Chronic kidney disease（CKD）has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities，such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002，researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine，destroyed the intestinal mucosal barrier，led to the translocation of toxins，activated the systemic oxidative stress response，further promoted the progress of CKD.This article reviewed the function of gut microbiota，intestine-gut kidney axis，and the application of microbial preparations in CKD.

Objective:To investigate the role and mechanism of dopamine receptor D2(DRD2)in the immune microenvironment of breast cancer. Methods:The xenograft model of breast cancer is established using female C57BL/6J mice and murine breast cancer EO771 cells.Mice with transplanted tumor were treated by intraperitoneal injection of the specific antagonist of DRD2,thioridazine,while PBS was injected intraperitoneally in the control group.siDRD2 targeting DRD2 gene was intratumorally injected to tumor-bearing mice[negative control siRNA(siNC)was injected to the control group].The percentage of Ki-67 positive cells and CD4+T lymphocytes in tumor tissue was examined by immunohistochemical analysis.The proportion of CD45+CD4+T lymphocytes,CD45+CD4+IFNγ+Th1 cells and CD45+CD4+IL-1 7+Th17 cells was detected by flow cytometry. Results:Compared with the control group,the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)in tumor tissue were decreased in the thioridazine-treated group.The proportion of CD45+immune cells(P＜0.05)and CD4+T lymphocytes(P＜0.001)in thioridazine-treated group was higher than that in the control group.The proportion of Th1 cells(CD45+CD4+IFNγ+)increased(P＜0.001)in thioridazine-treated group.There was no significant changes in the proportion of Th1 7 cells(CD45+CD4+IL-1 7+)(P＞0.05).Compared with the control group(siNC),the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)were decreased in siDRD2 group.The proportion of tumor infiltrating CD4+T lymphocytes(P＜0.001)and Th1 cells(P＜0.001)in the siDRD2 group was higher than that in the siNC group,whereas the change in the proportion of Th1 7 cells was not statistically significant(P＞0.05). Conclusion:Down-regulation of DRD2 could promote the differentiation of Th1 cells and inhibit the proliferation of breast cancer cells in a mouse breast cancer model.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.

Toll-like receptor 3 (TLR3), as an important pattern recognition receptor (PRR), dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases. Atherosclerosis is proved as an inflammatory disease, and inflammatory events involved in the entire process of initiation and deterioration. However, the contribution of TLR3 to atherosclerosis remains unclear. Herein, we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis. Besides, activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules. Conversely, silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation. Given the aberrance in TLR3 functions on atherosclerosis progression, we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy. Therefore, we developed the novel ellipticine derivative SMU-CX24, which specifically inhibited TLR3 (IC₅₀ = 18.87 ± 2.21 nmol/L). In vivo, atherosclerotic burden was alleviated in Western diet fed ApoE^-/- mice in response to SMU-CX24 treatment, accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion. Thus, for the first time, we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression, thereby proposing a new strategy and probe for atherosclerosis therapy.

Background: Metabolic diseases pose considerable burden on the healthcare system worldwide, indi-cating the significance of prevention and treatment. In constitution theory of traditional Chinese med-icine, phlegm-dampness constitution (PDC) is the common basis of metabolic diseases. In clinical practice, Huatan Qushi (HTQS) decoction targeting on PDC can effectively improve metabolic indicators. However, its underlying biochemical mechanism still remains unclear.Methods: Eight PDC participants received HTQS decoction for three months. Their blood was collected at baseline and 1 and 3 months after intervention started. Related biomedical indicators were detected. High-throughput sequencing and RT-qPCR were used for validation. Due to the missing data, repeated measures with missing values in mixed models were used. Results: After 3-month treatment, HDL-C level increased (P<.001) and FBG, FINS, and HbA1c all showed decreasing trend at different time points (all P < .05). After miRNA high-throughput sequencing, compared with the baseline, differential miRNAs at 1 and 3 months were screened, and target gene prediction and KEGG pathway enrichment analysis were performed. The results displayed that metabolic disease-related pathways mainly included pathways in cancer, PI3K-Akt signaling pathway, etc. Further, RT-qPCR showed that hsa-miR-1237-3p differed statistically (P =.008). Then we validated the target genes of hsa-miR-1237-3p in the"Pathways in Cancer"pathway including SDF1, AC, CRK, and HGF, also known as upstream target genes of PI3K/AKT pathway. The results showed that two indicators of CRK and HGF were in statistical significance (P=.045 and P=.036, respectively). Conclusion: PDC serves as a common basis for various metabolic diseases. Through adjusting PDC, HTQS decoction can improve biomedical indicators including blood glucose, HbA1c, insulin, and HDL-C. The target pathway is"Pathways in cancer". Specifically, HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237-3p, and probably exerts effects on their downstream PI3K/AKT pathway.

Objective To study the pharmacological function of the aconitine in treating adjuvant arthritis(AA).Methods Fifty rats were randomly divided into the control group, AA model group, methotrexate group(0.5 mg/kg), and aconitine groups of different dosages (25, 100μg/kg). Except the control group, each group was injection of intradermal Freund's complete adjuvant (0.1 ml) into right hindpaw of rats to establish adjuvant arthritis model. On the 10th day after model onset, the aconitine were administered by gavage with 25, 100μg/kg once daily, and the methotrexate group was administered with 0.5 mg/kg methotrexate twice per week, and all groups were treated for 19 days. After the last administration, the foot swelling was measured by toe volume meter, arthritis index was calculated by 5-grade scoring method, spleen and thymus index were calculated, and the pathological changes of right ankle joint were observed by HE staining.Results After the model establishment, compared with the model group, the degree of swelling of the ankle at 20 days (668.7 ± 144.5μl, 566.9 ± 179.3μl vs. 912.1 ± 200.5μl), 24 days (833.1 ± 144.0μl, 803.9 ± 213.4μlvs.1069.5 ± 164.6μl) and 28 days (736.4 ± 115.0μl, 835.7 ± 170.1μlvs. 1107.2 ± 215.8μl) in the aconitine groups significantly decreased (P<0.05 orP<0.01). After the model establishment, compared with the model group, arthritic index scores at 18 days (3.1 ± 0.7, 3.2 ± 0.4vs. 3.8 ± 0.6), 24 days (3.1 ± 0.5, 3.4 ± 0.5vs.3.9 ± 0.3), 28 days (2.7 ± 0.6, 3.2 ± 0.9 vs. 4.0 ± 0.0) in the aconitine groups significantly decreased (P<0.05). Compared with the model group, the spleen index (3.5 ± 0.4, 3.3 ± 0.4, 4.0 ± 0.6vs.4.9 ± 0.5) respectively in the low and high dose group of aconitine and methotrexate group (P<0.01).Conclusion Aconitine has a certain degree therapeutic effect on AA rats.

Objective To evaluate the efficacy and safety of a 755 nm picosecond Alexandrite la-ser with a diffractive lens array in the treatment of facial photoaged skin .Methods Twenty-six pa-tients with facial photoaging were recruited and received 3 treatments at 4-week intervals .Laser energy was applied over the entire face at a fixed spot size of 6 mm ,with a fluence of 0 .71 J/cm2 and 5Hz . Blinded clinical assessment was performed by 2 independent dermatologists on a 5-point global pho-toaging scale (GPS) .Patients were also questioned on the extent of improvement of rhytides ,skin tightening ,and complexion with a 4-point global aesthetic improvement scale (GAIS) and satisfaction . Adverse events were also evaluated .Results Twenty-six patients completed the treatment .Compared with the baseline ,there was a significant improvement in facial photoaged skin after 3 treatments ,and these positive outcomes were maintained up to the 3-month follow-up ,according to the GPS and GAIS scores .Moderate pain and transient erythema were observed as the two main discomforts associated with the treatment .Most patients were satisfied with the treatment .Conclusions This 755 nm pico-second Alexandrite laser with a diffractive lens array optic is effective in the treatment offacial pho -toaged skin ,and the therapy also seems safe and well tolerated .

Objective To investigate the effects of artesunate combined with arsenic trioxide (ATO) on the proliferation and apoptosis of NB4 cells.Methods The NB4 cells were treated with different concentrations of artesunate and arsenic trioxide respectively for 48 h.The cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method.The cells were divided into 4 groups:control group,artesunate group,arsenic trioxide group,and the combination of artesunate and arsenic trioxide group.The cell cycle and apoptosis were detected by flow cytometry (FCM).The protein expression levels of Bcl-2 and Bax were detected by Western blot.Results The MTT results showed that compared with the control group,the proliferation inhibition rates of 0.25,0.50,1.00,2.00,4.00 μmol/L artesunate group (19.26％ ± 3.59％,36.53％ ± 2.67％,61.32％ ± 2.50％,70.30％ ± 3.15％,86.92 ± 0.02％) significantly increased (P＜0.05);the proliferation inhibition rates of 1,2,4,8,16 μmol/L arsenic trioxide group (12.69％ ± 2.43％,64.26％ ± 2.02％,85.10％ ± 2.67％,92.06％ ± 2.21％,93.67％ ± 3.36％) significantly increased (P＜0.05);and the proliferation inhibition rate (40.17％ ± 5.49％ vs.32.23％ ± 3.52％) of combination of artesunate and arsenic trioxide group significantly higher than the arsenic trioxide group (P＜0.05).Compared with the arsenic trioxide group,the percentage of G0/G1 phase cells (74.20％ ± 1.43％ vs.66.14％ ± 1.78％),the apoptosis rate (58.00％ ± 2.41％ vs.34.57％ ± 1.22％),and the expression level of Bax protein (1.35 ± 0.09 vs.1.13 ± 0.09) in the combination of artesunate and arsenic trioxide group significantly increased (P＜0.05),the expression level of Bcl-2 protein (0.45 ± 0.09 vs.1.03 ± 0.10) in the combination of artesunate and arsenic trioxide group significantly decreased (P＜0.05).Conclusions Artesunate can significantly enhance the proliferation inhibition and apoptosis induced by arsenic trioxide on NB4 cells.The possible mechanism of proliferation inhibition and apoptosis of NB4 cells by artesunate combined with arsenic trioxide may be related to reduce the expression of anti-apoptotic protein Bcl-2 and increase the expression of apoptotic protein Bax.