ObjectiveTo investigate the effects of three traditional Chinese medicine formulas for nourishing kidney Yin on the occurrence of breast cancer， including Zuoguiwan（ZGW）， Liuwei Dihuangwan（LWDHW） and Erzhiwan（EZW）， and to explore their preventive mechanisms from the phagocytic function of macrophages. MethodsTen-month-old post-breeding female mice were randomly divided into the blank group， soy isoflavone group（0.13 g·kg^-1·d^-1， mixed with feed）， ZGW group（2.34 g·kg^-1·d^-1）， LWDHW group（0.56 g·kg^-1·d^-1）， and EZW group（4.68 g·kg^-1·d^-1）. The mice were palpated every 3 d until the age of 18 months， and those with detected lumps were confirmed for tumor development through hematoxylin-eosin（HE） staining， and the incidence of breast cancer in mice was calculated. A total of 40 SPF-grade female SD rats were randomly divided into the blank serum group（physiological saline）， ZGW drug-containing serum group（16.20 g·kg^-1·d^-1of ZGW）， LWDHW drug-containing serum group（3.89 g·kg^-1·d^-1 of LWDHW） and EZW drug-containing serum group（32.40 g·kg^-1·d^-1 of EZW）， each group was orally administered 3 times a day for 5 consecutive days. On the 5^th day， blood was collected from the abdominal aorta 1 h after the last gavage to prepare drug-containing serum. The effect of drug-containing serum with different concentrations on the viability of RAW264.7 cells was assessed by cell counting kit-8（CCK-8）. Taking 20% of drug-containing serum concentration as the research object， its effect on the expression levels of major histocompatibility complex-Ⅱ（MHC-Ⅱ）， CD80 and CD86 on the surface of RAW264.7 cells was detected by immunofluorescence（IF）， the phagocytic function of RAW264.7 cells was examined by flow cytometry， and the levels of interleukin-6（IL-6） and nitric oxide（NO） in RAW264.7 cells in the conditioned medium（CM） co culture system of 4T1 cells were detected by enzyme-linked immunosorbent assay（ELISA） and Griess assay. ResultsAfter prophylactic administration， the tumor incidence rates in the soy isoflavone group（4%）， ZGW group（4%）， LWDHW group（4%）， and EZW group（6%） were lower than that in the blank group（8%）. Compared with the blank serum group， the drug-containing serum of the three nourishing kidney Yin formulas could enhance the expression levels of MHC-Ⅱ， CD80 and CD86 on the surface of RAW264.7 cells， enhance phagocytic ability towards tumor cells， and reduce the content of IL-6 and increase the level of NO（P<0.05， P<0.01）. ConclusionThe three nourishing kidney Yin formulas can reduce the incidence of tumor in mice， the mechanism may be related to activating RAW264.7 cells， increasing their phagocytosis to breast cancer cells， and regulating the secretion of IL-6 and NO.

ObjectiveTo retrospectively analyze the clinical efficacy of Xibining Ⅱ prescription in the treatment of knee osteoarthritis with cold-dampness blockage syndrome by oral medication and to explore the influencing factors of endpoint events. MethodA real-world retrospective cohort design was adopted， and medical records of knee osteoarthritis patients with cold-dampness blockage syndrome treated with oral medication from the orthopedics outpatient department of Jiangsu Province Hospital of Chinese Medicine were collected. All patients received conventional Western medicine treatment and were divided into non-exposure group （573 cases） and exposure group （427 cases） according to whether or not they received treatment with Xibining Ⅱ prescription. Descriptive analysis of the baseline data of the 1 000 screened cases was performed using IBM SPSS 27.0. According to the baseline data， 334 pairs were matched using the propensity score matching method， resulting in a total of 668 cases in both groups. The changes in visual analogous scale （VAS）， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） total score， Japanese Knee Osteoarthritis Measure （JKOM） score， and traditional Chinese medicine （TCM） syndrome score before treatment and at 2， 6， 12 weeks after treatment， as well as the incidence of adverse reactions， were compared between the two groups. A multivariate logistic regression analysis was conducted to analyze the influencing factors of endpoint events， with clinical cure judged based on the improvement rate of WOMAC total score before and after treatment. ResultAfter 12 weeks of treatment， compared to the results before treatment， the VAS， WOMAC total score， JKOM score， and TCM syndrome score of patients in both groups significantly decreased （P<0.01）. Compared to the non-exposure group， the exposure group showed a more significant reduction in VAS， WOMAC total score， JKOM score， and TCM syndrome score （P<0.01）. After 12 weeks of treatment， the clinical cure rate and significant efficiency were higher in the exposure group than in the non-exposure group （P<0.05）. Compared to the results before treatment within each group， VAS， WOMAC pain， stiffness， function scores， JKOM score， and TCM syndrome score significantly decreased at 2， 6， 12 weeks after treatment in both groups （P<0.01）. Compared to the non-exposure group at the same time points， the exposure group showed a reduction in VAS at 2， 12 weeks， WOMAC pain at 6， 12 weeks， and function scores at 12 weeks （P<0.05， P<0.01）. The JKOM score decreased at 6， 12 weeks， and the TCM syndrome score significantly decreased at 2， 6， 12 weeks in the exposure group （P<0.05， P<0.01）. Multivariate logistic regression analysis at 12 weeks showed that factors affecting clinical cure included the course of disease， history of alcohol consumption， hypertension， coronary heart disease， and the use of Xibining Ⅱ prescription （P<0.05， P<0.01）. Compared to the non-exposure group at the same time points， the incidence of epigastric discomfort in the exposure group was lower at 2， 12 weeks （P<0.01）， the incidence of diarrhea and vomiting was slightly higher than that in the non-exposure group， but the difference was not statistically significant. ConclusionThe clinical application of Xibining Ⅱ prescription combined with conventional Western medicine treatment in the treatment of knee osteoarthritis with cold-dampness blockage syndrome is more effective than conventional Western medicine treatment alone. It can significantly reduce VAS， WOMAC total score， JKOM score， and TCM syndrome score， with more pronounced long-term effects and a low incidence of adverse reactions.

Objective To investigate the role of solute carrier family 7 member 11(SLC7A11)in the pathogenesis and progression of clear cell renal cell carcinoma(ccRCC)and its prognostic significance.Methods Mendelian randomization analysis was employed to identify genes causally associated with the risk of ccRCC.The expression patterns and prognostic relevance of SLC7A11 were assessed using RNA sequencing data and clinical information obtained from the UCSC Xcna pan-cancer cohort.Gene set enrichment analysis(GSEA)was conducted using data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma(TCGA-KIRC)dataset(training set).A prognostic model based on SLC7A11 was then developed using stepwise Cox regression and validated externally in the E-MTAB-1980 cohort(validation set).Results Elevated level of SLC7A11 was associated with an increased risk of ccRCC(HR=1.27,95％CI:1.15-1.40,P＜0.001).SLC7A11 was overexpressed in various tumors and correlated with higher T stage and poorer survival(P＜0.05).GSEA demonstrated that SLC7A11 was enriched in pathways related to proliferation and metastasis,including E2F and epithelial-to-mesenchymal transition signaling pathways.Moreover,the SLC7A11 prognostic model exhibited robust predictive performance in both the training set(1-,3-,and 5-year AUC=0.78,0.73,0.71,respectively)and the external validation set(1-,3-,and 5-year AUC=0.70,0.71,0.72,respectively).Conclusion SLC7A11 can be a potential biomarker and therapeutic target for ccRCC,offering novel perspectives for precision medicine.

The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

Objective To explore the relationship and the clinical significance of homeobox gene B1 (HOXB1 )and microRNA-31 75 (miR-31 75)expressions in human glioma.Methods The expression levels of HOXB1 and miR-31 75 in 60 glioma tissues and 1 5 normal brain tissues were analyzed by real-time fluores-cent quantitative PCR (qRT-PCR).Spearman rank correlation analysis was performed to explore the relation-ship between HOXB1 and miR-31 75 in human glioma tissues.The relationship between HOXB1 (or miR-31 75)and clinical pathological characteristics of glioma patients was analyzed.The correlation of HOXB1 (or miR-31 75)and survival rate was calculated by Kaplan-Meier.And COX regression models were used to assess the prognostic factors.Results Compared with normal brain tissues,the expression of HOXB1 was significant-ly decreased in glioma tissues (1 .498 ±0.323 vs.0.946 ±0.588,t =-5.680,P =0.000);and the expre-ssion of miR-31 75 was obviously increased in glioma tissues (1 .008 ±0.355 vs.2.076 ±0.841 ,t =4.274, P =0.000),and HOXB1 expression was negatively correlated with miR-31 75 expression in glioma tissues (r =-0.601 ,P =0.000).HOXB1 expression was related with histologic grade (χ2 =4.848,P =0.028), and miR-31 75 expression was related with histologic grade (χ2 =5.640,P =0.01 8)and Karnofsky score (χ2 =4.785,P =0.029).The results of Kaplan-Meier revealed that there were significant differences in median survival time between HOXB1 (or miR-31 75)high-expression group and HOXB1 (or miR-31 75)low-expression group [HOXB1 :(21 .0 ±4.0)months vs.(7.0 ±0.8)months;χ2 =7.495,P =0.006;miR-31 75:(6.0 ±0.6)months vs.(1 6.0 ±5.8)months;χ2 =9.591 ,P =0.002].COX regression models showed that tumor degree (RR =6.556,95% CI:1 .1 96-35.952,P =0.002),HOXB1 (RR =0.01 8, 95%CI:0.001 -0.31 2,P =0.006)and miR-31 75 (RR =2.098,95%CI:1 .663-7.51 3,P =0.037)were independent prognostic factors for prognosis.Conclusion The HOXB1 expression may be negatively correlated with miR-31 75 in human glioma tissues,and the expression levels of HOXB1 and miR-31 75 are associated with the glioma malignant degree,survival time and prognosis of glioma patients.

Objective Parkinson's disease( PD) is a common chronic neurodegenerative disease,with four major symptoms of resting tremor, muscle rigidity, slow motion and postural balance disorder?The pathogenesis of Parkinson's disease is still unknown?A large number of studies suggested that may be the result of the interaction of genetic factors,environmental factors,aging,immune factors,specifically involved in oxidative stress,mitochondrial damage,and other mechanisms?There were 50% patients characterized by tremors,tremor is the most difficult symptoms to treat of PD, but the mechanism is still under controversial, so it ’ s of great significance to understand the generation of PD tremor, which helps to promote the clinical treatment and diagnosis.

Objective To study the role of call stimulate in arousal of coma patients after severe craniocerebral injury.Methods Twenty patients with severe craniocerebral trauma coma,admitted to our hospital from June 2014 to June 2015,were randomly divided into stimulation group (n=13) and control group (n=7).In addition to the regular relatives call stimulation,other treatments in stimulation group were the same as the control group.One,2,and 4 weeks after call stimulation,Glasgow Coma Scale (GCS) scores,blood flow velocity changes of internal carotid artery (ICA) and middle cerebral artery (MCA),and neurotransmitter contents of5-hydroxytryptamine (5-HT),dopamine (DA),norepinephrine (NE) and acetylcholine (Ach) in the cerebrospinal fluid (CSF) were detected.Results The consciousness was significantly improved in the stimulation group since the second week;at the 4th week,the GCS scores (11.85±2.58) were significantly higher than those in the control group (9.14±2.85,P＜0.05).ICA and MCA blood flow velocity of both groups reached peak level in the first week,and then,gradually decreased till the end of the observation;ICA velocity value in the stimulation group (72.85± 7.45) was lower than that in the control group (82.14±11.61).The DA,Ach and NE content in the stimulation group were significantly increased at the 4th week as compared with those in the control group (P＜0.05);but no significant difference was noted between the two groups in the content of 5-TH (P＞0.05).Conclusion The call stimulus has certain awaking effect on coma patients,whose mechanism may be related to call induced changes of cerebral blood flow velocity and related neurotransmitter release.

OBJECTIVETo investigate the role of P38 mitogen-activated protein kinase (P38 MAPK) signaling pathway in regulating the expression of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) in the substantia nigra (SN) of a mouse model of Parkinson's disease (PD).

METHODSC57BL/6N mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish an subacute PD model, and the behavioral changes of the mice were observed. Immunohistochemistry and Western blotting were employed to detect the expressions of tyrosine hydroxylase (TH), NF-κB, iNOS and phosphorylated P38 (p-P38) in the midbrain before and after treatment with SB203580.

RESULTSCompared with the control mice, the PD mouse models presented with typical symptoms of PD and showed significantly increased number of p-P38-, NF-κB-, and iNOS-positive cells in the SN area (P<0.01) with significantly reduced number of TH-positive neurons (P<0.01). After SB203580 treatment, the number of p-P38-, NF-κB-, and iNOS-positive cells was reduced obviously (P<0.01) and the number of TH-positive neurons in the SN increased significantly in the PD model mice (P<0.01).

CONCLUSIONP38 MAPK signaling pathway may play an important role in modulating NF-κB and iNOS expression in the SN in the early stage of MPTP-induced subacute PD, and SB203580 can inhibit P38 signaling pathway to protect the DA neurons in PD model mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Disease Models, Animal ; Imidazoles ; MAP Kinase Signaling System ; Mice ; Mice, Inbred C57BL ; metabolism ; NF-kappa B ; metabolism ; Neurons ; Nitric Oxide Synthase Type II ; metabolism ; Parkinson Disease ; metabolism ; Phosphorylation ; Pyridines ; Substantia Nigra ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To evaluate expression and significance of TLR4 and NF-κB on inflammatory injure after intracerebral hemorrhage in rats .Methods 60 Sprague Dawley maleness rats were randomly divided into Sham group ,12 h ,24 h ,72 h and 7 d af-ter ICH group(12 s) .The ICH was induced by injection of autologous blood in rats .The behavioral changes were detected by neu-rologic deficit score .The water content of the brain was used to evaluate brain edema changes .Number of TLR4 and NF-κB positive cells by Nissl staining and the expression of protein determined by immunohistochemistry and Western blot .Results After ICH 12 h ,expression of TLR4 and NF-κB positive cells around the hematoma were expressed ,with the extension of the time ,expression was gradually increasing ,and after ICH 72 h the expression of protein were the highest .Cerebral edema and severe neurological damage occurred .Western blot shows the amount of TLR4 expression and NF-κB were in line with the result .Conclusion After in-tracerebral hemorrhage in rat causing inflammatory injure of brain tissue around the hematoma .TLR4 may activate the expression of NF-κB involved in the secondary inflammatory injure after intracerebral hemorrhage in rats .