Effects of pressing moxibustion at Baihui (GV 20) and Guanyuan (CV 4) on cognitive impairment and serum levels of Aß1-42, tau, P-tau in patients with mild to moderate Alzheimer's disease. / åŽ‹ç¸ç™¾ä¼šã€å ³å ƒå¯¹è½»ä¸­åº¦é˜¿å°”èŒ¨æµ·é»˜ç— æ‚£è€ è®¤çŸ¥éšœç¢åŠè¡€æ¸ Aß1-42、tau、P-tau水平的影响.

OBJECTIVES: To compare the effects of pressing moxibustion at Baihui (GV 20) and Guanyuan (CV 4) combined with donepezil hydrochloride tablets and donepezil hydrochloride tablets alone on cognitive impairment in patients with mild to moderate Alzheimer's disease(AD), and to explore the mechanism of pressing moxibustion in the treatment of mild to moderate AD from the serum levels of ß-amyloid 1-42 (Aß1-42), microtubule-associated protein tau and phosphorylated tau (P-tau). METHODS: A total of 76 patients with mild to moderate AD were randomly divided into an observation group (38 cases, 4 cases dropped out) and a control group (38 cases, 2 cases dropped out). Patients in the control group were given oral donepezil hydrochloride tablets (5 mg each time, once a day). On the basis of the control group, patients in the observation group were treated with pressing moxibustion at Baihui (GV 20) and Guanyuan (CV 4), 5 cones per acupoint, once every other day, three times a week. Both groups were treated for 8 weeks. The scores of mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were compared between the two groups before treatment, after treatment and after 4 and 12 weeks of treatment completion. The serum levels of Aß1-42, tau and P-tau were detected before and after treatment in the two groups, and the safety was evaluated. RESULTS: At each time point after treatment, the MMSE and MoCA scores of the two groups were higher than those before treatment (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). After treatment, the serum levels of Aß1-42, tau and P-tau in the two groups were lower than those before treatment (P<0.05), and above indexes in the observation group were lower than those in the control group (P<0.05). There was no significant difference in the safety level between the two groups (P>0.05). CONCLUSIONS: The short-term and long-term effect of pressing moxibustion at Baihui (GV 20) and Guanyuan (CV 4) combined with donepezil hydrochloride tablets in improving cognitive impairment in mild to moderate AD is better than that of donepezil hydrochloride tablets alone, and can reduce serum levels of Aß1-42, tau and P-tau, which may be one of the mechanisms of pressing moxibustion to improve cognitive impairment.

Long-term effects of vegetation restoration and forest management on carbon pools and nutrient storages in northeastern Loess Plateau, China.

It is crucial for understanding the variations of carbon and nutrient pools within the ecosystems during long-term vegetation restoration to accurately assess the effects of different ecological restoration patterns. However, the long-term spatio-temporal variations of carbon and nutrient pools under different vegetation types remain unclear. The sites for long-term natural and planted forests (i.e., Natural secondary forest, Pinus tabulaeformis planted forest, Platycladus orientalis planted forest, and Robinia pseudoacacia planted forest) on the northeastern Loess Plateau, China were selected, to measure and analyze the differences and interannual variations of vegetation attributes at four synusiae and soil properties at 0-100 cm over the period of 12 years (2006-2017). The principal component analysis (PCA) and Mantel test were also conducted to explore the relationships among vegetation attributes, soil properties, and carbon and nutrient pools. The results showed that: compared with the planted forests, the natural secondary forest had lower arborous biomass (84.21 ± 1.53 t hm-2) and higher understory biomass and plant heights. Compared to planted forests, the secondary forest had higher soil carbon and nitrogen contents (13.74 ± 3.50 g kg-1 and 1.16 ± 0.34 g kg-1). The soil carbon pool in the secondary forest was 22.0% higher than planted forests, while the vegetation carbon pool in the P. tabulaeformis was 75.5% higher than other forests. Principal component analysis (PCA) and Mantel test revealed that vegetation attributes and soil properties had significant correlations with carbon and nutrient pools, especially at the arborous synusia (p < 0.01). The findings indicated that in the ecologically fragile Loess Plateau region, the selection of appropriate vegetation restoration types should be guided by varying ecological restoration goals and benefits, aiming to expected ecological outcomes. This insight offers a strategic implication for forest management that is tailored to improve carbon and nutrient pools in areas with similar environmental conditions.

Modulating the Coordination Environment of Carbon-Dot-Supported Fe Single-Atom Nanozymes for Enhanced Tumor Therapy.

Herein, carbon dot (CD)-supported Fe single-atom nanozymes with high content of pyrrolic N and ultrasmall size (ph-CDs-Fe SAzyme) are fabricated by a phenanthroline-mediated ligand-assisted strategy. Compared with phenanthroline-free nanozymes (CDs-Fe SAzyme), ph-CDs-Fe SAzyme exhibit higher peroxidase (POD)-like activity due to their structure similar to that of ferriporphyrin in natural POD. Aberration-corrected high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and X-ray absorption fine structure spectroscopy (XAFS) analyses show that metal Fe is dispersed in ph-CDs-Fe SAzyme as single atoms. Steady-state kinetic studies show that the maximum velocity (Vmax ) and turnover number (kcat ) of H2 O2  homolytic cleavage catalyzed by ph-CDs-Fe SAzyme are 3.0 and 6.2 more than those of the reaction catalyzed by CDs-Fe SAzyme. Density functional theory (DFT) calculations show that the energy barrier of the reaction catalyzed by ph-CDs-Fe SAzyme is lower than that catalyzed by CDs-Fe SAzyme. Antitumor efficacy experiments show that ph-CDs-Fe SAzyme can efficiently inhibit the growth of tumor cells both in vitro and in vivo by synergistic chemodynamic and photothermal effects. Here a new paradigm is provided for the development of efficient antitumor therapeutic approaches based on SAzyme with POD-like activity.

Multi-walled carbon nanotubes reversing the bone formation of bone marrow stromal cells by activating M2 macrophage polarization.

Multi-walled carbon nanotubes (MWCNTs) are an excellent bone tissue repair material both in vitro and in vivo. The interactions between MWCNTs and single type of cells of bone tissue, including osteoblasts, bone marrow stromal cells (BMSCs) or osteoclasts, have been extensively studied. However, the interactions between MWCNTs with different types of cells in the bone microenvironment remain elusive. Bone microenvironment is a complex system composed of different types of cells, which have interactions between each other. In this work, the effects of MWCNTs on bone microenvironment were firstly studied by culture of MWCNTs with BMSCs, osteoblasts, osteoclasts, macrophages and vascular endothelial cells, respectively. Then, co-culture systems of macrophages-BMSCs, macrophages-calvaria and macrophages-BMSCs-vascular endothelial cells were treated with MWCNTs, respectively. The osteogenic differentiation of BMSCs and osteoblasts was inhibited when these two types of cells were cultured with MWCNTs, respectively. Strikingly, when co-culture MWCNTs with BMSCs and macrophages, the osteogenesis of BMSCs was promoted by inducing the M2 polymerization of macrophages. Meanwhile, MWCNTs promoted the bone formation in the osteolysis model of calvaria ex vivo. In addition, the formation of osteoclasts was inhibited, and angiogenesis was increased when treated with MWCNTs. This study revealed the inconsistent effects of MWCNTs on single type of bone cells and on the bone microenvironment. The results provided basic research data for the application of MWCNTs in bone tissue repair.

A necroptosis-related prognostic model for predicting prognosis, immune landscape, and drug sensitivity in hepatocellular carcinoma based on single-cell sequencing analysis and weighted co-expression network.

Background: Hepatocellular carcinoma (HCC) is a highly lethal cancer and is the second leading cause of cancer-related deaths worldwide. Unlike apoptosis, necroptosis (NCPS) triggers an immune response by releasing damage-related molecular factors. However, the clinical prognostic features of necroptosis-associated genes in HCC are still not fully explored. Methods: We analyzed the single-cell datasets GSE125449 and GSE151530 from the GEO database and performed weighted co-expression network analysis on the TCGA data to identify the necroptosis genes. A prognostic model was built using COX and Lasso regression. In addition, we performed an analysis of survival, immunity microenvironment, and mutation. Furthermore, the hub genes and pathways associated with HCC were localized within the single-cell atlas. Results: Patients with HCC in the TCGA and ICGC cohorts were classified using a necroptosis-related model with significant differences in survival times between high- and low-NCPS groups (p < 0.05). High-NCPS patients expressed more immune checkpoint-related genes, suggesting immunotherapy and some chemotherapies might prove beneficial to them. In addition, a single-cell sequencing approach was conducted to investigate the expression of hub genes and associated signaling pathways in different cell types. Conclusion: Through the analysis of single-cell and bulk multi-omics sequencing data, we constructed a prognostic model related to necroptosis and explored the relationship between high- and low-NCPS groups and immune cell infiltration in HCC. This provides a new reference for further understanding the role of necroptosis in HCC.

Identification of the KCNQ1OT1/ miR-378a-3p/ RBMS1 Axis as a Novel Prognostic Biomarker Associated With Immune Cell Infiltration in Gastric Cancer.

Background: Gastric cancer (GC) is the second leading cause of cancer-related mortality and the fifth most common cancer worldwide. However, the underlying mechanisms of competitive endogenous RNAs (ceRNAs) in GC are unclear. This study aimed to construct a ceRNA regulation network in correlation with prognosis and explore a prognostic model associated with GC. Methods: In this study, 1,040 cases of GC were obtained from TCGA and GEO datasets. To identify potential prognostic signature associated with GC, Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression were employed. The prognostic value of the signature was validated in the GEO84437 training set, GEO84437 test set, GEO15459 set, and TCGA-STAD. Based on the public databases, TargetScan and starBase, an mRNA-miRNA-lncRNA regulatory network was constructed, and hub genes were identified using the CytoHubba plugin. Furthermore, the clinical outcomes, immune cell infiltration, genetic variants, methylation, and somatic copy number alteration (sCNA) associated with the ceRNA network were derived using bioinformatics methods. Results: A total of 234 prognostic genes were identified. GO and GSEA revealed that the biological pathways and modules related to immune response and fibroblasts were considerably enriched in GC. A nomogram was generated to provide accurate prognostic outcomes and individualized risk estimates, which were validated in the training, test dataset, and two independent validation datasets. Thereafter, an mRNA-miRNA-lncRNA regulatory network containing 4 mRNAs, 22 miRNAs, 201 lncRNAs was constructed. The KCNQ1OT1/hsa-miR-378a-3p/RBMS1 ceRNA network associated with the prognosis was obtained by hub gene analysis and correlation analysis. Importantly, we found that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may play a vital role in the diagnosis and prognosis of GC patients based on Cox regression analyses. Furthermore, our findings demonstrated that mutations and sCNA of the KCNQ1OT1/miR-378a-3p/RBMS1 axis were associated with increased immune infiltration, while the abnormal upregulation of the axis was primarily a result of hypomethylation. Conclusion: Our findings suggest that the KCNQ1OT1/miR-378a-3p/RBMS1 axis may be a potential prognostic biomarker and therapeutic target for GC. Moreover, such findings provide insights into the molecular mechanisms of GC pathogenesis.

Near-infrared-II photothermal ultra-small carbon dots promoting anticancer efficiency by enhancing tumor penetration.

Because of the particular environment of the tumor microenvironment, improving the deep penetration of drugs in tumor sites is a critical problem to improve the therapeutic effect of the tumor. The ultra-small nanoparticles can achieve deep tumor tissue penetration without modification, which shows tremendous significance in tumor therapy. In this work, the ultra-small permeable carbon dots (PCD) have been developed with near-infrared-II (NIR-II) window photothermal irradiation and good biocompatibility. These PCD showed multi-color fluorescence under visible light and photoacoustic signals under an excitation of 808 nm, guiding fluorescence and photoacoustic imaging for location and distribution in vitro and vivo. The PCD could penetrate the deep tissue in tumor spheroids and tissues. Meanwhile, the irradiated depth of the NIR-II window can provide sufficient photothermal energy with the deep penetration of PCD in tumor tissue to cause tumor ablation. Therefore, this PCD can be used as a safe, fluorescent, and photoacoustic imaging agent for guided NIR-II photothermal tumor therapy, which provides a new direction for the use of ultra-small carbon dots in anticancer therapy in the future.

[Abdominal acupoint thread embedding therapy based on "brain-intestinal connection" for mild-to-moderate Alzheimer's disease and its effects on serum levels of APP and Aß1-42].

OBJECTIVE: To compare the clinical efficacy of abdominal acupoint thread embedding therapy based on "brain-intestinal connection" combined with donepezil hydrochloride tablets and oral donepezil hydrochloride tablets alone for mild-to-moderate Alzheimer's disease (AD) and observe its effects on amyloid precursor protein (APP) and ß-amyloid protein1-42 (Aß1-42). METHODS: Sixty patients with AD were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 3 cases dropped off). The patients in the control group were treated with donepezil hydrochloride tablets (5 mg per day); based on the treatment in the control group, the patients in the observation group were treated with abdominal acupoint thread embedding therapy at Zhongwan (CV 12), Xiawan (CV 10), Huaroumen (ST 24), Wailing (ST 26), Daheng (SP 15), etc., once every 10 days. Both groups were treated for 2 months. The mini-mental state examination (MMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), activity of daily living scale (ADL), neuropsychiatric inventory questionnaire (NPI) as well as the serum levels of APP and Aß1-42 were observed before and after treatment in the two groups. RESULTS: After treatment, the MMSE scores in the two groups were higher than those before treatment (P<0.05), and the ADAS-Cog, ADL and NPI scores were lower than those before treatment (P<0.05). After treatment, the MMSE score in the observation group was higher than that in the control group (P<0.05), and the ADAS-Cog, ADL and NPI scores were lower than those in the control group (P<0.05). After treatment, the serum levels of APP and Aß1-42 were lower than those before treatment (P<0.05), and the serum levels of APP and Aß1-42 in the observation group was lower than those in the control group (P<0.05). CONCLUSION: The abdominal acupoint thread embedding therapy based on the theory of "brain-intestinal connection" combined with donepezil hydrochloride tablets can improve cognitive function, self-care ability of daily life and mental behavior, and reduce the serum levels of APP and Aß1-42 in patients with mild-to-moderate AD, which have superior clinical effect to donepezil hydrochloride tablets alone.

Resveratrol and Angiogenin-2 Combined With PEGDA/TCS Hydrogel for the Targeted Therapy of Hypoxic Bone Defects via Activation of the Autophagy Pathway.

The guarantee of cell survival under hypoxic conditions and rapid vascularization is a key in tissue engineering strategies for treating bone defects. Our study aimed to establish the protective role of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) in hypoxic conditions and realize rapid vascularization in bone defects. Resveratrol (Res), a non-flavonoid polyphenolic compound, and angiopoietin-2 (ANG2), a vascular activating factor, were applied to enhance BMSC and HUVEC survival, osteogenesis, and angiogenesis. The morphology, autophagy, viability, apoptosis, cycle, and osteogenic differentiation of BMSCs treated with Res were analyzed. The results indicated that Res could improve BMSC survival and differentiation via the autophagy pathway under hypoxic conditions. In addition, Res maintained HUVEC growth and proliferation in a hypoxic and ANG2 double-adverse environment via the autophagy pathway. To simulate a relatively hypoxic environment, small-aperture PEGDA/TCS hydrogels containing Res and ANG2 were prepared. BMSCs were cultured in the PEGDA/TCS scaffold and transplanted into a large tibial defect. CD31 immunofluorescence showed that the density and size of new blood vessels in the bone defect were significantly enhanced by ANG2 and Res at 8 weeks after surgery. H&E, Masson, and immunohistochemical staining results indicated that ANG2 combined with Res could promote new bone formation in defects. All these results suggested that Res combined with ANG2 may be a novel strategy for the targeted therapy of hypoxic bone defects with tissue engineering scaffolds.

The influence of dehydroepiandrosterone (DHEA) on fasting plasma glucose, insulin levels and insulin resistance (HOMA-IR) index: A systematic review and dose response meta-analysis of randomized controlled trials.

AIMS: The effect of DHEA supplementation on fasting plasma glucose (FPG), insulin levels (IN) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index in humans has not been assessed so far. Thus, we aimed to conduct a systematic review and meta-analysis of the randomized controlled trials (RCT) which assessed the effects of DHEA supplementation on FPG, IN and the HOMA-IR index in humans. METHODS: An extensive search was performed in Scopus, PubMed/MEDLINE, and Web of Science from inception to June 2020. Data was combined using the random effects model. RESULTS: 14 publications were included in this study. Overall results demonstrated that FPG was significantly altered after DHEA consumption (WMD: -2.185 mg/dl, P = 0.029). DHEA administration did not result in any significant changes in IN (WMD: 0.057 µU/mL, P = 0.067), and the HOMA - IR index (WMD: 0.174, P = 0.060). In the subgroup analyses, FPG significantly decreased in the subgroup who received DHEA supplementation in dosages of ≤50 mg/day (WMD: -2.29 mg/dl), when the treatment duration was <12 weeks (WMD: -5.25 mg/dl), and in subjects aged ≥60 years (WMD: -2.94 mg/dl). CONCLUSION: This systematic review evaluated the association between FPG and DHEA, revealing that the administration of DHEA reduces FPG levels. However, we found no association between DHEA administration and IN levels or insulin resistance.

Berberine ameliorates obesity-induced chronic inflammation through suppression of ER stress and promotion of macrophage M2 polarization at least partly via downregulating lncRNA Gomafu.

BACKGROUND: Berberine has been established as a potential drug for inflammation and metabolic disorder. Here, we aimed to explore the effects and the underlying mechanisms of berberine on obesity-induced chronic inflammation. METHODS: Mice were fed with high-fat diet to induce obesity. Inflammation in adipocytes were induced with treatment of free fatty acids. The expression of IL-4, CD206, ARG1 and other markers were used to identify M1 and M2 polarization. The expression of GPR78 and CHOP were used to evaluate endoplasmic reticulum stress. H&E staining was used to reveal the adipose tissue macrophage and adipocytes enlargement. RESULTS: Berberine treatment attenuated endoplasmic reticulum stress and inflammation in obese mice and free fatty acids-treated adipocytes. Overexpression of lncRNA Gomafu partially blocked the protective effects of berberine in free fatty acids-treated adipocytes by increasing endoplasmic reticulum stress. Moreover, Gomafu overexpression partly reversed berberine-induced enhancement of M2 polarization in macrophages. Finally, Gomafu overexpression induced ER stress and inflammation in mice, which were improved by berberine administration. CONCLUSIONS: Berberine improves obesity-induced chronic inflammation by alleviating endoplasmic reticulum stress and consequently promoting macrophage M2 polarization. And these protective effects were mediated at least partly by the suppression of lncRNA Gomafu.

[Observation on short and long-term effects of cervical spondylotic radiculopathy treated with abdominal acupuncture plus Long's bone-setting manipulation].

OBJECTIVE: To compare the short and long-term therapeutic effects on cervical spondylotic radiculopathy (CSR) treated with simple Long's bone-setting manipulation, abdominal acupuncture and abdominal acupuncture plus Long's bone-setting manipulation. METHODS: One hundred and eighty cases of CSR were randomly allocated into abdominal acupuncture plus bone-setting group (combined therapy group), bone-setting group and abdominal acupuncture group, 60 cases in each group. In combined therapy group, the abdominal acupuncture and Long's bone-setting were applied in combination. Abdominal acupuncture was applied to Zhongwan (CV 12), Guanyuan (CV 4), Shiguan (KI 18), Shangqu (KI 17), etc. Long's manipulation, such as bone-setting in head-upward posture and bone-setting in head-lateral posture, was adopted. In bone-setting group and abdominal acupuncture group, Long's bone-setting manipulation and abdominal acupuncture were adopted simply and respectively. The clinical therapeutic effects were compared after 2 courses of treatment (short-term) and 1-month after treatment (long-term) among groups. RESULTS: The short and long-term curative and markedly effective rates in combined therapy group were 80.7% (46/57) and 68.4% (39/57) respectively, which were better than those of 63.64% (35/55), 30.9% (17/55) in bone-setting group and 58.9% (33/56), 50.0% (28/56) in abdominal acupuncture group, separately (all P < 0.05). Moreover, the long-term curative and markedly effective rate in abdominal acupuncture group was superior to that in bone-setting group (P < 0.05). CONCLUSION: Abdominal acupuncture plus Long's bone-setting manipulation has significant efficacy of either short or long-term on CSR, which is superior to the efficacy of either simple abdominal acupuncture or Long's bone-setting manipulation and indicates superimposed effect. Hence, it is one of the better approaches in CSR treatment.

[Observation on therapeutic effect of heat needle combined with herb iontophoresis and western medicine on rheumatoid arthritis].

OBJECTIVE: To search for a therapeutic program for increasing the therapeutic effect of western medicine on rheumatoid arthritis (RA). METHODS: Ninety-six cases of RA were randomly assigned to a treatment group and a control group, 48 cases in each group. The treatment group were treated with heat electroacupuncture instrument with Chinese herb iontophoresis, combined with Meloxicam, Salazosulfamide, and Methotrexate. The control group with simple the western medicine. After treatment of a month, changes of the morning stiff duration, grasp strength, number of tenderness joints, tenderness index, joint rest pain, number of swelling joints, swelling index, assessment of the patient and doctor, and blood rheumatism factor (RF), C-response protein (CRP), erythrocyte sedimentation rate (ESR), the white blood cell (WBC) and platelet counts (PLT) were investigated. RESULTS: The effective rate was 79.2% in the treatment group and 52.1% in the control group, the treatment group being significantly better than the control group (P < 0.01). After treatment of one month, morning stiff duration, average grasp strength of the both hands, tenderness of joint and swelling of joints significantly improved (P < 0.01), with the treatment group being superior to the control group (P < 0.01). After treatment, blood RF, CRP, ESR, WBC and PLT decreased in the two groups (P < 0.01), and the decreases of blood CRP, ESR, PLT in the treatment group were more significantly as compared with the control group (P < 0.01). CONCLUSION: The therapeutic effect of heat needle combined with herb iontophoresis and western medicine is superior to simple medicine for treatment of rheumatoid arthritis.