New Insights into TETs in Psychiatric Disorders.

Psychiatric disorders are complex and heterogeneous disorders arising from the interaction of multiple factors based on neurobiology, genetics, culture, and life experience. Increasing evidence indicates that sustained abnormalities are maintained by epigenetic modifications in specific brain regions. Over the past decade, the critical, non-redundant roles of the ten-eleven translocation (TET) family of dioxygenase enzymes have been identified in the brain during developmental and postnatal stages. Specifically, TET-mediated active demethylation, involving the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine and subsequent oxidative derivatives, is dynamically regulated in response to environmental stimuli such as neuronal activity, learning and memory processes, and stressor exposure. Here, we review the progress of studies designed to provide a better understanding of how profiles of TET proteins and 5hmC are powerful mechanisms by which to explain neuronal plasticity and long-term behaviors, and impact transcriptional programs operative in the brain that contribute to psychiatric disorders.

[Content determination of five flavonoids in Tibetan medicine Rhododendron anthopogonoides by quantitative analysis of multi-components by single marker (QAMS)].

To establish a quantitative analysis of multi-components by single marker(QAMS) method for five flavonoids in Rhododendron anthopogonoides and verify its feasibility and applicability in the medicinal materials of R. anthopogonoides. With hyperoside as the internal reference, relative correction factors(RCF) of rutin, quercetin, quercitrin and kaempferol were established by high-performance liquid chromatography(HPLC) analysis. RCFs were used to calculate the content of each component, system durability and relative retention time. Simultaneously, QAMS and external standard method(ESM) were used to determine the content of five flavonoids in 12 batches of R. anthopogonoides from different origins. The results were statistically analyzed to verify the accuracy and feasibility. The fingerprints and cluster analysis data of R. anthopogonoides analyzed and discussed differences among the batches. According to the results, the RCFs of rutin, quercetin, quercetin and kaempferol in R. anthopogonoides were 1.242 6, 0.990 5, 0.535 0, and 0.781 3, respectively. The RCFs represented a good reproducibility under different experimental conditions. Besides, there was no significant difference between QAMS and ESM. Besides, the fingerprint and cluster analysis data showed the consistency between the classification and with the origin distribution of the herbs. In conclusion, the QAMS method shows a good stability and accuracy in the quality control of R. anthopogonoides.

Antioxidant and Anti-inflammatory Capacity of Ferulic Acid Released from Wheat Bran by Solid-state Fermentation of Aspergillus niger.

OBJECTIVE: A strain of Aspergillus niger (A. niger), capable of releasing bound phenolic acids from wheat bran, was isolated. This strain was identified by gene sequence identification. The antioxidant and anti-inflammatory capacity of ferulic acid released from wheat bran by this A. niger strain (FA-WB) were evaluated. METHODS: Molecular identification techniques based on PCR analysis of specific genomic sequences were conducted; antioxidant ability was examined using oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA) assays, and erythrocyte hemolysis assays. RAW264.7 cells were used as a model to detect anti-inflammatory activity. RESULTS: The filamentous fungal isolate was identified to be A. niger. ORAC and CAA assay showed that FA-WB had better antioxidant activity than that of the ferulic acid standard. The erythrocyte hemolysis assay results suggested that FA-WB could attenuate AAPH-induced oxidative stress through inhibition of reactive oxy gen species (ROS) generation. FA-WB could significantly restore the AAPH-induced increase in intracellular antioxidant enzyme activities to normal levels as well as inhibit the intracellular malondialdehyde formation. TNF-a, IL-6, and NO levels indicated that FA-WB can inhibit the inflammation induced by lipopolysaccharide (LPS). CONCLUSION: Ferulic acid released from wheat bran by a new strain of A. niger had good anti-inflammatory activity and better antioxidant ability than standard ferulic acid.

Nonthermal optical emission spectrometry for simultaneous and direct determination of zinc, cadmium and mercury in spray.

A nonthermal optical emission spectrometric (OES) system is developed for the simultaneous multi-element determination of zinc, cadmium and mercury, with a dielectric barrier discharge (DBD) microplasma generated on the nozzle of a pneumatic micronebulizer as the excitation source. After solution nebulization, zinc, cadmium and mercury are directly atomized and excited in the spray by a DBD microplasma for performing optical emission. The emission spectra are measured with a charge-coupled device (CCD) spectrometer. Various important parameters governing the analytical performance of the nonthermal OES system are scrutinized, encompassing the conditions of sample solution introduction, microplasma formation, signal collection and matrix matching for DBD-OES detection. With the characteristic emission lines of Zn 213.9 nm, Cd 228.8 nm and Hg 253.7 nm as the analytical lines for quantification, the detection limits for the simultaneous determination of Zn, Cd and Hg are 22, 1.6, and 10 µg L-1, respectively, and the corresponding linear ranges are 70-6000, 5-1000, and 35-2000 µg L-1, respectively. The accuracy of the present nonthermal OES system is confirmed by the determination of Zn, Cd and Hg in two certified reference materials, i.e., CRM 176 (city waste incineration ash) and GBW 08608 (water). The proposed nonthermal OES system provides a portable instrument for field analysis in emergency with low cost and low consumption.

Nephroprotective Effects of Saponins from Leaves of Panax quinquefolius against Cisplatin-Induced Acute Kidney Injury.

Although cisplatin is an anticancer drug that has activity against malignant tumor, it often causes nephrotoxicity. Previous reports have confirmed that the saponins from the leaves of P. quinquefolium (PQS) exerted many pharmacological activities. However, the renoprotective effects of PQS were still unknown. The purpose of the present research was to discuss renoprotective effect of PQS in a mouse model of cisplatin-induced acute kidney injury (AKI). The levels of blood urea nitrogen (BUN) and serum creatinine (CRE) were evidently increased in cisplatin-intoxicated mice, which were reversed by PQS. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) level and decline of glutathione (GSH) and superoxide dismutase (SOD) activities, was significantly alleviated by PQS pretreatment. The suppression of inflammatory response by PQS was realized through the decrease the mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in kidney tissues, which were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Simultaneously, the overexpression of cytochrome P450 E1 (CYP2E1) and heme oxygenase-1 (HO-1) were attenuated by PQS. Furthermore, the effects of Western blotting demonstrated that PQS administration significantly suppressed the protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase type 4 (Nox4), cleaved Caspase-3, cleaved Caspase-9, Bax, nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), suggesting the inhibition of apoptosis and inflammation response. Overall, PQS may possess protective effects in cisplatin-induced AKI through suppression of oxidative stress, inflammation and apoptosis.

IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice.

AIM: To investigate whether the transfer of the IL-37b gene, a newly identified inhibitor of both innate and adaptive immunity, could improve the therapeutic efficacy of mesenchumal stromal cells (MSCs) in inflammatory bowel disease (IBD). METHODS: The expression of IL-37 in biopsied specimens of the patients with active ulcerative colitis (UC) was detected using RT-PCR and immunohistochemistry. Mice were treated with 3% dextran sulfate sodium (DSS) for 8 days to induce colitis. Before DSS treatment, the mice were injected with MSCs, MSC-eGFP or MSC-IL37b. Their body weight was measured each day, and the colons and spleens were harvested on d 10 for pathological and biochemical analyses. RESULTS: In biopsied specimens of the patients with active UC, the expression of IL-37 was dramatically elevated in inflamed mucosa, mainly in epithelial cells and infiltrating immune cells. Compared to MSC-eGFP or MSCs, MSC-IL37b administration significantly attenuated the body weight and colon length reduction, and decreased the histological score in DSS-induced colitis mice. Furthermore, MSC-IL37b administration increased the percentage of myeloid-derived suppressor cells (MDSCs) among total splenic mononuclear cells as well as the percentage of regulatory T cells (Tregs) among splenic CD4+ T cells in the mice. Moreover, MSC-IL37b administration increased the IL-2+ cells and decreased the IFN-γ+ cells among splenic CD4+ T cells. CONCLUSION: IL-37 is involved in the pathophysiology of UC. IL-37b gene transfer enhances the therapeutic efficacy of MSCs in DSS-induced colitis mice by inducing Tregs and MDSCs and regulating cytokine production.

Transfer of the IL-37b gene elicits anti-tumor responses in mice bearing 4T1 breast cancer.

AIM: IL-37b has shown anti-cancer activities in addition to its anti-inflammatory properties. In this study, we investigated the effects of IL-37b on breast carcinoma growth in mice and to determine the involvement of T cell activation in the effects. METHODS: IL-37b gene was transferred into mouse breast carcinoma cell line 4T1 (4T1-IL37b cells), the expression of secretory IL-37b by the cells was detected, and the effects of IL-37b expression on the cell proliferation in vitro was evaluated. After injection of 4T1 cells or 4T1-IL37b cells into immunocompetent BALB/c mice, immunodeficient BALB/c nude mice and NOD-SCID mice, the tumor growth and survival rate were measured. The proliferation of T cells in vitro was also detected. RESULTS: IL-37b was detected in the supernatants of 4T1-IL37b cells with a concentration of 12.02 ± 0.875 ng/mL. IL-37b expression did not affect 4T1 cell proliferation in vitro. BALB/c mice inoculated with 4T1-IL37b cells showed significant retardation of tumor growth. BALB/c mice inoculated with both 4T1 cells and mitomycin C-treated 4T1-IL37b cells also showed significant retardation of tumor growth. But the anti-cancer activity of IL-37b was abrogated in BALB/c nude mice and NOD-SCID mice inoculated with 4T1-IL37b cells. Recombinant IL-37b slightly promoted CD4(+) T cell proliferation without affecting CD8(+) T cell proliferation. CONCLUSION: IL-37b exerts anti-4T1 breast carcinoma effects in vivo by modulating the tumor microenvironment and influencing T cell activation.

Totally Caged Type I Pro-Photosensitizer for Oxygen-Independent Synergistic Phototherapy of Hypoxic Tumors.

Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors, however, the incompletely inhibited photoactivity of pro-photosensitizer and the limited oxidative phototoxicity of post-photosensitizer are major limitations. It is still a great challenge to address these issues using a single and facile design. Herein, a series of totally caged type I pro-photosensitizers (Pro-I-PSs) are rationally developed that are only activated in tumor hypoxic environment and combine two oxygen-independent therapeutic mechanisms under single-pulse laser irradiation to enhance the phototherapeutic efficacy. Specifically, five benzophenothiazine-based dyes modified with different nitroaromatic groups, BPN 1-5, are designed and explored as latent hypoxia-activatable Pro-I-PSs. By comparing their optical responses to nitroreductase (NTR), it is identified that the 2-methoxy-4-nitrophenyl decorated dye (BPN 2) is the optimal Pro-I-PSs, which can achieve NTR-activated background-free fluorescence/photoacoustic dual-modality tumor imaging. Furthermore, upon activation, BPN 2 can simultaneously produce an oxygen-independent photoacoustic cavitation effect and a photodynamic type I process at single-pulse laser irradiation. Detailed studies in vitro and in vivo indicated that BPN 2 can effectively induce cancer cell apoptosis through synergistic effects. This study provides promising potential for overcoming the pitfalls of hypoxic-tumor photodynamic therapy.

ITPR2 Mediated Calcium Homeostasis in Oligodendrocytes is Essential for Myelination and Involved in Depressive-Like Behavior in Adolescent Mice.

Ca2+ signaling is essential for oligodendrocyte (OL) development and myelin formation. Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) is an endoplasmic reticulum calcium channel and shows stage-dependent high levels in postmitotic oligodendrocyte precursor cells (OPCs). The role and potential mechanism of ITPR2 in OLs remain unclear. In this study, it is revealed that loss of Itpr2 in OLs disturbs Ca2+ homeostasis and inhibits myelination in adolescent mice. Animals with OL-specific deletion of Itpr2 exhibit anxiety/depressive-like behaviors and manifest with interrupted OPC proliferation, leading to fewer mature OLs in the brain. Detailed transcriptome profiling and signal pathway analysis suggest that MAPK/ERK-CDK6/cyclin D1 axis underlies the interfered cell cycle progression in Itpr2 ablated OPCs. Besides, blocking MAPK/ERK pathway significantly improves the delayed OPC differentiation and myelination in Itpr2 mutant. Notably, the resting [Ca2+]i is increased in Itpr2 ablated OPCs, with the elevation of several plasma calcium channels. Antagonists against these plasma calcium channels can normalize the resting [Ca2+]i level and enhance lineage progression in Itpr2-ablated OPCs. Together, the findings reveal novel insights for calcium homeostasis in manipulating developmental transition from OPCs to pre-OLs; additionally, the involvement of OLs-originated ITPR2 in depressive behaviors provides new therapeutic strategies to alleviate myelin-associated psychiatric disorders.

Hypoxic preconditioning accelerates the healing of ischemic intestinal injury by activating HIF-1α/PPARα pathway-mediated fatty acid oxidation.

Hypoxic preconditioning (HPC) has been shown to improve organ tolerance to subsequent severe hypoxia or ischemia. However, its impact on intestinal ischemic injury has not been well studied. In this study, we evaluated the effects of HPC on intestinal ischemia in rats. Intestinal rehabilitation, levels of fatty acid oxidation (FAO) by-products, intestinal stem cells (ISCs), levels of hypoxia-inducible factor 1 subunit α (HIF-1α) and its downstream genes such as peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyltransferase 1a (CPT1A) were assessed at distinct time intervals following intestinal ischemia with or without the interference of HIF-1α. Our data showed that HPC facilitates the restoration of the intestinal structure and enhances the FAO, by boosting intestinal stem cells. Additionally, HIF-1α, PPARα, and CPT1A mRNA and their protein levels were generally up-regulated in the small intestine of HPC rats as compared to the control group. Our vitro experiment also shows low-oxygen induces highly levels of HIF-1α and its downstream genes, with a concurrent increase in FAO products in IEC-6 cells. Furthermore, the above phenomenon could be reversed by silencing HIF-1α. In conclusion, we hypothesize that HPC can stimulate the activation of intestinal stem cells via HIF-1α/PPARα pathway-mediated FAO, thereby accelerating the healing process post ischemic intestinal injury.

[Hennekam syndrome: a case report and review of literature].

OBJECTIVE: To study the clinical characteristics of Hennekam syndrome. METHODS: We described a case of long-term iron deficiency anemia, characteristic facial anomalies, growth retardation, and intestinal lymphangiectasia. To our knowledge, this is the first case of Hennekam syndrome reported in China. Meanwhile, relevant literature was also reviewed. RESULTS: A total of 35 cases of Hennekam syndrome were identified, consisting of 18 males and 17 females (age ranging 0 - 40 years old). Lymphangiectasia, lymphedema, facial anomalies (hypertelorism, flat nasal bridge and flat face) and developmental retardation were the major clinical manifestations of the syndrome. CCBE1 mutation may have played an important role in the pathogenesis of the syndrome. Long-term moderate-to-severe iron deficiency anemia was a distinctive feature of our case. Lymphangiography revealed lymphangiectasia of small intestine and lower limb, as well as thoracic outlet obstruction. Complete elimination of anemia and significant increase of serum albumin level were observed several months after the adhesiolysis procedure of the distal end of thoracic duct. However, anemia and severe hypoalbuminemia relapsed after taking greasy food. CONCLUSIONS: Hennekam syndrome is a rare autosomal recessive syndrome characterized by defective lymphatic development. Congenital lymphangiectasia should be considered in the patients with unexplained developmental retardation and hypoalbuminemia. Moreover, intestinal lymphangiectasia can be a rare cause of gastrointestinal bleeding.

Auricular acupressure for constipation in adults: a systematic review and meta-analysis.

Introduction: Auricular acupressure (AA) has been widely utilized in the management of constipation, with several studies suggesting its efficacy in treating constipation patients. However, the safety and effectiveness of AA in constipation remain uncertain. Hence, the aim of this study was to assess the effectiveness and safety of AA for constipation. Methods and analysis: A total of eight electronic databases and three clinical trial registration platforms were searched from their inception to April 2023 for randomized controlled trials (RCTs) of AA for constipation. The included studies were appraised for quality using the Cochrane Collaboration's Risk of Bias Assessment tool. The quality of evidence was assessed by two independent reviewers employing the Grading of Recommendations Assessment, Development, and Evaluation System (GRADE) evaluation tool. Meta-analysis of data and assessment of publication bias were performed using RevMan 5.4 and STATA 13.0 software, respectively. Results: This review included 34 randomized controlled trials conducted between 2007 and 2023, involving 2,465 participants. The findings of the study indicate that overall, AA is significantly associated with improved CSBMs (MD = 1.22, 95% CI [0.68, 1.77], p < 0.0001, I2 = 0%), BSF (MD = 0.72, 95%CI: [0.15,1.28], p = 0.01, I2 = 82%), CAS (MD = -3.28, 95%CI: [-5.95, -0.60], p = 0.02, I2 = 80%), responder rate (RR = 1.27, 95%CI: [1.16, 1.38], p < 0.00001, I2 = 79%), cure rate (RR = 1.84, 95% CI [1.56, 2.15], p < 0.00001, I2 = 0%), and PAC-QOL (MD = -2.73, 95% CI: [-3.41, -2.04], p < 0.00001, I2 = 98%) compared to the control group. However, no difference in PAC-SYM (MD = -0.15, 95%CI: [-0.38,0.07], p = 0.19, I2 = 67%) was found between the two groups. Additionally, there was no significant difference in adverse events (RR = 0.53, 95% CI: [0.24, 1.21], p = 0.13, I2 = 38%). Conclusion: Based on the available evidence, auricular acupressure appears to be a potentially safe and effective intervention for managing constipation in adults. Nonetheless, the overall quality of evidence for the identified outcomes was assessed as low to very low, highlighting the need for additional high-quality randomized controlled trials to further validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023425033.

Electroacupuncture for post-stroke urinary incontinence: a systematic review and meta-analysis with trial sequential analysis.

Background: The evidence for the effectiveness of electroacupuncture (EA) for post-stroke urinary incontinence (PSUI) patients remains unclear. Therefore, the purpose of this systematic review and meta-analysis was to assess the efficacy of EA for PSUI. Methods and analysis: Eight English and Chinese databases were searched from their inception until 1 August 2023 to collect randomized controlled trials (RCTs) that investigated the effect of EA on PSUI. Two reviewers independently selected studies that met the eligibility criteria, extracted the necessary data, and assessed the risk of bias for included studies using Cochrane Handbook version 5.1.0. Meta-analysis was performed using Review Manager software (version 5.4.1). Publication bias detection was conducted using STATA (version 16.0). Sequential analysis was performed using TSA 0.9.5.10 Beta. The Grading of Recommendations Assessment, Development, and Evaluation System (GRADE) was used for assessing the certainty of evidence. Results: We included 15 RCTs involving a total of 1,414 patients. The narrative analysis revealed that compared with sham EA, genuine EA exhibited greater efficacy in reducing occurrences of 24-h urinary incontinence while also enhancing maximum cystometric capacity (MCC). Moreover, this effect remained significant even during the 3-month follow-up period. Fourteen studies were encompassed within the quantitative analysis. In contrast to active interventions, EA did not yield an improvement in the responder rate (RR 1.53, 95% CI 0.61 to 3.80, p = 0.36). When compared with basic treatments, the combination of EA with them led to a reduction in 24-h urinary incontinence occurrences (MD -0.56, 95% CI -0.60 to -0.52, p < 0.00001), an improvement in MCC (MD 43.23, 95% CI 28.86 to 57.60, p < 0.00001), and a decrease in residual urine volume (RUV; MD -19.99, 95% CI -29.75 to -10.23, p < 0.0001). However, it did not lead to an increase in the responder rate (RR 1.39, 95% CI 0.88 to 2.20, p = 0.16). In comparison to basic treatments combined with active interventions, the amalgamation of EA and them led to an increase in the responder rate (RR 1.24, 95% CI 1.14 to 1.35, p < 0.00001), a reduction in 24-h urinary incontinence occurrences (MD -2.90, 95% CI -5.26 to -0.55, p = 0.02), a decrease in International Consultation on Incontinence Questionnaire-Short Form scores, and an improvement in both MCC (MD 42.11, 95% CI 23.26 to 60.96, p < 0.0001) and RUV (MD 42.11, 95% CI 23.26 to 60.96, p < 0.0001). Furthermore, all reported adverse effects associated with EA were mild. The trial sequential analysis suggested that a sufficient sample size was available to yield results. However, the level of evidence was predominantly assessed as low or very low. Conclusion: Electroacupuncture improved post-stroke urinary incontinence with no serious adverse effects. Caution is warranted due to methodological issues, and more high-quality studies are required to confirm its efficacy and safety.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023449599, Identifier CRD42023449599.

Summary of the application value of ultrasound imaging features in the clinical differential diagnosis of intramuscular capillary-type hemangioma and fibro-adipose vascular anomaly.

Objective: To investigate the value of ultrasonography as a diagnostic aid in differentiating intramuscular capillary-type hemangioma (ICTH) from fibro-adipose vascular anomaly (FAVA). Methods: A retrospective analysis was conducted of the clinical and ultrasound imaging data of 20 patients with ICTH and 45 patients with FAVA who were admitted to and pathologically confirmed in hospital between January 2013 and April 2023. The clinical and ultrasonographic appearances of the lesions in the two groups were compared and analyzed. A stepwise regression analysis was performed, and a joint diagnostic equation was constructed using the final variables selected. The receiver operating characteristic (ROC) curve and indicators, including sensitivity and specificity, were used to evaluate the efficacy of the joint diagnostic model. Results: The two groups of patients suffering from ICTH and FAVA presented a statistically significant difference (P< 0.05) in terms of 'age', 'lesion size', 'fascial tail sign', 'presence of a fatty-tissue-like hyperecho around the lesion', 'blood flow' and 'presence of straight blood capillaries within the lesion'. Finally, the variables 'fascial tail sign' and 'presence of straight blood capillaries within the lesion' were selected to construct the model. The constructed joint diagnostic model had a sensitivity value of 70.0% (95% CI: 59.00-81.00), a specificity value of 98.0% (95% CI: 94.70-100.00) and a ROC curve value of 0.908, indicating the high efficacy of the combined diagnosis method. Conclusions: Ultrasonography can be utilized to differentiate ICTH from FAVA, and the combined diagnosis method can further improve the technique's diagnostic efficacy.

Unilateral cerebral ischemia inhibits optomotor responses of the ipsilateral eye in mice.

A reduction in blood flow to the brain causes stroke and damage to neuronal networks. Cerebral ischemia is frequently associated with loss of visual functions. Because retinal and small cerebral vessels are vulnerable to similar risk factors, the loss of vision could result from concurrent retinal ischemia, and it is not clear if visual functions may be inhibited by cerebral ischemia directly. In this study, the distal middle cerebral artery in the right hemisphere of mice was occluded to produce unilateral cerebral ischemia and subsequent infarction. The layer V neurons expressing YFP in transgenic yellow fluorescent protein in transgenic B6.Cg-Tg(Thy1-YFPH)2Jrs/J mice disappeared in the motor and somatosensory cortex, but not in the visual area. The latencies of flash visual evoked potential recorded from two hemispheres were imbalanced, but did not differ markedly from the latencies recorded in controls. However, the optomotor responses of the ipsilateral eye were significantly reduced by 48 h after occlusion. Our results suggest that focused cerebral ischemia may inhibit ipsilateral eye movement in the absence of damage to the visual cortex. This study may provide a platform for further investigation of the relationship between cortical ischemia and visual function.

The relationship between amyloid-beta and brain capillary endothelial cells in Alzheimer's disease.

Neurovascular dysfunction, as an integral part of Alzheimer's disease, may have an important influence on the onset and progression of chronic neurodegenerative processes. The blood-brain barrier (BBB) pathway is one of the main pathways that mediates the clearance of amyloid-beta (Aß) in the brain parenchyma. A large number of studies have shown that receptors and ATP-binding cassette transporters expressed on endothelial cells play an important role in Aß transport across the BBB, but the specific mechanism is not clear. In this review, we summarize the possible mechanisms of Aß production and clearance, and in particular the relationship between Aß and brain capillary endothelial cells. Aß is produced by abnormal cleavage of the amyloid precursor protein via amyloidogenic processing under pathological conditions. Dysregulation of Aß clearance is considered to be the main reason for the massive accumulation of Aß in the brain parenchyma. Several pathways mediating Aß clearance from the brain into the periphery have been identified, including the BBB pathway, the blood-cerebrospinal fluid barrier and arachnoid granule pathway, and the lymphoid-related pathway. Brain capillary endothelial cells are the key components of Aß clearance mediated by BBB. Receptors (such as LRP1, RAGE, and FcRn) and ATP-binding cassette transporters (such as P-gp, ABCA1, and ABCC1) expressed on endothelial cells play a critical role in Aß transcytosis across the BBB. The toxic effects of Aß can induce dysregulation of receptor and transporter expression on endothelial cells. Excessive Aß exerts potent detrimental cerebrovascular effects by promoting oxidative stress, inducing chronic inflammation, and impairing endothelial structure and functions. All of these are main causes for the reduction in Aß clearance across the BBB and the accumulation of Aß in the brain parenchyma. Therefore, studies on the interactions between Aß and brain capillary endothelial cells, including their receptors and transporters, studies on inhibition of the toxic effects of Aß on endothelial cells, and studies on promoting the ability of endothelial cells to mediate Aß clearance may provide new therapeutic strategies for Aß clearance in Alzheimer's disease.

Modulation of cerebral cortex activity by acupuncture in patients with prolonged disorder of consciousness: An fNIRS study.

Background and objective: Acupuncture is a promising non-pharmacological therapy for patients with prolonged disorder of consciousness (PDOC); however, its underlying mechanism remains uncertain. This study aimed to reveal the modulatory effects of acupuncture on the cerebral cortex activity among patients with PDOC. Materials and methods: Twenty-eight PDOC patients were randomly assigned to the treatment (n = 14) or control (n = 14) group. The treatment group received one session of acupuncture, while the control group received one session of sham acupuncture. All patients underwent evaluation of the functional connectivity and activation response of the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and primary somatosensory cortex (S1) via functional near-infrared spectroscopy. We further explored the potential correlation of the consciousness level and activation response/functional connectivity with acupuncture. Results: Compared to the control group, a single session of acupuncture significantly tended to enhance resting-state functional connectivity (rsFC) in DLPFC-M1, DLPFC-M1, and S1-S1. And the activation level of the DLPFC (both sides) in the acupuncture group is significantly higher than those in sham acupuncture group. However, no significant correlation was found between the consciousness level and activation response/functional connectivity. Conclusion: One session of acupuncture has a significant modulation of rsFC and activation in the DLPFC, M1, and S1 with PDOC patients. Acupuncture-evoked effect may have some functional significance in PDOC patients. This is an important step toward exploring the acupuncture effects on PDOC patients.

Recent Developments of Flavonoids with Various Activities.

Flavonoids, a series of compounds with a C6-C3-C6 structure, mostly originate from plant metabolism. Flavonoids have shown beneficial effects on many aspects of human physiology and health. Recently, many flavonoids with various activities have been discovered, which has led to more and more studies focusing on their physiological and pharmacodynamic activities. The anticancer and anti-viral activities especially have gained the attention of many researchers. Therefore, the discovery and development of flavonoids as anti-disease drugs has great potential and may make a significant contribution to fighting diseases. This review focus on the discovery and development of flavonoids in medicinal chemistry in recent years.

Evaluation of the impact of reference tooth morphology and alignment on model measurement accuracy.

Background: The development of personalized and high-precision dental treatment is inseparable from the accurate measurement and analysis of the model. Compared with traditional plaster models, digital models allow dentists to obtain richer and more detailed inspection results. However, the measurement of digital models in clinical practice usually ignores the influence of the overall three-dimensional (3D) structure of teeth and tooth arrangement on the measurement results. The purpose of this study was to evaluate the effect of calibrated tooth axis and tooth arrangement on tooth width and arch length. Methods: A total of 110 digital models from 80 participants were used to measure teeth width and dental arch length using the following methods: Method A, simple positioning of the proximal and distal of teeth; Method B: calibration of the clinical crown axis; and Method C: calibration of the overall 3D axis of the teeth. The Measurand model included pre- and post-orthodontic models of the same patients to assess the impact of tooth alignment on outcomes. Results: In the aligned dentition, whether the tooth axis was calibrated had no effect on the measurement results. On unaligned dentitions, calibrating the pinion allowed for more accurate measurements, with Method C the closest to the true size. Furthermore, the arrangement of teeth affected the measurement, but there was no continuous linear correlation with arch length discrepancy (ALD). Conclusions: Clinicians should choose appropriate measurement methods according to actual needs when performing model measurement, and should pay attention to the influence of tooth axis, tooth shape, and arrangement on the measurement results.

Dexmededomidine in pediatric unilateral internal inguinal ring ligation.

BACKGROUND: Safe and effective analgesia strategy remains one of the priorities for pediatric inguinal hernia treatment. AIM: To explore safety and efficacy of dexmededomidine monotherapy for postoperative analgesia in children who received laparoscopic unilateral internal inguinal ring ligation. METHODS: This randomized single-center controlled trial included 390 children (aged 1-3 years, ASA grade I-II), randomly divided into a dexmededomidine group (D group), a dexmededomidine + sufentanil group (DS group), and a sufentanil group (S group). The primary endpoint was percentage of children with the Face, Legs, Activity, Cry, and Consolability (FLACC) score ≤ 3 points 2 h after surgery. RESULTS: The comparisons of the FLACC scores at 2, 4, 6, 8, 12, and 24 h were not significantly different among the three groups (P > 0.05). The sedative effects in the D group were significantly better than those in the S group (P > 0.05), but not significantly different from those in the DS group. The incidence of nausea and vomiting was significantly lower in the D group than in the S group and DS group (P > 0.05). CONCLUSION: Analgesic effects of dexmededomidine monotherapy are comparable to those of sufentanil alone or in combination with dexmededomidine for children who underwent laparoscopic unilateral internal inguinal ring ligation, with better sedative effects and a lower incidence of adverse events.