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.

ObjectiveThe study aims to investigate the intervention effect of modified Xiangsha Liujunzitang （M-XSLJZ） on intestinal-derived lipopolysaccharide （LPS）-activated Kupffer cell inflammation in rats with hyperlipidemia spleen deficiency syndrome. MethodsSeventy male SD rats were randomly divided into seven groups （n=10）： blank control （CON）， high-fat diet without spleen deficiency （HFD）， high-fat diet with spleen deficiency （SD-HFD）， M-XSLJZ low-， medium-， and high-dose groups （XS-L， XS-M， XS-H）， and western medicine control （R）. Spleen deficiency was induced in SD-HFD， XS-L， XS-M， XS-H， and R groups via irregular diet combined with exhaustive swimming for 15 days. The CON group received a standard diet， while other groups were fed a high-fat diet for 10 weeks to establish the hyperlipidemia model. After successful modeling， rats were treated for 8 weeks： M-XSLJZ was administered at 3.51， 7.02， 14.04 g·kg^-1 in XS-L， XS-M， and XS-H groups， respectively. The R group received 9×10^-4 g·kg^-1 of a reference drug. D-xylose excretion rate was measured by the phloroglucinol method. Blood lipids were assessed using an automated biochemical analyzer. Hematoxylin-eosin （HE） staining was used to evaluate the pathological conditions of the liver， and oil red O staining was used to observe the lipid deposition in the liver. The levels of LPS， portal vein serum LPS， LPS-binding protein （LBP）， serum interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to evaluate CD86 expression and CD68/TLR4 co-localization in the liver. Protein levels of TLR4， MyD88， NF-κB p65， and p-NF-κB p65 in Kupffer cells were analyzed via Western blot automated protein analysis. Hepatic IL-6， TNF-α， and IL-1β mRNA and protein levels were measured using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the CON group， the SD-HFD group showed a decrease in D-xylose excretion （P<0.01）. TC， TG， HDL-C， and LDL-C increased （P<0.05， P<0.01）. A large number of hepatic lipid vacuoles and orange-red lipid droplet deposition appeared in the liver. Ileal LPS， portal LPS， and LBP increased （P<0.05， P<0.01）. The levels of serum IL-6， TNF-α， and IL-1β increased （P<0.01）. The expression of CD86 was upregulated （P<0.01）， and the co-expression of CD68 and TLR4 was enhanced. The protein levels of TLR4， MyD88， and p-p65 in Kupffer cells increased （P<0.01）. The mRNA and protein levels of IL-6， TNF-α， and IL-1β increased （P<0.05， P<0.01）. Compared with the HFD group， the SD-HFD group exhibited decreased D-xylose excretion （P<0.01）， higher HDL-C， LDL-C （P<0.05）， increased portal LBP and LPS （P<0.05）， increased serum IL-6 and TNF-α （P<0.01）， upregulated CD86 （P<0.01）， enhanced CD68/TLR4 co-expression， and higher TNF-α mRNA/protein （P<0.05）. Compared with the SD-HFD group， all M-XSLJZ treatment groups showed reduced TC， TG， and LDL-C （P<0.05， P<0.01）. XS-H and R groups displayed improved hepatic lipid deposition. XS-H and R groups had lower ileal LPS， portal LPS， and LBP levels （P<0.05， P<0.01）. All M-XSLJZ treatment groups exhibited reduced serum IL-6， IL-1β， and TNF-α （P<0.01）. The XS-H group showed downregulated CD86 （P<0.01） and weakened CD68/TLR4 co-expression. The XS-H group had reduced TLR4， MyD88， and p-NF-κB p65 in Kupffer cells （P<0.01）. XS-H and R groups showed lower IL-6， TNF-α， and IL-1β mRNA/protein （P<0.05， P<0.01）. ConclusionM-XSLJZ may exert its lipid-lowering effects by inhibiting intestinal-derived LPS and alleviating Kupffer cell inflammation in the liver.

Objective To evaluate the efficacy of transfrontal neuroendoscopic surgery in the treatment of chronic subdural hematoma.Methods Analysis of clinical data of 80 cases of chronic subdural hematoma.According to the surgical method,40 cases were divided into traditional external drainage of parietaltuber,40 cases were divided into transfrontal neuroendoscopic small bone window hematoma removal.The treatment efficiency,hematoma recurrence rate,operation time and intraoperative blood loss were compared between the two groups.Results Treatment efficiency of neuroendoscopic group was 95.0%,significantly higher than drainage group 75.0%,hematoma recurrence rate one month after surgery of neuroendoscopic group was 5.0%,significantly lower than that in drainage group 25.0%,operation time of neuroendoscopic group was(54.1±7.5)min,longer than that of drainage group(40.7±9.4)min,the differences were statistically significant(P<0.05).The intraoperative blood loss of neuroendoscopic group was(30.1±4.5)mL,compared with(27.1±6.4)mL in the drainage group,the difference was not statistically significant(P>0.05).Conclusion Transfrontal neuroendoscopic surgery can significantly improve the efficacy of chronic subdural hematoma,and hematoma recurrence rate is extremely low.It is worthy of clinical application.

Inguinal hernia (IH) is a common complication in prostate cancer patients undergoing radical prostatectomy (RP), which seriously affects their quality of life.The repair of IH is often challenging due to the adhesion in the inguinal area caused by previous surgery.This article focuses on the risk factors for IH after RP, including surgical approach, postoperative anatomical changes, low body mass index (BMI), muscle loss, advanced age, international prostate symptom score (IPSS), and patent sheath process, and prevention strategies for IH after RP, including robot assisted laparoscopic radical prostatectomy (RARP) with IH repair, preservation of the posterior pubic space in RARP, treatment of the spermatic cord, extraperitoneal RARP, and intraoperative management of the sheath like process, aiming to provide reference for urologists and to improve patients' quality of life.

Objective:To investigate the changes and clinical significance of vascular endothelial growth factor (VEGF) and vascular cell adhesion molecule-1 (VCAM-1) levels in patients undergoing breast cancer resection before and after radiotherapy.Methods:A total of 110 patients who were treated in our hospital from Jun. 2022 to Jun. 2023 for breast cancer and were to receive radiotherapy after surgery were prospectively selected as the observation group. Another 110 healthy volunteers were selected as the control group. The levels of VEGF and VCAM-1 in peripheral blood were compared, and the relationship among general data, tumor pathology and peripheral blood VEGF and VCAM-1 in the observation group was analyzed, and their relationship with disease and prognosis was analyzed.Results:VEGF and VCAM-1 levels in peripheral blood in the observation group were significantly higher ( F=1288.37, 309.32, P<0.05). The levels of VEGF and VCAM-1 in peripheral blood in the observation group were significantly lower than before radiotherapy ( t=23.45, 11.88, P<0.05). Before and after radiotherapy, VEGF and VCAM-1 levels in peripheral blood in the observation group were correlated with tumor stage, tumor differentiation degree and Ki-67 proliferation index ( ttumor stage=7.05, 2.14, 4.52, 4.76, ttumor differentiation degree=7.12, 6.62, 2.81, 3.15, tKi67 proliferation index=7.25, 4.60, 4.24, 2.48, P<0.05) ; Of 110 patients in the observation group, 73 were effective and 34 were ineffective. VEGF and VCAM-1 in effective group were significantly lower ( t=7.27, 9.08, P<0.05). Spearman correlation coefficient analysis showed that VEGF and VCAM-1 levels were significantly positively correlated with tumor stage and Ki67 proliferation index before and after radiotherapy ( rbefore radiotherapy=0.64, 0.54, 0.52, 0.52, rafter radiotherapy=0.32, 0.39, 0.37, 0.24, P<0.05), and negatively correlated with tumor differentiation degree ( rbefore radiotherapy=-0.41, -0.31, rafter radiotherapy=-0.68, -0.41, P<0.05). The prognostic value of combined radiotherapy was 0.801 [95% CI (0.714-0.871) ], which was higher than that of VEGF and VCAM-1 alone 0.690 [95% CI (0.5955-0.775) ] and 0.734 [95% CI (0.641-0.814) ]. Conclusion:The changes of VEGF and VCAM-1 levels in peripheral blood have a certain value in evaluating the short-term prognosis of patients undergoing breast cancer resection by radiotherapy.

Objective:To observe the effect of pecking moxibustion on the pattern characteristics of redness,swelling,heat,and pain in the affected joints,also the synovial cell ultrastructure in rats with rheumatoid arthritis(RA)due to damp heat affecting bones/joints,and to explore the anti-inflammatory mechanism of pecking moxibustion in treating the early stage of RA. Methods:Eighteen rats were randomly selected from 78 female ones as the blank group,and all the other rats were subjected to preparing the"differentiation of disease and pattern"RA model due to damp heat affecting bones/joints by using the method of"collagen-induced arthritis plus windy,damp,and hot environment stimulation".Fifty-four rats with successful modeling were randomly divided into a model group,a drug group,and a pecking moxibustion group,with 18 rats in each group.Rats in the drug group were given methotrexate at a dose of 1 mg/(kg·bw)on the 1st,8th,and 15th days.Rats in the pecking moxibustion group were treated with pecking moxibustion at Quchi(LI11),Dazhui(GV14),and Ashi points,and each point was treated with moxibustion for 15 min every day and a total of 3 courses of treatment,with 6 d as a course of treatment.After treatment,the capillary permeability,joint swelling,joint surface temperature,and plantar thermal pain threshold of the diseased joints in rats were observed,and the ultrastructural changes of synovial cells were observed by transmission electron microscopy. Results:The local swelling,surface temperature,and Evans blue(EB)leakage volume were significantly higher(P<0.05),the thermal pain threshold was significantly lower(P<0.05),and the synovial cell ultrastructure was obviously damaged in the affected joints in the model group compared with the blank group.The swelling degree,surface temperature,and EB leakage volume were significantly reduced(P<0.05),the thermal pain threshold was significantly increased(P<0.05),and the ultrastructural abnormalities of synovial cells were significantly improved in the diseased joints in the drug group and the pecking moxibustion group compared with the model group.The thermal pain threshold of rats in the pecking moxibustion group was significantly improved compared with the drug group(P<0.05). Conclusion:Pecking moxibustion obviously improves the pattern characteristics of local redness,swelling,heat,and pain in the diseased joints of rats with RA due to damp heat affecting bones/joints and effectively repairs the ultrastructure of the damaged synovium.It suggests that the pecking moxibustion intervention has a significant anti-inflammatory effect on early RA.

Humans ; Myelin Sheath ; Astrocytes ; Phagocytosis ; Macrophages ; Ischemia

Objective:To explore the effects of conflicting stimuli generated by different chromatic lights on visual display terminal (VDT) on accommodative response and microfluctuation of myopes and emmetropes, and to investigate the possible relationship between chromatic light, accommodation and the development and progression of myopia.Methods:A non-randomized controlled trial was conducted.Forty-one subjects aged 22 to 30 years old were enrolled, including 19 emmetropes in emmetropic group and 22 myopes in myopic group.The subjects had the normal color vision and no ocular organic diseases.The interventions were screens of different colors.There were 7 chromatic light conditions, including 3 monochromatic lights (red, green, blue), 3 bichromatic lights (red+ green, red+ blue, green+ blue) and 1 polychromatic light (white=red+ green+ blue). Subjects were asked to look at a black E target on a VDT at a distance of 33 cm for more than 20 seconds.The background color of the VDT was changed randomly in the 7 chromatic light conditions.The accommodative responses were recorded with the Grand Seiko WAM-5500 automatic infrared refractor every 0.2 seconds and the accommodative microfluctuation was calculated as the standard deviation of the accommodative response.Accommodative response and accommodative microfluctuation under different chromatic light conditions were compared.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (No.2019-1564). Written informed consent was obtained from each subject.Results:No statistically significant difference was found in the accommodative response between the two groups ( Fgroup=2.626, P=0.113). There was a statistically significant difference under different chromatic light conditions between the two groups ( Flight=39.070, P<0.01). There were similar trends in the effects of various color lights in both groups, with the largest accommodative response under monochromatic red light, followed by the bichromatic light containing red light, and then the smallest accommodative response under monochromatic blue light, and the differences were statistically significant (all at P<0.05). The accommodative microfluctuations under red, green, blue, red+ blue, red+ green, blue+ green and white light conditions were (0.142±0.033), (0.128±0.038), (0.131±0.043), (0.139±0.039), (0.127±0.034), (0.131±0.043) and (0.139±0.042)D in emmetropic group, and (0.178±0.043), (0.164±0.043), (0.159±0.039), (0.174±0.042), (0.166±0.036), (0.159±0.031) and (0.174±0.035)D in myopic group, respectively, showing statistically significant differences between them ( Fgroup=12.146, P<0.01; Flight=2.782, P<0.05). The accommodative microfluctuations under the 7 light conditions were higher in myopic group than in emmetropic group, and the differences were statistically significant (all at P<0.05). In myopes, the accommodative microfluctuation was the largest under red light, which was significantly larger than that under blue light, and was the smallest under blue+ green light (all at P<0.05). There was no significant difference in the accommodative microfluctuation between bichromatic light and its two monochromatic lights, or between the polychromatic light (white light) and its three monochromatic lights (all at P>0.05). There was no significant effect of various chromatic lights on the accommodative microfluctuation in emmetropic group (all at P>0.05). Conclusions:The accommodative microfluctuation is greater in myopes than in emmetropes.The stimuli produced by long-wavelength light cause larger accommodative microfluctuation, while conflicting stimuli generated by different chromatic lights do not increase accommodative microfluctuation.

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.

Objective This study used high-throughput sequencing technology to detect the regulation of JianPiHuaTan Prescription(JPHT)on the ApoE-/-mouse miRNA related to vascular smooth muscle cells proliferation and migration,verify the expression of related proteins,and explore the therapeutic effect of JPHT on atherosclerosis.Methods Ten of C57BL/6J mice were used as control group,and 30 ApoE-/-mice were randomly divided into model group,western medicine group and JPHT group.Sequencing technology was performed on aortic sample to select the differentially expressed miRNA.We screened out the tagetted miRNA related to VSMCs proliferation and migration.RT-qPCR and Western blot technology were used to test the differentially expressed miRNA and tagetted protein.Results Compared with model group,a total of 9 miRNAs were changed in JPHT group,among which 7 were up-regulated and 2 were down-regulated.The expression of miRNA-34a was up-regulated in JPHT group.The miRNA-34a and α-SMA protein expression in aorta of JPHT group were significantly different with model group by RT-qPCR and Western blot experiment(P<0.01).Conclusion Jianpi Huatan Prescription may improve ApoE-/-mice atherosclerosis through inhibitting the proliferation of vascular smooth muscle cells by regulating miRNA-34a.