Objective:To explore the effects of quercetin on autophagy and proliferation in HBV-positive liver cancer HCCLM3 cells based on STING signaling and its underlying mechanism.Methods:HCCLM3 cells were treated with quercetin (50 μmol/L or 100 μmol/L), designated as the 50 μmol/L group and 100 μmol/L group, respectively. The inhibitory effect of quercetin on HCCLM3 cells was detected using the CCK-8 method. A scratch assay was conducted to assess the impact of quercetin on the migration ability of HCCLM3 cells. A CCK8 and ROS kit was used to detect the effect of quercetin on the levels of reactive oxygen species in HCCLM3 cells. Western blotting was employed to measure the effect of quercetin on the expression of STING signaling and autophagy-related proteins in HCCLM3 cells. RNA interference technology was used to assess the effects of STING signaling inhibition on the expression of autophagy-related proteins and reactive oxygen species levels in HCCLM3 cells. The combined effects of STING activators and quercetin on HCCLM3 cell proliferation and autophagy were evaluated. The t-test was used to detect data differences between two groups, while ANOVA was employed for comparisons among multiple groups, followed by the SNK- q test for further pairwise comparisons. Results:Compared with the control group, quercetin (50 μmol/L and 100 μmol/L groups) significantly inhibited HCCLM3 cell survival activity in a dose-dependent manner (control group: 100%; 50 μmol/L group: 75.25%; 100 μmol/L group: 50.36%, P<0.01 ). Quercetin inhibited HCCLM3 cell migration in a dose-dependent manner (>2 h, control group: 187.16 μm; 50 μmol/L group: 145.22 μm; 100 μmol/L group: 88.21 μm, P<0.01), which significantly increased intracellular reactive oxygen species (ROS) levels in HCCLM3 cells (control group: 1.00; 50 μmol/L group: 1.565; 100 μmol/L group: 2.175, P<0.01). The phosphorylation level of STING was significantly increased ( P<0.01), and the expression of autophagy-related protein microtubule-related protein 1A/1B light chain 3 (LC3) protein was significantly promoted ( P<0.01). Compared with the quercetin group, the cell viability of the small interfering-STING+quercetin group was increased (quercetin group: 56.3%; small interfering-STING+quercetin group: 85.7%, P<0.05), while the expression of autophagy-related protein LC3 was decreased. Compared with the quercetin group, the cell viability of the quercetin+STING activator group was further decreased (quercetin group: 56.7%; quercetin+STING activator group: 35.4%, P<0.01), and the expression levels of STING and autophagy protein LC3 were significantly increased ( P<0.05). Conclusions:STING signaling-regulated cell autophagy mediates the inhibitory effect of quercetin on the proliferation of HCCLM3 cells, and this effect is enhanced after administration of the STING agonist.

Objective:To explore the effects of quercetin on autophagy and proliferation in HBV-positive liver cancer HCCLM3 cells based on STING signaling and its underlying mechanism.Methods:HCCLM3 cells were treated with quercetin (50 μmol/L or 100 μmol/L), designated as the 50 μmol/L group and 100 μmol/L group, respectively. The inhibitory effect of quercetin on HCCLM3 cells was detected using the CCK-8 method. A scratch assay was conducted to assess the impact of quercetin on the migration ability of HCCLM3 cells. A CCK8 and ROS kit was used to detect the effect of quercetin on the levels of reactive oxygen species in HCCLM3 cells. Western blotting was employed to measure the effect of quercetin on the expression of STING signaling and autophagy-related proteins in HCCLM3 cells. RNA interference technology was used to assess the effects of STING signaling inhibition on the expression of autophagy-related proteins and reactive oxygen species levels in HCCLM3 cells. The combined effects of STING activators and quercetin on HCCLM3 cell proliferation and autophagy were evaluated. The t-test was used to detect data differences between two groups, while ANOVA was employed for comparisons among multiple groups, followed by the SNK- q test for further pairwise comparisons. Results:Compared with the control group, quercetin (50 μmol/L and 100 μmol/L groups) significantly inhibited HCCLM3 cell survival activity in a dose-dependent manner (control group: 100%; 50 μmol/L group: 75.25%; 100 μmol/L group: 50.36%, P<0.01 ). Quercetin inhibited HCCLM3 cell migration in a dose-dependent manner (>2 h, control group: 187.16 μm; 50 μmol/L group: 145.22 μm; 100 μmol/L group: 88.21 μm, P<0.01), which significantly increased intracellular reactive oxygen species (ROS) levels in HCCLM3 cells (control group: 1.00; 50 μmol/L group: 1.565; 100 μmol/L group: 2.175, P<0.01). The phosphorylation level of STING was significantly increased ( P<0.01), and the expression of autophagy-related protein microtubule-related protein 1A/1B light chain 3 (LC3) protein was significantly promoted ( P<0.01). Compared with the quercetin group, the cell viability of the small interfering-STING+quercetin group was increased (quercetin group: 56.3%; small interfering-STING+quercetin group: 85.7%, P<0.05), while the expression of autophagy-related protein LC3 was decreased. Compared with the quercetin group, the cell viability of the quercetin+STING activator group was further decreased (quercetin group: 56.7%; quercetin+STING activator group: 35.4%, P<0.01), and the expression levels of STING and autophagy protein LC3 were significantly increased ( P<0.05). Conclusions:STING signaling-regulated cell autophagy mediates the inhibitory effect of quercetin on the proliferation of HCCLM3 cells, and this effect is enhanced after administration of the STING agonist.

Objective:To explore the correlation between serum levels of interleukin-9 (IL-9), platelet activating factor (PAF), total immunoglobulin E (IgE), interferon γ (IFN-γ), and interleukin-4 (IL-4) in patients with chronic spontaneous urticaria (CSU).Methods:Sixty CSU active phase patients admitted to the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 were selected and included in the CSU active phase group. Based on the 7-day Urticaria Activity Score (UAS7), they were divided into three groups: 15 mild group, 25 moderate group, and 20 severe group; And 19 patients who entered the quiescent phase of the disease after 28 days of standardized antihistamine treatment were included in the CSU quiescent phase group. Another 30 healthy subjects who participated in the physical examination at the same time at our hospital′s physical examination center were selected to be included in the healthy control group. 5 ml of fasting elbow vein blood was collected from CSU active and stationary patients, as well as healthy subjects. The serum levels of IL-9, PAF, total IgE, IFN-γ, and IL-4 were detected using enzyme-linked immunosorbent assay. Pearson correlation test was used to analyze the correlation between serum IL-9, PAF levels and total IgE, IFN-γ, and IL-4 levels in CSU active patients.Results:The serum levels of IL-9, PAF, total IgE, and IL-4 in the CSU active phase group were higher than those in the CSU stationary phase group and healthy control group (all P<0.05), and the serum IFN-γ levels were lower than those in the CSU stationary phase group and healthy control group (all P<0.05). There was no statistically significant difference in the levels of the above indicators between the healthy control group and the CSU stationary group (all P>0.05). The serum levels of IL-9, PAF, total IgE, and IL-4 in the severe group were significantly higher than those in the mild and moderate groups (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild and moderate groups (all P<0.05); The serum levels of IL-9, PAF, total IgE, and IL-4 in the moderate group were significantly higher than those in the mild group (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild group ( P<0.05). Pearson correlation analysis showed that serum IL-9 and PAF levels were positively correlated with serum total IgE and IL-4 levels in CSU active phase patients (IL-9: r=0.726, 0.870, PAF: r=0.788, 0.795, all P<0.01), and negatively correlated with serum IFN-γ levels (IL-9: r=-0.831, PAF: r=-0.816, all P<0.01). Conclusions:The serum levels of IL-9 and PAF in patients with active CSU are elevated and correlated with total IgE, IFN-γ, and IL-4 levels, suggesting that IL-9 and PAF may be related to the occurrence and development of CSU.

Objective:To explore the relationship of serum interleukin (IL) -9 and platelet-activating factor (PAF) levels with serum total immunoglobulin E (IgE) levels, disease severity and disease course in patients with chronic spontaneous urticaria (CSU) .Methods:A total of 60 patients with active CSU were collected from Department of Dermatology, the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 (active CSU group), and divided into mild group, moderate group and severe group according to 7-day urticaria activity score (UAS7). After 28-day standard antihistamine therapy, the patients whose condition became stable were included in the stable CSU group. During the same period, 30 health examinees were included in the healthy control group. Peripheral venous blood samples were collected from the subjects in each group, enzyme-linked immunosorbent assay (ELISA) was performed to detect serum levels of IL-9 and PAF, and immunoturbidimetric assay to detect the serum total IgE level. Correlations of serum IL-9 and PAF levels with serum total IgE levels, UAS7 scores and disease courses were analyzed in patients with CSU. One-way analysis of variance was used for comparisons among multiple groups, least significant difference- t test for multiple comparisons, and Pearson correlation analysis for correlation analysis. Results:Totally, 28 males and 32 females were included in the active CSU group, their age ranged from 11 to 68 years (34.68 ± 8.62 years), and the disease duration ranged from 2 months to 7 years (1.42 ± 0.41 years). In the healthy control group, 14 were males and 16 were females, and their age ranged from 10 to 70 years (35.06 ± 7.89 years). According to UAS7, 12, 26, and 22 patients were diagnosed with mild, moderate and severe CSU respectively, and 22 were included in the stable CSU group after standard treatment. The levels of serum IL-9, PAF and total IgE significantly differed among the active CSU group, stable CSU group and healthy control group (IL-9: 144.34 ± 23.19 vs. 109.25 ± 20.77 vs. 107.23 ± 19.23 pg/ml; PAF: 362.45 ± 51.45 vs. 223.18 ± 32.46 vs. 221.23 ± 28.38 pg/ml; total IgE: 168.12 ± 32.48 vs. 24.04 ± 7.04 vs. 21.76 ± 5.95 IU/ml; F = 38.80, 148.38, 499.12, respectively, all P < 0.001), and were significantly higher in the active CSU group than in the stable CSU group and healthy control group (all P < 0.05), while there was no significant difference between the stable CSU group and healthy control group (all P > 0.05). Pearson correlation analysis showed that the serum IL-9 and PAF levels were positively correlated with serum total IgE levels and UAS7 scores (all P < 0.05), but not correlated with the disease course (both P > 0.05) . Conclusion:Serum IL-9 and PAF levels in patients with active CSU were markedly elevated along with the increase in disease severity, and closely correlated with serum total IgE levels.

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Aggrecans/metabolism* ; Animals ; Cartilage, Articular/metabolism* ; Chondrocytes/pathology* ; Cytoskeletal Proteins/metabolism* ; Mice ; Muscle Proteins/metabolism* ; Osteoarthritis/pathology* ; Temporomandibular Joint/pathology*

OBJECTIVE:To observe therapeutic efficacy and safety of glutamine combined with low molecular weight heparin in the treatment of elderly severe pneumonia (SP).METHODS:In retrospective study,88 SP elderly patients were divided into control group (44 cases) and observation group (44 cases).Based on conventional treatment,control group was given Enteral nutritional suspension via nasal feeding.Observation group was additionally given Alanyl glutamine injection 20 g,dissolved in Amino acid solution with ratio of 1:5 at least and maximum concentration belowing 3.5％,i.v.,once a day+Low molecular weight heparin calcium injection 4 KU/kg subcutaneously,once a day,on the basis of control group.Both groups were treated for 7 d.Clinical efficacies and postoperative recovery (ventilator support time,pulmonary rale disappearance time and ICU hospitalization time) were observed in 2 groups.The levels of IgA,IgG,TNF-a,hs-CRP,APACHE Ⅱ score,coagulation function indexes (APTT,D-D,FIB,PT,PLT),blood gas analysis indexes [pa (CO2),SpO2,Oi,pa (O2)] and receptor for advanced glycation end products (RAGE),the occurrence of ADR before and after treatment were also observed in 2 groups.RESULTS:Total response rate of observation group (90.91％) was significantly higher than that of control group (72.73％),while ventilator support time,pulmonary rale disappearance time and ICU hospitalization time were significantly shorter than control group;the incidence of ADR was significantly lower than control group,with statistical significance (P＜ 0.05).After treatment,the levels of IgA,IgG,Oi,SpO2 and pa (O2) in 2 groups were significantly higher than before treatment,and the observation group was significantly higher than the control group.The levels of TNF-αt,hs-CRP,APACHE Ⅱ score,coagulation function indexes,pa(CO2) and RAGE in 2 groups were significantly lower than before,and the observation group was significantly lower than the control group,with statistical significance (P＜0.05).CONCLUSIONS:Based on conventional treatment,glutamine combined with low molecular weight heparin show significantly effect on elderly SP,effectively improve cellular immune function,coagulation function and blood gas analysis indexes and reduce RAGE level with good safety.

Objective To compare the therapeutic effect between Kirschner wire- loop plating and clavicular hook plate in the treatment of distal clavicle fractures. Methods Forty- two patients with type Neer Ⅱ distal clavicle fracture were selected, among whom 23 patients were treated with Kirschner wire- loop plating (group A), and 19 patients were treated with clavicular hook plate (group B). The operative time, fluoroscopy time, length of incision, intra- operative bleeding volume and hospitalization time etc were recorded. The patients were followed up at 6 weeks, 3 months, 6 months and 12 months after operation. The American shoulder and elbow society (ASES) score was evaluated, and the therapeutic effect was evaluated by Karlsson standard. Results The operative time and fluoroscopy time in group B were significantly lower than those in group A: (63.5 ± 12.4) min vs. (71.5 ± 11.1) min and (3.6 ± 1.9) s vs. (4.8 ± 1.5) s, but the intra- operative bleeding volume, length of incision and cases of postoperative shoulder pain in group A were significantly lower than those in group B:(91.5 ± 18.5) ml vs. (108.7 ± 32.5) ml, (6.6 ± 0.7) cm vs. (11.3 ± 0.9) cm and 2 cases vs. 14 cases, and there were statistical differences (P<0.05 or <0.01). There was no statistical difference in hospitalization time between 2 groups (P>0.05). There was no statistical difference in ASES score at 6 weeks and 3 months after operation between 2 groups (P>0.05); but the ASES score at 6 and 12 months in group A was significantly higher than that in group B: (89.9 ± 12.6) scores vs. (79.7 ± 12.6) scores and (96.1 ± 4.8) scores vs. (86.1 ± 12.4) scores, and there was statistical difference (P<0.05 or <0.01). There was no statistical difference in the cases of good and excellent at 6 weeks, 3 months and 6 months after operation (P>0.05);but the cases of good and excellent at 12 months in group A was significantly more than that in group B:23 cases vs. 13 cases, and there was statistical difference (P<0.05). Conclusions Kirschner wire- loop plating provides a new treatment option for type Neer Ⅱ distal clavicle fractures. It is conducive to decrease the incidence of shoulder pain and improve the range of motion of should joint. Besides, this technology has advantage of small incision, relatively simple operation steps and small damage to the surrounding soft tissues of the acromioclavicular joint. It may be superior to the clavicular hook plate.

Objective To investigate the expression change of RACK1 ,Src and Bcl‐2 in gastric carcinoma tissue and adjacent carcinomatous tissue .Methods Eighty specimens of gastric carcinoma and adjacent carcinomatous tissues in our hospital from Au‐gust 1 ,2011 to February 1 ,2014 were collected .The immunohistochemistry staining and Western blotting methods were adopted to detect the expression of RACK1 ,Src and Bcl‐2 protein in gastric carcinoma and adjacent carcinomatous tissues ,and their correlation was analyzed and performed the statistical analysis by combining with the clinicopathological data .Results The immunohistochem‐istry staining and Western blotting detection displayed that the expression positive rate and expression level of RACK 1 in gastric carcinoma tissue were obviously lower than those in the adjacent carcinomatous tissue ,while the expression positive rate and ex‐pression level of Src and Bcl‐2 in gastric carcinoma tissue were obviously higher than those in the adjacent carcinomatous tissue ,the differences were statistically significant (P<0 .05) .The RACK1 expression in gastric carcinoma tissue was negatively correlated with the Src and Bcl‐2 expression(r= -0 .632 ,-0 .754 ,P<0 .01) ,while Src had no obvious correlation with Bcl‐2 protein(r=0 .217 ,P>0 .05) .Conclusion The expression of RACK1 in gastric carcinoma tissue is significantly decreased ,while the expres‐sions of Src and Bcl‐2 are increased .

Community-based rehabilitation (CBR) is positioned to provide various strategies for people with disabilities for achieving the embracing development of the community. CBR is also the terminal of the three-level rehabilitation service system. This paper analyzed the status of domestic community-based rehabilitation based on the document, discussed the possible problems referred to the international concepts about CBR, and suggested a new service pattern of CBR based on the internet and information technology.