OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

BACKGROUND:Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level,and the mechanism of related signaling pathways is an important way to further understand osteoporosis.At present,traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis.Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action. OBJECTIVE:To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature. METHODS:"Kaempferol,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathways"were used as Chinese and English search terms to search CNKI,WanFang,VIP,PubMed,Web of Science and Embase databases for relevant literature published from database inception to February 2023. RESULTS AND CONCLUSION:Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation,proliferation and apoptosis of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts.Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways.Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex.Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis.Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification.Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway.Kaempferol inhibits the expression of ERK,JNK,p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway,thus protecting osteogenesis.Kaempferol enhances the expression of osteogenic factors,bone morphogenetic protein-2,p-Smad1/5/8,β-catenin and Runx2,inhibits the expression of Peroxisome proliferation-activated receptor,and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.

Objective To evaluate the benefits of subcutaneous continuous glucose monitoring(SCGM)in blood glucose control of ICU patients,in order to open up the new ideas for blood glucose management in ICU patients.Methods The databases of PubMed,Cochrane Library,Embase,Web of Science,Wanfang,VIP,CNKI and China biomedical literature service system(SinoMed)were retrieved for the relevant randomized controlled trials(RCT)on SCGM in ICU patients from the establishment of the database to April 2024.The two researchers independently screened the literatures,extracted the data,and evaluated the risk of bias of the included studies by using Cochrane risk assessment tools.The Review manager5.4 was used for conducting the meta-analysis and the Stata16.0 was used for conducting the publication bias and sensitivity analysis.Re-sults Eighteen literatures were included,of which the quality evaluation of 17 literatures were the medium and included in the final study,1 literature was evaluated as low quality and was excluded from the analysis.A total of 1 799 research subjects,including the patients admitted to ICU after tumor and cardiac surgery,sepsis,oral space infection,acute pancreatitis,craniocerebral injury,etc,among them the diabetic patients accounted for 8.5％.The test group(SCGM)and control group(capillary glucose measurement by bedside glucometer or arterial glucose measurement by blood gas analyzer)showed a statistically significant in the incidence of hy-poglycemia(RR=0.35,95％CI:0.25-0.47,P＜0.001),mean blood glucose(SMD=-0.13,95％CI:-0.25 to-0.00,P=0.040),and the time proportion of glucose in the target range(SMD=0.29,95％CI:0.10-0.49,P=0.003);the insulin dosage subgroup analysis results showed that the insulin dosage between the two groups in the intensive insulin treatment group had no statistically significant difference(SMD=-0.44,95％CI:-1.05 to 0.17,P=0.160),but the insulin dosage between the two groups in the non-inten-sive insulin treatment group had statistically significant difference(SMD=-2.01,95％CI:-2.29 to-1.72,P＜0.001).Conclusion Compared with capillary glucose measurements by the bedside glucose me-ters or arterial glucose measurements by blood gas analyzers,using SCGM in ICU patients could reduce the in-cidence rate of hypoglycemia,insulin dosage and mean blood glucose,and improve the time proportion of glu-cose in the target range.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) on learning and memory impairment in vascular dementia (VD) rats by observing the influences on the N-methyl-D-aspartate receptor (NMDAR)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and the excitotoxicity induced by hippocampal calcium overload. METHODS: Thirty-two male SD rats of SPF grade were selected and randomized into a normal group (6 rats), a sham-operation group (6 rats) and an operation group (20 rats). VD model was established with the modified Pulsinelli's four-vessel occlusion (4-VO) method. Twelve rats after successfully modeled were assigned randomly into a model group and an EA group, 6 rats in each one. In the EA group, EA was delivered at bilateral "Fengchi" (GB 20) and "Sishencong" (EX-HN 1), with the continuous wave, the frequency of 2 Hz and the electric current of 1 mA. Stimulation intensity was adjusted depending on the slightly trembling of rat head. EA was given once daily, 30 min each time; and EA intervention was delivered for 21 days continuously. Using Morris water maze test, the learning and memory function was assessed. The neuronal morphology in the hippocampal CA1 was observed with HE staining; the level of glutamate (GLU) in serum and hippocampal tissue, as well as the activity of calcium pump (Ca²⁺-ATP) in the hippocampus were detected using colorimetric method. The protein expression of NMDAR, calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ), phosphorylated cyclic phosphoradenosine effector element binding proteins (p-CREB), CREB, and BDNF in the hippocampal CA1 was detected using immunohistochemistry. The protein expression of NMDAR, CREB, p-CREB and BDNF in the hippocampal tissue was detected using Western blot method. RESULTS: Compared to the sham-operation group, in the model group, the escape latency was prolonged and the platform crossing times of rats were reduced (P<0.01), the hippocampal neuron structure was damaged to different degrees, the structure in hippocampal CA1 was loosened, the arrangement disorganized, with clear grid-like structure; the neuronal morphology was irregular, pyknosis and even dissolution occurred, glial cells increased, blood capillary was dilated and the inflammatory cells were infiltrated and scattered. The level of GLU in the serum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were reduced (P<0.01, P<0.05); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB were dropped (P<0.05). In comparison with the model group, in the EA group, the escape latency was shortened and the platform crossing times of rats rose (P<0.01), the arrangement was improved in the hippocampal CA1, the neuronal morphology was intact, the nucleoli were clear relatively and the pyknosis or dissolution were attenuated, the numbers of glial cells reduced relatively, the dilation of blood capillary was alleviated. The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were elevated (P<0.05, P<0.01); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB increased (P<0.05). CONCLUSION EA at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) can attenuate learning and memory impairment in VD rats, which may be obtained by reducing GLU level in hippocampal tissue, inhibiting hippocampal excitotoxicity, mediating protein expression related to the NMDAR/CREB/BDNF signaling pathway, and maintaining neuronal survival and growth.
Electroacupuncture ; Male ; Animals ; Rats, Sprague-Dawley ; Learning ; Memory ; Signal Transduction ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Memory Disorders/therapy* ; Brain-Derived Neurotrophic Factor/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Dementia, Vascular/therapy*

Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2-knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.

Objective:To investigate the relationship between serum vascular endothelial growth factor (VEGF), peripheral blood microRNA-126 (miR-126) and the number and distribution of cerebral microbleeds (CMBs).Methods:Consecutive patients with non-acute ischemic cerebrovascular disease admitted to the Department of Neurology, the First Affiliated Hospital of Baotou Medical College from June 2019 to June 2020 were enrolled. The clinical data were collected, 3.0 T MRI examination was performed, and susceptibility-weighted imaging was used to detect CMBs. The serum VEGF concentration was detected by enzyme-linked immunosorbent assay, and miR-126 was detected by fluorescence quantitative polymerase chain reaction. Multivariate logistic regression analysis was used to determine the independent influencing factors of CMBs. Multiple linear regression analysis was used to determine the correlation between serum VEGF concentration, miR-126 in peripheral blood and the number of CBMs. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum VEGF concentration and relative expression of miR-126 in peripheral blood for CMBs. Results:A total of 193 patients with non-acute ischemic cerebrovascular disease were enrolled, including 110 patients (57.0%) in the non-CMBs group, 20 (10.4%) in the strictly lobar CMBs group and 63 patients (32.6%) in non-strictly lobar CMBs group. The comparison among the three groups showed that age might be a risk factor for strictly lobar CMBs, while higher VEGF, higher cystatin C level, lower relative expression of miR-126 in peripheral blood, hypertension and previous stroke or transient ischemic attack might be the risk factors for non-strictly lobar CMBs. Multivariate logistic regression analysis showed that higher serum VEGF concentration was an independent risk factor for non-strictly lobar CMBs (odds ratio 1.186, 95% confidence interval 1.035-1.358; P=0.014), while the higher relative expression of miR-126 was an independent protective factor for non-strictly lobar CMBs (odds ratio 0.154, 95% confidence interval 0-0.269; P=0.026). Multiple linear regression analysis showed that higher serum VEGF concentration ( r=0.848, P<0.001) and the lower relative expression of miR-126 ( r=-0.043, P=0.035) significantly increased the number of CMBs. ROC curve analysis showed that the area under the curve of serum VEGF for predicting non-strictly lobar CMBs was 0.803 (95% confidence interval 0.741-0.865), the optimal cut-off value was 120.55 ng/L, the sensitivity was 70.7%, and the specificity was 75.5%. Conclusions:In patients with non-acute ischemic cerebrovascular disease, there is a significant correlation between serum VEGF concentration and the relative expression of miR-126 in peripheral blood and the number and distribution of CMBs. Serum VEGF can be used as a biomarker for predicting the presence of non-strictly lobar CMBs.

Long non-coding RNA (LncRNA) is a kind of RNA longer than 200nt, whose abnormal expression plays a significant role in the development of tumors. Metastasis-associated lung adenocarcinoma transcription 1 (MALAT1), as one of LncRNAs, is closely related to the pathogenesis of breast cancer. MALAT1 can affect the tumorigenesis and progression of breast cancer and is expected to be an effective target for the diagnosis and treatment of breast cancer. Herein, we review the research status of MALAT1 in breast cancer.

Objective To explore the effect of prognostic nutrition index (PNI) on the overall survival time of patients with brain metastases of lung adenocarcinoma.Methods A retrospective analysis was performed on the clinic data of 274 patients who were admitted to our hospital and confirmed with brain metastases of lung adenocarcinoma from May 2013 to May 2016.The prognosic factors for brain metastases such as PNI,gender,age,smoking history,epidermal growth factor receptor (EGFR) mutation status,Karnofsky performance status (KPS) score,the number of brain lesions,treatment of brain lesions,extracranial metastases and the status of primary disease were analyzed.The receiver operating characteristic (ROC) curve was drawn to determine the optimal cut-off value of PNI,and the patients were divided into high PNI group and low PNI group.The univariate and multivariate prognostic analyses were performed by the Log-rank test and the Cox proportional hazards model.Results The patients were divided into high PNI (＞ 50.45) group (n =72) and low PNI (≤50.45) group (n =202).The median overall survival (OS) was 11.20 months in all patients with brain metastases,and the median OS of the low PNI group and high PNI group were 10.13 months and 15.17 months respectively.The univariate analysis results showed that gender (x2 =5.459,P =0.019),age (x2 =3.986,P =0.046),smoking or not (x2 =6.878,P =0.009),EGFR mutation status (x2 =20.484,P＜0.001),KPS score (x2 =126.573,P ＜ 0.001),extracranial metastases or not (x2 =4.403,P =0.036),treatment on the brain lesions (x2 =40.444,P ＜ 0.001) and PNI (x2 =7.972,P =0.005) were related to the prognosis.The Cox multivariate analysis results showed that age (HR =1.580,95％ CI:1.104-2.295,P =0.012),EGFR mutation status (HR =0.549,95％ CI:0.408-0.738,P ＜ 0.001),KPS score (HR =0.077,95％CI:0.045-0.134,P ＜ 0.001),treatment on brain metastases (HR =0.882,95％ CI:0.789-0.987,P =0.029) and PNI (HR =0.614,95％ CI:0.437-0.861,P =0.005) were related to the prognosis.Conclusion PNI is an independent prognostic predictor of brain metastases in patients with lung adenocarcinoma,and the high-PNI is correlated to the long OS of patients with brain metastases of lung adenocarcinoma,which has certain clinical practical value.

Objective To investigate the correlation between cornexin37 (Cx37) CI019T polymorphism and ischemic stroke and its outcome.Methods Restriction fragment length polymorphism analysis was used to detect the distribution of Cx37 C1019T polymorphism in a ischemic stroke group and a control group.The modified Rankin scale (mRS) was used to evaluate the neurological outcome at 3 months after onset.Results A total of 235 patients in the control group,and 232 patients in the ischemic stroke goup were recruited.In the ischemic stroke group,210 had a good outcome (mRS ＜3) and 22 had a poor outcome (mRS≥ 3).The TT genotype (12.93％ vs.6.39％ ; x2 =10.087,P =0.006) and T allele (31.25％ vs.21.49％ ; x2 =11.466,P=0.001) frequency in the ischemic stroke group were significantly higher than those in the control group.Multivariatelogistic regression analysis showed that TT genotype (odds ratio [OR] 5.794; 95％ confidence interval [CI] 1.405-23.894; P =0.015) and T allele (OR 131.016,95％ CI 6.943 -2 472.477; P =0.001)signifkantly increased the risk of ischemic stroke.Univariate analysis showed that TT genotype (OR 0.650,95％ CI 0.144 - 2,934; P =0.575),CT genotype (OR 0.622,95％ CI 0.234 - 1.655; P =0.342),and CC genotype (OR 0.654,95％ CI 0.268 - 1.595; P =0.350) had no significant correlation with the outcome of ischemic stroke.Conclusions Cx37 1019TT genotype and T allele may increase the risk of ischemic stroke.T allele is one of genetic susceptibility factors for ischemic stroke; however,its gene polymorphism is not associated with the outcome of ischemic stroke at 3 months after onset.