysis were performed to evaluate the effects and potential pathways of HQC on SPP and immune inflammatory indicators. Network pharmacology was applied to identify the active components and core targets of HQC in the treatment of RA， followed by molecular docking verification. In cell experiments， cells were divided into normal group， model group， 20% medicated serum group， and 80 nmol/L control group. Human synovial fibroblasts （FLS） were cultured with complete medium in the normal group， while human rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were cultured in the model group. In the 20% medicated serum group， RA-FLS were cultured with medium containing 20% HQC-medicated serum， and in the 80 nmol/L control group， RA-FLS were cultured with complete medium containing 80 nmol/L methotrexate suspension. After 48 h of culture， cell viability was detected by cell counting kit-8 （CCK-8） assay. Levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and interleukin-10 （IL-10） in the cell supernatant were measured by enzyme-linked immunosorbent assay （ELISA）. Protein levels of matrix metalloproteinase 9 （MMP9）， transcription factor AP-1 subunit （JUN）， vascular endothelial growth factor A （VEGFA）， and C-X-C motif chemokine ligand 8 （CXCL8） were detected by Western Blot， and cell migration ability was evaluated using Transwell assay. ResultsAfter PSM， 178 cases were included in each group. After treatment， SF-36 scores increased， while scores of SAS， SDS， VAS and CPRI-RA， levels of ESR， hs-CRP， IL-6， complement C3， and complement C4 levels decreased in both groups； IgG and IgM levels were also reduced in the observation group （P＜0.05）. Physical functioning （correlation coefficient -0.19， P＜0.05） and social functioning （correlation coefficient -0.18， P＜0.05） of SF-36 were negatively correlated with hs-CRP， while VAS score was positively correlated with hs-CRP （correlation coefficient 0.19， P＜0.05）. HQC showed high associations with improvements in multiple indicators of SPP and immune inflammatory， and acted as a protective factor for the improvement of several SPP； hs-CRP and ESR played partial mediating roles in the improvement of SPP induced by HQC （P＜0.05）. Network pharmacology analysis identified baicalein， quercetin， α1-sitosterol， β-sitosterol， stigmasterol， baicalin， and crocetin as the core active components， and JUN， IL-6， VEGFA， MMP9， IL-1β， and CXCL8 as the core targets. Molecular docking results showed strong binding affinities of quercetin with VEGFA， JUN， MMP9， IL-6， and IL-1β， of baicalin with VEGFA and MMP9， and of wogonin with CXCL8. Cell experiments demonstrated that HQC and methotrexate inhibited RA-FLS viability and migration， reduced levels of IL-1β， IL-6， and IL-8， decreased protein levels of MMP9， JUN， VEGFA， and CXCL8， and increased IL-10 levels （P＜0.05）. ConclusionHQC can improve SPP in RA by regulating immune inflammatory responses. Its mechanism may be related to multi-pathway and multi-target inhibition of synovial cell inflammation and migration.

Objective To investigate the effects of STIP1 homology and U-box containing protein 1(STUB1)on the ubiquitination of glutathione peroxidase 4(GPX4)and ferroptosis in colon cancer cells HCT116,as well as the impact on CD8+T cell-mediated killing of HCT116 cells.Methods HCT116 cells were divided into control group,empty plasmid transfection(pcDNA3.1-vector)group,STUB1 overexpression plasmid transfection(pcDNA3.1-STUB1)group,and co-transfection(pcDNA3.1-STUB1+pcDNA3.1-GPX4)group.Cell proliferation ability was assessed by CCK-8 assay.Clonogenic ability was determined by clone formation assay.Malondialdehyde(MDA)levels in cells were measured using an MDA kit.Intracellular ferrous ion(Fe2+)levels were detected with an Fe2+probe.Changes in mitochondrial membrane potential were detected using JC-1 dye.Protein expression levels of STUB1,solute carrier family 7 member 11(SLC7A11),and GPX4 were determined by western blot.The binding between STUB1 and GPX4 was assessed by co-immunoprecipitation.The effect of STUB1 on GPX4 protein ubiquitination was detected using a ubiquitin antibody.HCT116 cells transfected with different plasmids were co-cultured with human peripheral blood CD8+T cells,and the killing ability of CD8+T cells against HCT116 cells was measured using a lactate dehydrogenase(LDH)kit.Perforin,granzyme,and interferon-γ levels in the co-culture supernatant were determined by ELISA.Results Compared with the control group,the pcDNA3.1-STUB1 group showed decreased cell proliferation ability,mitochondrial membrane potential,and protein expression levels of SLC7A11 and GPX4,along with increased STUB1 protein expression,MDA,Fe2+levels,and GPX4 ubiquitination in HCT116 cells.Compared with the pcDNA3.1-STUB1 group,the pcDNA3.1-STUB1+pcDNA3.1-GPX4 group exhibited increased cell proliferation ability,mitochondrial membrane potential,and expression levels of SLC7A11 and GPX4,along with decreased MDA and Fe2+levels in HCT116 cells.After co-culture of HCT116 cells with CD8+T cells,the pcDNA3.1-STUB1 group showed significantly increased killing rate of CD8+T cells against HCT116 cells,as well as elevated levels of perforin,granzyme,and interferon-γ in the co-culture supernatant compared with the control group.Compared with the pcDNA3.1-STUB1 group,the pcDNA3.1-STUB1+pcDNA3.1-GPX4 group exhibited decreased killing rate of CD8+T cells against HCT116 cells and reduced levels of perforin,granzyme,and interferon-γ in the co-culture supernatant.Conclusion Overexpression of STUB1 promotes GPX4 ubiquitination in colon cancer cells HCT116,induces ferroptosis,and enhances the killing effect of CD8+T cells on HCT116 cells.

Objective To investigate the effects of STIP1 homology and U-box containing protein 1(STUB1)on the ubiquitination of glutathione peroxidase 4(GPX4)and ferroptosis in colon cancer cells HCT116,as well as the impact on CD8+T cell-mediated killing of HCT116 cells.Methods HCT116 cells were divided into control group,empty plasmid transfection(pcDNA3.1-vector)group,STUB1 overexpression plasmid transfection(pcDNA3.1-STUB1)group,and co-transfection(pcDNA3.1-STUB1+pcDNA3.1-GPX4)group.Cell proliferation ability was assessed by CCK-8 assay.Clonogenic ability was determined by clone formation assay.Malondialdehyde(MDA)levels in cells were measured using an MDA kit.Intracellular ferrous ion(Fe2+)levels were detected with an Fe2+probe.Changes in mitochondrial membrane potential were detected using JC-1 dye.Protein expression levels of STUB1,solute carrier family 7 member 11(SLC7A11),and GPX4 were determined by western blot.The binding between STUB1 and GPX4 was assessed by co-immunoprecipitation.The effect of STUB1 on GPX4 protein ubiquitination was detected using a ubiquitin antibody.HCT116 cells transfected with different plasmids were co-cultured with human peripheral blood CD8+T cells,and the killing ability of CD8+T cells against HCT116 cells was measured using a lactate dehydrogenase(LDH)kit.Perforin,granzyme,and interferon-γ levels in the co-culture supernatant were determined by ELISA.Results Compared with the control group,the pcDNA3.1-STUB1 group showed decreased cell proliferation ability,mitochondrial membrane potential,and protein expression levels of SLC7A11 and GPX4,along with increased STUB1 protein expression,MDA,Fe2+levels,and GPX4 ubiquitination in HCT116 cells.Compared with the pcDNA3.1-STUB1 group,the pcDNA3.1-STUB1+pcDNA3.1-GPX4 group exhibited increased cell proliferation ability,mitochondrial membrane potential,and expression levels of SLC7A11 and GPX4,along with decreased MDA and Fe2+levels in HCT116 cells.After co-culture of HCT116 cells with CD8+T cells,the pcDNA3.1-STUB1 group showed significantly increased killing rate of CD8+T cells against HCT116 cells,as well as elevated levels of perforin,granzyme,and interferon-γ in the co-culture supernatant compared with the control group.Compared with the pcDNA3.1-STUB1 group,the pcDNA3.1-STUB1+pcDNA3.1-GPX4 group exhibited decreased killing rate of CD8+T cells against HCT116 cells and reduced levels of perforin,granzyme,and interferon-γ in the co-culture supernatant.Conclusion Overexpression of STUB1 promotes GPX4 ubiquitination in colon cancer cells HCT116,induces ferroptosis,and enhances the killing effect of CD8+T cells on HCT116 cells.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

With the continuously increasing demands of plastic products in the current society, the challenge of disposing plastic waste is constantly increasing, leading to the urgent need of mitigating plastic pollution. As a consequence, much attention has been paid to biodegradable plastics due to their degradability in a bio-active environment under certain conditions. Biodegradable plastics herald vast development potentials and considerable market prospects. The degradation of numerous types of biodegradable plastics will be affected by many factors. A thorough understanding of degradation mechanisms as well as functional microbial strains and enzymes is the key to comprehensive utilization and efficient treatment and disposal of biodegradable plastics. The article summarized the types, properties, advantages and disadvantages, and main applications of common biodegradable plastics. The degradation mechanisms, functional microbial strains and enzymes, as well as the degradation degree and duration under different environmental conditions, were also summarized. This review may help better understand the degradation of biodegradable plastics wastes.
Biodegradable Plastics ; Biodegradation, Environmental

Objective : To investigate the effect of (exchange protein directly activated by cAMP⁃1) on inner ear hair cell injury with noise⁃induced hearing loss and its potential mechanism in rats. Methods : Twenty Specific pathogen⁃free (SPF) Sprague⁃Dawley (SD) rats were randomly divided into normal control group and noise exposure group. The rats of noise exposure were exposed to 4 kHz at 101 dB sound pressure level (SPL) for 8 h. Auditory brainstem responses(ABR) were measured in animals before noise exposure and 24 h after noise exposure. Surface preparation , transmission electron microscopy and immunohistochemistry were performed on cochlea tissuesto elucidate changes in Epac expression in rat after noise exposure. The expression levels of Epac1、Rap1、CaMK⁃ Ⅱ、Bax、Bcl⁃2、cleaved caspase3(CC3) and cleaved caspase9(CC9) were analyzed using Western blot. Results : There was found a stable temporary threshold shift after noise exposure( P < 0. 05) . The missing of outer hair cells occurred after noise exposure(P < 0. 05) . Transmission electron microscopy indicated that the epidermis plate of HCs was partially dissolved , with loss or fusion of stereocilia , some HC organelles showed serious injuries after noise exposure. Epac1 immunostaining intensities were substantially enhanced in OHCs after noise exposure( P < 0. 05) . The expression levels of Epac1 , CaMK⁃ Ⅱ and Rap1 protein were significantly up⁃regulated after noise exposure(P < 0. 05) . The expression level of Bcl⁃2 was significantly down⁃regulated after noise exposure(P < 0. 05) . The expression levels of Bax , CC3 and CC9 were significantly up⁃regulated after noise exposure(P < 0. 05) . Conclusion Epac1 ⁃Rap1 signaling pathway mediates the early pathological damage in noise⁃exposed cochlea , and participates in the regulation of inner ear hair cells apoptosis. Epac1 ⁃Rap1 pathway is expected to become a new target for intervention in noise⁃induced hearing loss.

Objective To evaluate the short-term efficacy,safety and impact on the quality of life of anlotinib in third-line and above treatment for advanced non-small cell lung cancer (NSCLC) patients.Methods All the patients received alotinib 12 mg/d.One cycle was defined as 2 weeks on-treatment followed by 1 week off-treatment until disease progression or treatment intolerance.Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to assess tumor responses.Common Terminology Criteria for Adverse Events (CTCAE) 4.02 was used to assess the adverse events.The European Organization for Research on Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 were used to assess quality of life.Results Among 27 patients in study,no complete response (CR) was found,2 patients (7.4％) achieved partial response (PR),16 patients (59.3％) achieved stable disease (SD),9 patients (33.3％) achieved progressive disease (PD),objective response rate (ORR) was 7.4％,and disease control rate (DCR) was 66.7％.The scores of physical functioning (76.00 ± 10.55 vs.64.44 ± 11.59),emotional functioning (81.67 ± 8.71 vs.76.11 ±6.71) and global health status (48.87 ±7.97 vs.40.56 ± 12.49) of the QLQ-C30 scale after treatment were higher than those before treatment,with statistically significant differences (t =-4.516,P ＜0.001;t=-2.646,P=0.019;t=-3.872,P=0.002).Fatigue (50.37±8.95 vs.40.74±13.86),nausea and vomiting (26.54 ± 16.18 vs.14.20 ± 11.97),loss of appetite [M(QR):33.33 (33.33) vs.33(33.33)] were better than before (t =-2.476,P =0.027;t =-5.036,P ＜0.001;Z =-2.923,P =0.003);pain (28.88 ± 14.23 vs.33.33 ± 13.60) and dyspnea [33.33 (33.33) vs.33.33 (66.67)] scores were lower than before (t =3.674,P =0.003;Z =-3.266,P =0.001).The scores of cough (24.44 ±19.12 vs.45.24 ±20.34),shortness of breath [11.11(22.22) vs.33.33(22.22)] and chest pain [0.00(33.33)vs.33.33 (33.33)] in the QLQ-LC13 scale after treatment were lower than those before treatment,with statistically significant differences (t =4.000,P =0.001;Z =-4.125,P ＜0.001;Z =-1.890,P =0.034);the scores of sore mouth or tongue [0.00(33.33) vs.0.00(0.00)] and hands and feet tingling [33.33(33.33) vs.0.00(0.00)] were higher than before (Z=-2.000,P=0.046;Z=-2.264,P=0.024).Common adverse reactions included hypertension,fatigue,elevated thyroid stimulating hormone,proteinuria,hand-foot syndrome,oral mucositis,hemoptysis,etc,mainly grade 1-2,and they were all improved after the treatments.Conclusion Anlotinib as a third-line and further therapy is positive effected and well tolerated.It can alleviate the clinical symptoms and significantly improve the quality of life of NSCLC patients.

OBJECTIVETo analyze the clinical characteristics of protracted bacterial bronchitis (PBB) in children.

METHODThe clinical data of patients seen from October, 2010 to March, 2014 in Department of Respiratory Diseases of our hospital were retrospectively analyzed. Inclusion criteria were over 4 weeks cough, receiving fiberoptic bronchoscopy, positive bacterial culture and (or) the increased percentage of neutral granulocytes in bronchoalveolar lavage fluid (BALF).

RESULTTwenty eight patients were involved, 26 were male (93%) and two were female (7%). The median age of patients was 8.5 months. The median duration of cough was four weeks. The average length of hospital stay was (8.3 ± 3.9)days. The main clinical feature was wet cough in 28 cases, wet cough with wheezing was seen in 21 cases. The wet cough phase distribution was irregular in 21 cases. The crackles with wheeze (in 21 cases) was main signs of PBB. The percentage of CD3⁻ CD16⁺ 56⁺ cells increased in peripheral blood. The fiberoptic bronchoscopic manifestations of PBB were luminal mucosal edema. Eleven patients also had airway malacia. The neutrophil median in BALF was 0.2. The positive rate of bacterial culture of BALF was 36%. The main bacteria were Streptococcus pneumoniae (50%) and Haemophilus influenzae (30%). The main treatment for PBB patients included amoxycillin/clavulanate potassium and second-generation cephalosporins. The average duration of treatment was (17.3 ± 3.2)days, the prognosis was good.

CONCLUSIONPBB is common in male infants. Persistent wet cough with wheezing was the main characteristic of PBB. PBB is commonly accompanied by immune dysfunction and airway malacia, and the pathogens were Streptococcus pneumoniae and Haemophilus influenzae.

Bacterial Infections ; drug therapy ; pathology ; Bronchitis ; drug therapy ; microbiology ; pathology ; Bronchoalveolar Lavage Fluid ; Bronchoscopy ; Cough ; Female ; Haemophilus influenzae ; isolation & purification ; Humans ; Infant ; Male ; Respiratory Sounds ; Retrospective Studies ; Streptococcus pneumoniae ; isolation & purification