Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.

Aim To investigate the effect of dipeptidyl peptidase-4 inhibitor(DPP-4i)on serum creatinine(Cr)in patients with type 2 diabetes mellitus(T2DM).Methods A systematic search was performed across data-bases of PubMed,Embase,Cochrane Library and Web of Science,and randomized controlled trials(RCT)of DPP-4i therapy for regulating Cr in T2DM patients was included.A fixed-effect or random-effect model was used for data fitting,heterogeneity was quantitatively evaluated according to the index of I2,and sensitivity analysis and publication bias testing were performed by using the standard methods.Results After searching the database through the system,12 RCTs were included,with a total of 2 276 participants.Due to the potential heterogeneity,a random effect model was used for data fitting.DPP-4i treatment could mildly increase Cr levels in T2DM patients(WMD:0.15 mg/L,95％CI:0.03～0.27,I=1 8％,P=0.02),and the results showed statistical differences.According to sensitivity testing,the results of Meta-analysis were relatively reliable.No publication bias was observed according to Begg's and Egger's tests.Conclusions The use of DPP-4i for hypoglycemic treatment in T2DM patients may result in mild elevation of blood Cr lev-els.Further multicenter studies with larger samples are needed in the future to explore the clinical significance of DPP-4i treatment induced changes in Cr levels.

Objective Developing a new type of full-face respiratory protective mask for nuclear facility sites to enhance the sound transmission function and improve the facial adaptability. Methods Combined with feedback from on-site practical needs, this study utilized finite element simulation and ergonomic design methods to investigate the voice transmission units of full-face masks and the facial features of workers at key nuclear facilities. Based on the research results, a new full-face respiratory protection mask structure was designed. Results The optimized structure of passive thin film voice transmission unit significantly enhanced voice transmission efficiency, reducing average voice transmission loss by approximately 70% compared to the control group using thin plate units of equivalent thickness. The existing facial feature test panels insufficiently cover and unevenly classify the facial features of workers at key nuclear facilities. In this study, a specialized test panel based on measurement data achieved a total coverage of 98.5% with high distribution uniformity within each class, providing effective guidance for redesigning full-face mask structural parameters. In comparison to foreign products currently utilized in nuclear facilities, the newly designed full-face mask structure exhibited excellent tightness and structural safety and reliability, and can be cleaned, decontaminated, and reused. Conclusion The results of this study provide significant guidance for improving and optimizing full-face respiratory protection mask used at nuclear facilities, as well as promoting domestic production of high-quality full-face respiratory protection masks.

Objective To analyse the differential metabolites and related metabolic pathways in stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome by serum metabolomics.Methods This study observed 60 patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome and 60 healthy volunteers in the same period.Liquid chromatography-mass spectrometry(LC-MS)was performed on the serum metabonomics.The differential metabolites were identified by multivariate statistical analysis of the original spectrogram and original data,and enrichment analysis of KEGG metabolic pathway was analyzed.Results A total of 60 patients in the group of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome participated in the study,and a total of 60 healthy volunteers in the control group participated in the study.There was no statistical difference in general information and biochemical indicators between the two groups(P>0.05);Eighteen differential metabolites were found respectively,including phenylacetaldehyde,orthophosphate,guanosine,diethyl phosphate,2-dehydro-d-gluconate,guanine and 5-(2-hydroxyethyl)-4-methylthiazole down-regulated expression,taurocholate,2-propylglutaric acid,8-amino-7-oxononanoate,l-tyrosine,s-sulfo-l-cysteine,cyclohexanecarboxylic acid,porphobilinogen,(r)-acetoin,octanoylglucuronide,melatonin and solanine up-regulated expression,involving phenylalanine metabolism,thiamine metabolism,purine metabolism.Conclusion The differential metabolites reveal the metabolic essence of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome from the micro level,and can provide clues for clinical early warning of patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndromet.

ObjectiveTo investigate the moderating effect of psychological resilience in relation to depressive symptoms and suicidal risk among adolescents. MethodsThe research is a descriptive survey. A total of 71 137 adolescents were selected from 163 schools in Deyang by stratified cluster sampling. Their psychological resilience， depressive symptoms and suicide risks were measured oneline by using 10-item Connor-davidson Resilience Scale （CD-RICS-10）， Patients’ Health Questionnaire Depression Scale-9 item （PHQ-9） and Suicidal Behaviors Questionnaire-Revised （SBQ-R）. The moderating effect of psychological resilience in relation to depressive symptoms and suicidal risk was examined by multivariate stratified regression analysis. Results① The score of CD-RISC-10 was negatively related to PHQ-9 score and SBQ-R score （r=-0.305， -0.268， P<0.01）. ② Psychological resilience significantly moderated the relationship between depressive symptoms and suicidal risk （β=-0.100， t=-31.716， P<0.01）. ③ In both male and female adolescents， resilience played a significant role in depressive symptoms and suicide risk （β=-0.086， -0.084， t=-17.502， -18.839， P<0.01）. ConclusionPsychological resilience could significantly alleviate the impact of high-level depressive symptoms on suicidal risk among adolescents， and this effects both male and female adolescents.

Objective:To explore the occurrence and characteristics of adverse reactions related to bevacizumab (Bev) in treatment of non-small cell lung cancer (NSCLC).Methods:The medical records of NSCLC patients treated with Bev in the Respiratory Department of Bozhou Hospital of Traditional Chinese Medicine from May 2019 to March 2021 were collected. Patients with Bev-related adverse reactions, which were judged by Naranjo scoring method, were selected. The relevant information in these patients was extracted from their medical records, and the occurrence and outcomes of the adverse reactions (incidence, time of occurrence, clinical manifestation, severity, etc.) were analyzed retrospectively. The dosing regimen of Bev was IV infusion of 7.5 mg/kg once per 21 days (1 cycle).Results:A total of 142 patients were included in the analysis, and 17 (12.0%), 20 (14.1%), 51 (35.9%), 35 (24.6%), and 19 (13.4%) patients received 1, 2, 3, 4, and 5 cycles of Bev treatment, respectively. All patients were treated with combination regimen with traditional chemotherapy drugs, including pemetrexed in 10 patients (7.0%), pemetrexed+carboplatin in 41 patients (28.9%), and pemetrexed+cisplatin in 91 (64.1%) patients, respectively. Among the 142 patients, 49 (34.5%) had adverse reactions, which were classified as grade 1, 2, 3, and 4 in severity in 18, 19, 6, 6 patients respectively, and the incidence of serious adverse reactions (≥ grade 3) was 8.5% (12/142). The clinical manifestations of adverse reactions included hematologic injury in 12 patients (8.5%; grade 1 in 4 and grade 2 in 8 patients), hypertension in 11 patients (7.7%; grade 1 in 4, grade 2 in 3, grade 3 in 2, and grade 4 in 2 patients), skin injury in 8 patients (5.6%; grade 2 in 5 and grade 3 in 3 patients), bleeding events in 6 patients (4.2%; grade 1 in 3, grade 3 in 1, and grade 4 in 2 patients), gastrointestinal reaction in 6 patients (4.2%; grade 1 in 3 and grade 2 in 3 patients), proteinuria in 3 patients (2.1%, grade 1), pulmonary embolism in 1 patient (0.7%, grade 4), gastric perforation in 1 patient (0.7%, grade 4), and alopecia in 1 patient (0.7%, grade 1). Bev was not discontinued in 37 patients who developed grade 1-2 adverse events, and 25 of them were given symptomatic treatments. Patients with grade ≥3 adverse reactions stopped Bev and received symptomatic treatments. All patients recovered or were improved.Conclusions:The common adverse reactions in Bev treatment for NSCLC include hematologic injury, hypertension, skin injury, bleeding events, gastrointestinal reaction, and proteinuria, most of which are of grade 1-2 in severity. Severe adverse effects such as pulmonary embolism and gastric perforation occurred occasionally. Patients with grade ≥ 3 adverse reactions have a good prognosis when Bev is discontinued and symptomatic treatments are given.

Objective:To explore the occurrence and characteristics of adverse reactions related to bevacizumab (Bev) in treatment of non-small cell lung cancer (NSCLC).Methods:The medical records of NSCLC patients treated with Bev in the Respiratory Department of Bozhou Hospital of Traditional Chinese Medicine from May 2019 to March 2021 were collected. Patients with Bev-related adverse reactions, which were judged by Naranjo scoring method, were selected. The relevant information in these patients was extracted from their medical records, and the occurrence and outcomes of the adverse reactions (incidence, time of occurrence, clinical manifestation, severity, etc.) were analyzed retrospectively. The dosing regimen of Bev was IV infusion of 7.5 mg/kg once per 21 days (1 cycle).Results:A total of 142 patients were included in the analysis, and 17 (12.0%), 20 (14.1%), 51 (35.9%), 35 (24.6%), and 19 (13.4%) patients received 1, 2, 3, 4, and 5 cycles of Bev treatment, respectively. All patients were treated with combination regimen with traditional chemotherapy drugs, including pemetrexed in 10 patients (7.0%), pemetrexed+carboplatin in 41 patients (28.9%), and pemetrexed+cisplatin in 91 (64.1%) patients, respectively. Among the 142 patients, 49 (34.5%) had adverse reactions, which were classified as grade 1, 2, 3, and 4 in severity in 18, 19, 6, 6 patients respectively, and the incidence of serious adverse reactions (≥ grade 3) was 8.5% (12/142). The clinical manifestations of adverse reactions included hematologic injury in 12 patients (8.5%; grade 1 in 4 and grade 2 in 8 patients), hypertension in 11 patients (7.7%; grade 1 in 4, grade 2 in 3, grade 3 in 2, and grade 4 in 2 patients), skin injury in 8 patients (5.6%; grade 2 in 5 and grade 3 in 3 patients), bleeding events in 6 patients (4.2%; grade 1 in 3, grade 3 in 1, and grade 4 in 2 patients), gastrointestinal reaction in 6 patients (4.2%; grade 1 in 3 and grade 2 in 3 patients), proteinuria in 3 patients (2.1%, grade 1), pulmonary embolism in 1 patient (0.7%, grade 4), gastric perforation in 1 patient (0.7%, grade 4), and alopecia in 1 patient (0.7%, grade 1). Bev was not discontinued in 37 patients who developed grade 1-2 adverse events, and 25 of them were given symptomatic treatments. Patients with grade ≥3 adverse reactions stopped Bev and received symptomatic treatments. All patients recovered or were improved.Conclusions:The common adverse reactions in Bev treatment for NSCLC include hematologic injury, hypertension, skin injury, bleeding events, gastrointestinal reaction, and proteinuria, most of which are of grade 1-2 in severity. Severe adverse effects such as pulmonary embolism and gastric perforation occurred occasionally. Patients with grade ≥ 3 adverse reactions have a good prognosis when Bev is discontinued and symptomatic treatments are given.

Objective: To compare the visual quality after topography-guided customized femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and wavefront-optimized FS-LASIK treatment in myopic eyes. Methods: A non-randomized controlled clinical study was performed.Seventy-eight eyes of 39 myopic patients undergoing FS-LASIK in Beijing Tongren Hospital from October 2016 to February 2017 were enrolled in this study and divided into two groups according to each patient's opinion, with matched demography between the two groups.Topography-guided customized FS-LASIK was performed on 42 eyes of 21 myopia in the topography-guided group, and wavefront-optimized FS-LASIK was performed on 36 eyes of 18 patients in the wavefront-optimized group.Visual acuity, refractive error, higher order aberrations (HOAs) and contrast sensitivity(CS) were compared between the two groups before and 6 months after surgery.Written informed consent was obtained from each patient before the operation.This study protocol was approved by Ethic Committee of Beijing Tongren Hospital (No.TRECKY2014-026). Results: The postoperative uncorrected visual acuity (UCVA) levels were eaqual to or better than the preoperative best corrected visual acuity (BCVA) in 95.2% patients in the topography-guided group, and in 94.4% patients in the wavefront-optimized group 6 months after surgery, respectively.There were no significant differences in the spherical equivalent, sphere refraction and cylinder refraction between the two groups (all at P>0.05). The amount of induced coma was significantly lower in the topography-guided group than that in the wavefront-optimized group ([0.07±0.22]μm vs.[0.22±0.16]μm) at 6 mm pupil.LogCS improved under the 12.0 c/d in the background of mesopic in the topography-guided group and decreased under the 18.0 c/d both in the background of mesopic and mesopic + glare in the wavefront-optimized group 6 months after surgery, with signifcant differences between them (all at P<0.05). LogCS values under 6.0, 12.0 and 18.0 c/d in the background of mesopic and 18.0 c/d in the background of mesopic+ glare in the topography-guided group were significantly higher than those in the wavefront-optimized group 6 months after surgery, with significant differences between the two groups (all at P<0.05). Conclusions Topography-guided FS-LASIK has lower higher-order aberrations and better CS than wavefront-optimized FS-LASIK.