Objective To investigate the relationship between the expression levels of lymphocyte activation gene-3(LAG-3)and pen-traxin-3(PTX3)and the disease severity of the patients with allergic rhinitis(AR).Methods A total of 128 AR patients visited the Department of Otolaryngology,Chengdu Integrated TCM and Western Medicine Hospital from January 2021 to June 2023 were retro-spectively selected as the research subjects(AR group).According to the severity of the condition,the patients were further divided into the mild group(n=40),moderate group(n=42),and severe group(n=46).In addition,80 healthy volunteers who underwent physical examinations in our hospital were selected as the control group.The clinical data such as the gender,age,body mass index(BMI),allergens,and disease onset time of all subjects were recorded and analyzed,and all patients were scored using the Score For Allergic Rhinitis(SFAR).The enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of serum LAG-3 and PTX3 in all subjects.The correlation between the expression levels of serum LAG-3 and PTX3 was analyzed by the Pearson correla-tion analysis.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of serum LAG-3 and PTX3 levels,both individually and in combination,for AR.Results The expression levels of serum LAG-3 in the AR group(468.74±104.32 μg/L)were significantly lower than that in the control group(691.53±184.65 μg/L,t=7.795,P<0.05),while those of ser-um PTX3 in the AR group(24.83±7.54 ng/L)were significantly higher than that in the control group(17.34±5.37 ng/L,t=7.793,P<0.05).The expression levels of serum LAG-3 in the AR patients with positive immunoglobulin(IgE)and SFAR score≥7 were 442.46±92.37 μg/L and 448.27±103.24 μg/L,respectively,which were significantly lower than that in the AR patients with negative IgE(497.61±115.32 μg/L)and SFAR score<7(498.66±112.76 μg/L,P<0.05).While the expression levels of serum PTX3 in the AR patients with positive IgE and SFAR score≥7 were 28.24±8.17 ng/L and 26.43±8.73 ng/L,respectively,which were significantly higher than that in the AR patients with negative IgE(21.08±6.25 ng/L)and SFAR score<7(22.51±6.89 ng/L,P<0.05).Com-pared with the mild group,the expression levels of serum LAG-3 in both the moderate and severe groups were reduced,and that of ser-um LAG-3 in the severe group was significantly lower than that in the moderate group.While the expression levels of serum PTX3 showed an opposite trend,and the levels of serum PTX3 in the severe group were significantly higher than that in the moderate group(P<0.05).The Pearson correlation results showed a significant negative correlation between serum LAG-3 and PTX3 levels in AR pa-tients(r=-0.402,P=0.000).The analysis of the ROC curve showed that the area under the ROC curve(AUCROC),sensitivity,and specificity of the combination of serum LAG-3 and PTX3 in the diagnosis of AR were 0.881,89.80％,and 73.80％,respectively,which were better than that of serum LAG-3 and PTX3 alone.Conclusion The combined detection of serum LAG-3 and PTX3 for the diagnosis of AR has higher clinical application value and may be used to evaluate the severity of the disease.

OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjec-ted to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflam-mation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to ex-amine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Line-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P＜0.05,P＜0.01),while high-density lipopro-tein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P＜0.05,P＜0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P＜0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P＜0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed sig-nificant down-regulation(P＜0.05,P＜0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P＜0.05,P＜0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve ab-normal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.

OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjec-ted to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflam-mation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to ex-amine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Line-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P＜0.05,P＜0.01),while high-density lipopro-tein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P＜0.05,P＜0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P＜0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P＜0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1 β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed sig-nificant down-regulation(P＜0.05,P＜0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P＜0.05,P＜0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve ab-normal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.

Objective To investigate the relationship between the expression levels of lymphocyte activation gene-3(LAG-3)and pen-traxin-3(PTX3)and the disease severity of the patients with allergic rhinitis(AR).Methods A total of 128 AR patients visited the Department of Otolaryngology,Chengdu Integrated TCM and Western Medicine Hospital from January 2021 to June 2023 were retro-spectively selected as the research subjects(AR group).According to the severity of the condition,the patients were further divided into the mild group(n=40),moderate group(n=42),and severe group(n=46).In addition,80 healthy volunteers who underwent physical examinations in our hospital were selected as the control group.The clinical data such as the gender,age,body mass index(BMI),allergens,and disease onset time of all subjects were recorded and analyzed,and all patients were scored using the Score For Allergic Rhinitis(SFAR).The enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of serum LAG-3 and PTX3 in all subjects.The correlation between the expression levels of serum LAG-3 and PTX3 was analyzed by the Pearson correla-tion analysis.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of serum LAG-3 and PTX3 levels,both individually and in combination,for AR.Results The expression levels of serum LAG-3 in the AR group(468.74±104.32 μg/L)were significantly lower than that in the control group(691.53±184.65 μg/L,t=7.795,P<0.05),while those of ser-um PTX3 in the AR group(24.83±7.54 ng/L)were significantly higher than that in the control group(17.34±5.37 ng/L,t=7.793,P<0.05).The expression levels of serum LAG-3 in the AR patients with positive immunoglobulin(IgE)and SFAR score≥7 were 442.46±92.37 μg/L and 448.27±103.24 μg/L,respectively,which were significantly lower than that in the AR patients with negative IgE(497.61±115.32 μg/L)and SFAR score<7(498.66±112.76 μg/L,P<0.05).While the expression levels of serum PTX3 in the AR patients with positive IgE and SFAR score≥7 were 28.24±8.17 ng/L and 26.43±8.73 ng/L,respectively,which were significantly higher than that in the AR patients with negative IgE(21.08±6.25 ng/L)and SFAR score<7(22.51±6.89 ng/L,P<0.05).Com-pared with the mild group,the expression levels of serum LAG-3 in both the moderate and severe groups were reduced,and that of ser-um LAG-3 in the severe group was significantly lower than that in the moderate group.While the expression levels of serum PTX3 showed an opposite trend,and the levels of serum PTX3 in the severe group were significantly higher than that in the moderate group(P<0.05).The Pearson correlation results showed a significant negative correlation between serum LAG-3 and PTX3 levels in AR pa-tients(r=-0.402,P=0.000).The analysis of the ROC curve showed that the area under the ROC curve(AUCROC),sensitivity,and specificity of the combination of serum LAG-3 and PTX3 in the diagnosis of AR were 0.881,89.80％,and 73.80％,respectively,which were better than that of serum LAG-3 and PTX3 alone.Conclusion The combined detection of serum LAG-3 and PTX3 for the diagnosis of AR has higher clinical application value and may be used to evaluate the severity of the disease.

【Objective】 To evaluate the efficacy and safety of plasma-derived human coagulation factor Ⅷ (FⅧ) in the treatment of patients with hemophilia A. 【Methods】 A multi-center and open, SAT(single-arm trials) clinical study was conducted. A total of 54 subjects with hemophilia A were enrolled in 5 research centers. FⅧ was injected according to the subjects' weight, severity of disease and other factors, and the transfusion efficiency of FⅧ activity at 10 min after the first infusion of the first bleeding event was taken as the main efficacy indexes. The improvement scores of bleeding symptoms and signs within 24 h after the first infusion of the first bleeding event were the secondary efficacy indexes. The pathogenic microbial indexes and FⅧ inhibitors were detected on 90(th) and 180(th) day after treatment. 【Results】 The transfusion efficiency of FⅧ activity of 54 subjects at 10 min after the first infusion was 171.9% on average, with median of 169.5%, both higher than the target value of 100%. Within 24 h after the first infusion, the improvement of bleeding symptoms and signs of the subjects were scored, among which 19 cases (35.2%) were "obvious", 35 cases (64.8%) were "good", and the total clinical effective rate reached 100%. Five subjects (9.3%) had six drug-related adverse events. On 90(th) and 180(th) day after treatment, hepatitis B surface antigen, hepatitis C antibody, HIV antibody, treponema pallidum antibody and FⅧ inhibitors were detected, and no negative to positive cases were found. 【Conclusion】 After infusion, the FⅧ preparation can significantly improve the FⅧ activity level in hemophilia A patients in a short period of time, which has high infusion efficiency and can achieve better treatment efficacy, and can also effectively control and relieve bleeding symptoms and signs, with good overall safety.

Objective:To investigate the efficacy and safety of flumatinib in the treatment of imatinib-resistant or imatinib-intolerant patients with chronic phase chronic myelogenous leukemia (CML-CP).Methods:The clinical data of 9 CML-CP patients who received flumatinib after imatinib resistance or intolerance in Jining No. 1 People's Hospital from April 2020 to May 2021 were retrospectively analyzed. Patients were evaluated for the hematologic, cytogenetic and molecular responses, progression-free survival (PFS), event-free survival (EFS), and adverse reactions.Results:Among 9 CML-CP patients, there were 4 imatinib-resistant patients and 5 imatinib-intolerant patients. The median duration of flumatinib exposure was 17 months (1-25 months). Except for 1 case who discontinued flumatinib early due to grade 4 thrombocytopenia and other adverse reactions, 7 of the remaining 8 cases achieved the best response at 3, 6 and 12 months of flumatinib therapy. By the end of follow-up in April 2022, 7, 7 and 6 patients achieved complete cytogenetic response (CCyR), major molecular response (MMR) and molecular response 4.5 (MR4.5), respectively. The median time to achieving CCyR, MMR and MR4.5 was 4.5 months (3-6 months), 12 months (3-12 months) and 15 months (3-21 months), respectively. Within 17 months (11-25 months) of follow-up, 7 of the 9 patients had EFS and 8 patients with continuous flumatinib had PFS. Among 9 patients treated with flumatinib, hematologic adverse reactions were observed in 6 cases, and grade 3-4 hematologic adverse reactions occurred in 2 cases. Non-hematologic reactions events mainly included diarrhea (4 cases), muscle ache (2 cases), fatigue (2 cases) and liver damage (2 cases), which were all grade 1-2.Conclusions:Flumatinib is effective and well tolerated in the treatment of imatinib-resistant or imatinib-intolerant CML-CP patients.

Microplastics pollution has attracted worldwide attention. Compared with the status quo of microplastics pollution in marine environment and other major rivers and lakes, the relevant data of the Yellow River basin is relatively inadequate. The abundance, types, and spatial distribution characteristics of microplastic pollution in the sediments and surface water of the Yellow River basin were reviewed. Meanwhile, the status of microplastic pollution in the national central city and Yellow River Delta wetland was discussed, and the corresponding prevention and control measures were put forward. The results showed that the spatial distribution of microplastics pollution in sediments and surface water of the Yellow River basin increased from upstream to downstream, especially in the Yellow River Delta wetland. There are obvious differences between the types of microplastics in sediment and surface water in the Yellow River basin, which is mainly related to the materials of microplastics. Compared with similar regions in China, the microplastics pollution levels in national key cities and national wetland parks in the Yellow River basin are in the medium to high degree, which should be taken seriously. Plastics exposure through various ways will cause serious impact on aquaculture and human health in the Yellow River beach area. To control microplastic pollution in the Yellow River basin, it is necessary to improve the relevant production standards, laws and regulations, and improve the capacity of biodegradable microplastics and the degradation capacity of plastic wastes.
Humans ; Microplastics ; Plastics ; Water Pollutants, Chemical/analysis* ; Environmental Monitoring/methods* ; Water ; China

Uncovering conserved 3D protein-ligand binding patterns on the basis of functional groups(FGs)shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions.Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature,large-scale identification and evaluation of FG-based 3D binding motifs are still lacking.Here,we propose a computational method,Automatic FG-based Three-dimensional Motif Extractor(AFTME),for automatic mapping of 3D motifs to different FGs of a specific ligand.Applying our method to 233 naturally-occurring ligands,we define 481 FG-binding motifs that are highly conserved across different ligand-binding pockets.Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs.Combinations of FG-binding motifs facilitate the binding of proteins to a wide spectrum of ligands with various binding affinities.Finally,we show that our FG-motif map can be used to nominate FGs that potentially bind to specific drug targets,thus providing useful insights and guidance for rational design of small-molecule drugs.

Objective:To compare the clinical efficacy between puncture assisted by a "TINAVI" orthopaedic robot versus freehand puncture in vertebroplaty for osteoporotic vertebral compression fracture(OVCF) of the upper thoracic vertebra.Methods:A retrospective study was conducted of the 19 patients (20 vertebral bodies) with OVCF of the upper thoracic vertebra who had been treated at Department of Spine Surgery, Honghui Hospital from January 2018 to March 2019 by robotic vertebroplasty (robot group) and of another 21 counterpart patients (21 vertebral bodies) who had been treated by conventional vertebroplasty from January 2016 to December 2017 (freehand group). Puncture was conducted by a "TINAVI" orthopaedic robot in the robotic vertebroplasty but freehand in the conventional vertebroplasty. The robot group had 5 males and 14 females, aged from 62 to 88 years; the freehand group had 6 males and 15 females, aged from 64 to 83 years. The 2 groups were compared in terms of operation time, bone cement volume, postoperative complications (cement leakage, infection and embolism), visual analogue scale (VAS), Oswestry disability index (ODI), anterior height (AH) and kyphosis angulation (KA) of the injured vertebra at day 1 and last follow-up after surgery.Results:The 2 groups were comparable because there were no significant differences between them in the preoperative general data ( P>0.05). Vertebroplasty via unilateral puncture approach was completed uneventfully in the 19 patients (20 vertebral bodies) in the robot group and in the 21 patients (21 vertebral bodies) in the freehand group. The 40 patients were followed up for 6 to 12 months (mean, 8.3 month). The operation time [(37.9±8.2) min], bone cement volume [(2.3±0.9) mL] and rate of cement leakage (10.0%, 2/20) in the robot group were all significantly less or lower than those in the freehand group [(46.2±9.4) min, (4.2±1.3) mL and 42.9% (9/21)] ( P<0.05). No infection or embolism was observed in either group. There were no significant differences between the 2 groups in VAS, ODI, AH or KA of the injured vertebra at day 1 or last follow-up after surgery ( P>0.05). Conclusion:In vertebroplaty for OVCF of the upper thoracic vertebra, compared with conventional freehand puncture, puncture assisted by a "TINAVI" orthopaedic robot can lead to satisfactory clinical efficacy because it reduces operation time, volume of bone cement injection, and thus incidence of bone cement leakage.

Objective:To compare the effect of robot navigation system (Tian Ji robot system) plus 3D printing and traditional C-arm X-ray fluoroscopy in assisting percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP) for treatment of Kümmell disease.Methods:A retrospective case-control study was conducted to analyze the clinical data of 40 patients with Kümmell disease treated at Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine from December 2017 to February 2019, including 12 males and 28 females, with an average age of 56.4 years (range, 42-71 years). In observation group, 20 patients underwent PKP or PVP assisted by the robot navigation system and 3D printing. In control group, 20 patients underwent PKP or PVP assisted by the traditional C-arm X-ray fluoroscopy. The operation time and incidence of complications were observed. The visual analogue scale (VAS), Oswestry disability index (ODI), Cobb angle and anterior vertebral height were compared before operation, 1 day and 3 months after operation.Results:All patients were followed up for 3.5-8.6 months (mean, 6.7 months). The operation time in control group was (32.2±5.8)minutes, compared with (26.7±3.6)minutes in observation group ( P<0.05). The incidence of cement leakage was 0% (0/20) in the observation group and 5% (1/20) in control group ( P>0.05). One day after operation, in observation group and control group, the VAS was (2.1±0.3)points and (3.7±0.8)points, the ODI was 14.3±1.8 and 25.5±5.7, the Cobb angle was (20.6±1.2)° and (22.4±0.6)°, and the anterior height of vertebral body was (21.2±0.8)mm and (17.6±0.7)mm, respectively, showing significant improvement compared with those before operation ( P<0.01). Three months after operation, in observation group and control group, the VAS was (1.8±0.4)points and (2.8±0.8)points, the ODI was 12.3±1.5 and 21.6±2.3, the Cobb angle was (18.1±0.8) ° and (20.5±1.6)°, and the anterior height of vertebral body was (20.1±1.8)mm and (16.8±1.3)mm, showing no significant difference compared with those at day 1 after operation ( P>0.05). There were significant differences in the VAS, ODI, Cobb angle and anterior vertebral height between the two groups 1 day and 3 months after operation ( P<0.01). Conclusion:For Kümmell disease, with assistance with the robot navigation system combined with 3D printing, PKP or PVP can more effectively reduce the pain of patients, improve the quality of life, restore the anterior height of vertebral body, and realize the individualized treatment in comparison with the traditional C-arm X-ray fluoroscopy.