Objective:To evaluate the effect of acupuncture on postoperative delirium (POD) in diabetic patients undergoing surgery under general anesthesia.Methods:In this randomized controlled trial, 92 diabetic patients of either sex, aged 30-80 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were divided into 2 groups ( n=46 each) using a table of random numbers: control group (group C) and acupuncture group (group A). Group A received acupuncture at the Baihui (GV20), Shenting (GV24) and Sishencong (EX-HN1) acupoints before anesthesia. The needles were retained for 30 min, with manual stimulation applied every 10 min for 10 s each time. After 4 stimulations, routine anesthesia was carried out. Group C received routine anesthesia only. Regional cerebral oxygen saturation was recorded on admission to the operating room (T 0), after anesthesia induction (T 1), at the start of surgery (T 2), at the end of surgery (T 3), and immediately after tracheal extubation (T 4). The POD developed within 3 days after surgery was assessed. The occurrence of needle-related adverse effects such as fainting, subcutaneous bleeding, and local paresthesia was recorded. Results:Compared with group C, the incidence of POD was significantly reduced, and the regional cerebral oxygen saturation was increased at T 1, 4 in group A ( P<0.05). Conclusions:Acupuncture can decrease the development of POD in diabetic patients undergoing surgery under general anesthesia, which is related to an increase in regional cerebral oxygen saturation.

Objective:To evaluate the effect of acupuncture on postoperative delirium (POD) in diabetic patients undergoing surgery under general anesthesia.Methods:In this randomized controlled trial, 92 diabetic patients of either sex, aged 30-80 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were divided into 2 groups ( n=46 each) using a table of random numbers: control group (group C) and acupuncture group (group A). Group A received acupuncture at the Baihui (GV20), Shenting (GV24) and Sishencong (EX-HN1) acupoints before anesthesia. The needles were retained for 30 min, with manual stimulation applied every 10 min for 10 s each time. After 4 stimulations, routine anesthesia was carried out. Group C received routine anesthesia only. Regional cerebral oxygen saturation was recorded on admission to the operating room (T 0), after anesthesia induction (T 1), at the start of surgery (T 2), at the end of surgery (T 3), and immediately after tracheal extubation (T 4). The POD developed within 3 days after surgery was assessed. The occurrence of needle-related adverse effects such as fainting, subcutaneous bleeding, and local paresthesia was recorded. Results:Compared with group C, the incidence of POD was significantly reduced, and the regional cerebral oxygen saturation was increased at T 1, 4 in group A ( P<0.05). Conclusions:Acupuncture can decrease the development of POD in diabetic patients undergoing surgery under general anesthesia, which is related to an increase in regional cerebral oxygen saturation.

AMP-activated protein kinase (AMPK) is a widely distributed and evolutionarily conserved serine/threonine protein kinase present in eukaryotic cells. In regulating cellular energy metabolism, AMPK plays an extremely important role as an energy metabolic kinase. When the body is in a low energy state, AMPK is activated in response to changes in intracellular adenine nucleotide levels and is bound to adenosine monophosphate (AMP) or adenosine diphosphate (ADP). Activated AMPK regulates various metabolic processes, including lipid and glucose metabolism and cellular autophagy. AMPK directly promotes autophagy by phosphorylating autophagy-related proteins in the mammalian target of rapamycin complex 1 (mTORC1), serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1) and type Ⅲ phosphatidylinositol 3-kinase-vacuolar protein-sorting 34 (PIK3C3-VPS34) complexes. AMPK also indirectly promotes autophagy by regulating the expression of downstream autophagy-related genes of transcription factors such as forkhead box O3 (FOXO3), lysosomal function transcription factor EB (TFEB) and bromodomain protein 4 (BRD4). AMPK also regulates mitochondrial autophagy, induces the division of damaged mitochondria and promotes the transfer of the autophagic response to damaged mitochondria. Another function of AMPK is to regulate mitochondrial health by stimulating mitochondrial biogenesis and participating in various aspects of mitochondrial homeostasis regulation. This review discusses the specific regulation of mitochondrial biology and internal environmental homeostasis by AMPK signaling channels as central to the cellular response to energy stress and regulation of mitochondria, highlighting the key role of AMPK in regulating cellular autophagy and mitochondrial autophagy, as well as advances in research on the regulation of mitochondrial homeostasis.

Objective:To explore whether the lipopolysaccharide (LPS)-induced modification of O-linked N-acetylglucosamine (O-GlcNAc) is involved in the inflammatory signaling pathway of endothelial cells.Methods:Human umbilical vein endothelial cells (HUVEC) were cultured in vitro, and cells in logarithmic growth phase were used for experiments. Cells were divided into blank control group, LPS group (2 000 mg/L LPS), O-GlcNAc transferase (OGT) overexpression (OGT-OE)+LPS group (plasmid transfection OGT+2 000 mg/L LPS), protein kinase C (PKC) inhibitor+LPS group (10 μmol/L Go 6983+2 000 mg/L LPS), RhoA inhibitor+LPS group (40 μmol/L Rhoin hydrochloride+2 000 mg/L LPS), phosphatidylinositol-3-kinase (PI3K) inhibitor+LPS group (1 μmol/L SL-2052+2 000 mg/L LPS), serine/threonine kinase (Akt) inhibitor+LPS group (10 μmol/L PP2+2 000 mg/L LPS) and small interfering RNA (siRNA) treated Akt (si-AKT)+LPS group (si-Akt+2 000 mg/L LPS). After 24 hours of LPS treatment, real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the transcription levels of inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)]. The protein expression or phosphorylation of OGT, O-GlcNAc, Akt, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-κB p65 (NF-κB p65), and signal transducer and activator of transcription 3 (STAT3) were determined by Western blotting. Results:Compared with the blank control group, the expression of OGT and the modification of O-GlcNAc in the LPS group were decreased, while the expressions of phosphorylated ERK, p38MAPK, and STAT3 were increased, and the transcript levels of inflammatory cytokines were also significantly increased [IL-6 mRNA (2 -ΔΔCt): 4.71±0.60 vs. 1.03±0.29, TNF-α mRNA (2 -ΔΔCt): 1.89±0.11 vs. 1.04±0.35, ICAM-1 mRNA (2 -ΔΔCt): 2.06±0.18 vs. 1.02±0.21, VCAM-1 mRNA (2 -ΔΔCt): 2.94±0.57 vs. 1.01±0.17, all P < 0.05], indicating that LPS could decrease O-GlcNAc modification, activate inflammatory signaling pathways and increase inflammatory cytokines expression. Compared with the LPS group, the expressions of phosphorylated ERK, p38MAPK, NF-κB p65, and STAT3 in the endothelial cells of the OGT-OE+LPS group were decreased, and the expression of inflammatory factors were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.12±0.01 vs. 0.90±0.17, TNF-α mRNA (2 -ΔΔCt): 0.31±0.01 vs. 0.91±0.14, ICAM-1 mRNA (2 -ΔΔCt): 0.64±0.02 vs. 1.13±0.16, VCAM-1 mRNA (2 -ΔΔCt): 0.11±0.01 vs. 0.93±0.11, all P < 0.05], indicating that the increase of OGT level could inhibit the partial activation of the endothelial inflammatory signal pathway under the LPS stimulation. Compared with the blank control group, the phosphorylation level of Akt in the LPS group was increased. Compared with the LPS group, both OGT expression and O-GlcNAc modification were down-regulated after pretreatment of PKC inhibitor, RhoA inhibitor, PI3K inhibitor, or Akt inhibitor. Compared with the LPS group, the transcript levels of IL-6, TNF-α and ICAM-1 in the PP2+LPS group were significantly decreased [IL-6 mRNA (2 -ΔΔCt): 1.46±0.16 vs. 3.55±0.87, TNF-α mRNA (2 -ΔΔCt): 0.98±0.14 vs. 1.76±0.10, ICAM-1 mRNA (2 -ΔΔCt): 1.39±0.24 vs. 2.04±0.13, all P < 0.05], but there was no significant change in VCAM-1. Compared with the LPS group, the expression of OGT and O-GlcNAc modification in the si-Akt+LPS group were decreased, while the transcript levels of inflammatory cytokines were also significantly decreased [IL-6 mRNA (2 -ΔΔCt): 0.75±0.03 vs. 0.99±0.09, TNF-α mRNA (2 -ΔΔCt): 0.69±0.01 vs. 1.10±0.08, ICAM-1 mRNA (2 -ΔΔCt): 0.76±0.01 vs. 0.99±0.02, VCAM-1 mRNA (2 -ΔΔCt): 0.93±0.08 vs. 1.20±0.21, all P < 0.05], indicating that Akt participated in the action process of LPS on OGT and affected the inflammatory factor expression. Conclusions:The decreased level of O-GlcNAc modification in endothelial cells stimulated with LPS promotes partial activation of inflammatory signaling pathways, mainly involving ERK, p38MAPK, and STAT3, and affects the expression of inflammatory factors. AKT may be involved in the effect of LPS on the inhibition of O-GlcNAc modification.

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear, and currently no effective drugs have been approved for the treatment of NAFLD. Polygonum cuspidatum is a natural traditional Chinese medicine with a long history of application, and studies have shown that it plays an important role in the treatment of NAFLD. This article summarizes related research findings in the active components of Polygonum cuspidatum applied in the treatment of NAFLD, and it is found that the active components of Polygonum cuspidatum can improve insulin resistance, exert an anti-oxidative stress effect, regulate lipid metabolism, improve endoplasmic reticulum stress, and alleviate inflammatory infiltration by regulating the signaling pathways including Nrf2, AMPK, NF-κB, SIRT1, and PPARα, thereby exerting a preventive and therapeutic effect on NAFLD, so as to provide a basis and ideas for developing drugs for NAFLD and exploring related mechanisms.

Objective:To identify the morphological alterations in the Golgi apparatus of skin fibroblasts in spinocerebellar ataxia type 3 (SCA3) patients.Methods:In this study, 3 SCA3 patients and 3 healthy volunteers were obtained in the First Affiliated Hospital of Zhengzhou University from 2016 to 2020. The cytosine, adenine, and guanine repeats of 3 SCA3 patients were 14/76, 20/80 and 21/82, respectively. Tissue mass culture was used to amplify skin fibroblasts derived from SCA3 patients and healthy volunteers. Cell viability and apoptosis were detected using cell counting kit-8 assay and flow cytometry, respectively. Western blotting and immunofluorescence assay were used to detect the protein expression of ataxin-3, Golgi reassembly stacking protein 2 (GORASP2), and Golgi matrix protein 130 (GM130) in the skin fibroblasts. The morphology of the Golgi apparatus in skin fibroblasts was detected using transmission electron microscopy.Results:Tissue culture of skin fibroblasts of both SCA3 patients and healthy volunteers was successfully established. The patient-derived dermal fibroblasts expressing mutant ataxin-3 protein exhibited reduced cell viability ( t=5.06,P=0.007), increased apoptosis ( t=3.77, P=0.020), fragmentation of the Golgi apparatus, increased expression of GM130 ( t=5.23, P=0.006), and decreased expression of GORASP2 ( t=4.35, P=0.012). Transmission electron microscopy revealed that the Golgi apparatus was disorganized in skin fibroblasts. Conclusion:Fragmentation of the Golgi apparatus occurs in the skin fibroblasts of SCA3 patients, and abnormal morphology and structure of the Golgi apparatus may be involved in the pathogenesis of SCA3.

Objective: To explore the association between factors affecting language development and Chinese dyslexia, providing scientific evidence for prevention and intervention of dyslexia. Methods: Twelve elementary schools were selected in Baoan, Shenzhen. The parents and head teachers of 12 868 children in grade 3-5 were surveyed by the Questionnaire for Children s Reading Ability, the Dyslexia Checklist for Chinese Children and the Pupil Rating Scale Revised Screening for Learning Disabilities. Results: The prevalence rate of dyslexia was 2.71%, with 349 children suffering from dyslexia. Gender, parental education and occupations, family income, whether parents work away from home before their child was 3 years old, average time mother spends with her child daily and number of languages spoken in family had statistical significance on dyslexia(all P <0.05). After adjusting for parental education and occupations, and family income, the children who spent more than 1 hour with their mothers per day had a significantly reduced risk of dyslexia (1-2: OR =0.46; 3-4: OR =0.45; 5-6: OR =0.40; >7 h: OR =0.36, P <0.05); the children living in families where two languages were used for communication had a significantly reduced risk of dyslexia( OR=0.74, 95%CI=0.57-0.96, P =0.02). Children with a history of language development disorders had a significantly increased risk of dyslexia( OR=17.30, 95%CI=7.86-38.09, P <0.01). Conclusion Increase of time mother spend with their child daily and paying more attention to the children with a history of language development disorders can help to prevent the occurrence of dyslexia.

Objective To investigate the regulation of mesenchymal stem cells (MSCs) on the expression of tumor necrosis factor-α-induced protein 8-like 2 (TNFAIP8L2, TIPE2) in the peripheral blood-derived macrophages of systemic lupus erythematosus (SLE) patients. Methods The expression of TIPE2 mRNA in peripheral blood mononuclear cells (PBMCs) and macrophages from SLE patients were detected by Quantitative polymerase chain reaction (qPCR). The TIPE2 protein levels in SLE PBMCs and peripheral blood-derived macrophages were detected by western blot, flow cytometry and immunofluorescence staining, respec-tively. Data were analyzed by t test and Spearman correlation analysis. Results The TIPE2 mRNA expres-sion in PBMCs of SLE patients was significantly lower than that of healthy controls [(0.41 ±0.14) vs (1.06±0.39), t=5.376, P<0.01], as well as the TIPE2 protein level [(0.40 ±0.21) vs (1.09 ±0.26), t=2.963, P<0.05]. The expression of TIPE2 mRNA in peripheral blood-derived macrophages from SLE patients was significantly decreased [(0.56±0.24) vs (1.07±0.38), t=5.203, P<0.01). Moreover, TIPE2 mRNA level of peripheral blood-derived macrophages was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI) score (r=-0.60, P<0.01), 24-hour urinary protein (r=-0.46, P<0.05) and erythrocyte sedimentation rate (r=-0.46, P<0.05) in SLE patients. The percentage of TIPE2+cells in peripheral blood-derived macrophages (TIPE2+/CD14+)％ from SLE patients was significantly lower than that in healthy controls [(51.4 ±18.5)％ vs (82.4 ±7.5)％, t=2.679, P<0.05]. After 24 hours co-cultured with MSCs, the TIPE2 mRNA expression in SLE per-ipheral blood-derived macrophages was significantly increased [(2.2 ±0.7) vs (1.0 ±0.3), t=3.729, P<0.05). Immunofluorescence results showed the same increase of TIPE2 protein in SLE peripheral blood-derived macrophages [(0.112 ±0.020) vs (0.074 ±0.016), t=3.268, P<0.05]. Conclusion The TIPE2 level in peripheral blood-derived macrophages of SLE patients are decreased. MSCs upregulate the TIPE2 expression in vitro, suggesting that TIPE2 can be a new target for MSCs in the treatment of SLE.

Objective To investigate the immune regulatory effects of umbilical cord mesenchymal stem cells (UC-MSCs) transplantation on CD4+LAP+Treg cells in the peripheral blood of patients with systemic lupus erythematosus (SLE).Methods CD4+LAP+ Treg cells were detected in the peripheral blood from 30 SLE patients and 30 normal controls by flow cytometry.Five SLE patients received UC-MSCs transplantation,and their peripheral blood was collected before and after 24 hours of cell infusion.The percentages of CD4+ LAP+ T cells were detected by flow cytometry.Data were analyzed with t test and Spearman correlation test.Results The percentage of CD4+LAP+ Treg cells in the peripheral blood of SLE patients [(2.49 ±0.23)％]decreased remarkably compared with healthy controls [(3.35±0.19)％] (r=3.079,P＜0.01),and it was negatively correlated with serum alanine aminotransferase (ALT) [(40±44) U/L,r=-0.51,P＜0.05],AST [(35±53) U/L,r=-0.52,P＜0.05) and ALP [(64±25) U/L,r=-0.53,P＜0.01) level res-pectively.24 hours after UC-MSCs transplantation,the percentages of CD4+LAP+ Treg cells increased signif-icantly in SLE patients[(3.6±0.9)％ vs (2.1±0.6)％,r=3.508,P＜0.05].Conclusion The significantly decreased percentage of CD4+LAP+ Treg cells in patients with SLE suggests thatthey may participate in the pathogenesis of SLE.UC-MSCs transplantation can upregulate the expression of CD4+LAP+Treg cells in SLE patients,and the modulatory effects of UC-MSCs on CD4+LAP+ Treg cells may be one of the mechanisms of UC-MSCs therapy in ameliorating the disease.