Study on the differential hepatotoxicity of raw polygonum multiflorum and polygonum multiflorum praeparata and its mechanism.

BACKGROUND: Polygonum multiflorum (PM), a widely used traditional Chinese medicine herb, is divided into two forms, namely raw polygonum multiflorum (RPM) and polygonum multiflorum praeparata (PMP), according to the processing procedure. Emerging data has revealed the differential hepatotoxicity of RPM and PMP, however, its potential mechanism is still unclear. METHODS: In our study, we investigated the differential hepatotoxicity of RPM and PMP exerted in C57BL/6 mice. First, sera were collected for biochemical analysis and HE staining was applied to examine the morphological alternation of the liver. Then we treated L02 cells with 5 mg / mL of RPM or PMP. The CCK8 and EdU assays were utilized to observe the viability and proliferation of L02 cells. RNA sequencing was performed to explore the expression profile of L02 cells. Western blotting was performed to detect the expression level of ferroptosis-related protein. Flow cytometry was used to evaluate ROS accumulation. RESULTS: In our study, a significant elevation in serum ALT, AST and TBIL levels was investigated in the RMP group, while no significant differences were observed in the PMP group, compared to that of the CON group. HE staining showed punctate necrosis, inflammatory cell infiltration and structural destruction can be observed in the RPM group, which can be significantly attenuated after processing. In addition, we also found RPM could decrease the viability and proliferation capacity of L02 cells, which can be reversed by ferroptosis inhibitor. RNA sequencing data revealed the adverse effect of PM exerted on the liver is closely associated with ferroptosis. Western blotting assay uncovered the protein level of GPX4, HO-1 and FTL was sharply decreased, while the ROS content was dramatically elevated in L02 cells treated with RPM, which can be partially restored after processing. CONCLUSIONS: The hepatotoxicity induced by RPM was significantly lower than the PMP, and its potential mechanism is associated with ferroptosis.

Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway.

Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A. dahurica extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl4) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl4 injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-ß (TGF-ß) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl4-induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1ß, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl4-induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1ß expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1ß expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.

Licochalcone A alleviates abnormal glucolipid metabolism and restores energy homeostasis in diet-induced diabetic mice.

Licochalcone A (LCA) is a bioactive chalcone compound identified in licorice. This study aimed to investigate the effects of LCA on glucolipid metabolism and energy homeostasis, as well as the underlying mechanisms. Blood glucose levels, oral glucose tolerance, serum parameters, and histopathology were examined in high-fat-high-glucose diet (HFD)-induced diabetic mice, with metformin as a positive control. Additionally, changes in key markers related to glucolipid metabolism and mitochondrial function were analyzed to comprehensively assess LCA's effects on metabolism. The results showed that LCA alleviated metabolic abnormalities in HFD-induced diabetic mice, which were manifested by suppression of lipogenesis, promotion of lipolysis, reduction of hepatic steatosis, increase in hepatic glycogenesis, and decrease in gluconeogenesis. In addition, LCA restored energy homeostasis by promoting mitochondrial biogenesis, enhancing mitophagy, and reducing adenosine triphosphate production. Mechanistically, the metabolic benefits of LCA were associated with the downregulation of mammalian target of rapamycin complex 1 and activation of adenosine monophosphate-activated protein kinase, the two central regulators of metabolism. This study demonstrates that LCA can alleviate abnormal glucolipid metabolism and restore energy balance in diet-induced diabetic mice, highlighting its therapeutical potential for the treatment of diabetes.

Limonoids and alkaloids from Tetradium austrosinense (Hand.-Mazz.) T.G.Hartley.

A pair of new enantiomeric indolopyridoquinazoline-type alkaloids, (+)-1,7S,8R- and (-)-1,7R,8S-trihydroxyrutaecarpine (3a and 3b), and a new limonoid-tyrosamine hybrid, austrosinin (8), along with six known alkaloids and limonoids, were isolated from the stems with leaves of Tetradium austrosinense. Their structures were elucidated on the basis of analysis of MS, NMR, ECD and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations, as well as proposed biosynthetic pathway. An anti-inflammatory bioassay in vitro showed 8 had significant immunosuppressive effect against the production of pro-inflammatory cytokine TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

EGFR/MAPK signaling pathway acts as a potential therapeutic target for sulforaphane-rescued heart tube malformation induced by various concentrations of PhIP exposure.

BACKGROUND: 2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyrimidine (PhIP) is a known carcinogen generated mainly from cooking meat and environmental pollutants. It is worth exploring the potential of natural small-molecule drugs to protect against adverse effects on embryonic development. PURPOSE: In this study, we investigated the potential toxicological effects of PhIP on embryonic heart tube formation and the effect of Sulforaphane (SFN) administration on the anti-toxicological effects of PhIP on embryonic cardiogenesis. STUDY DESIGN AND METHODS: First, the chicken embryo model was used to investigate the different phenotypes of embryonic heart tubes induced by various concentrations of PhIP exposure. We also proved that SFN rescues PhIP-induced embryonic heart tube malformation. Second, immunofluorescence, western blot, Polymerase Chain Reaction (PCR) and flow cytometry experiments were employed to explore the mechanisms by which SFN protects cardiac cells from oxidative damage in the presence of PhIP. We used RNA-seq analysis, molecular docking, in situ hybridization, cellular thermal shift assay and solution nuclear magnetic resonance spectroscopy to explore whether SFN protects cardiogenesis through the EGFR/MAPK signaling pathway. RESULTS: The study showed that PhIP might dose-dependently interfere with the C-looping heart tube (mild) or the fusion of a pair of bilateral endocardial tubes (severe) in chick embryos, while SFN administration prevented cardiac cells from oxidative damage in the presence of high-level PhIP. Furthermore, we found that excessive reactive oxygen species (ROS) production and subsequent apoptosis were not the principal mechanisms by which low-level PhIP induced malformation of heart tubes. This is due to PhIP-disturbed Mitogen-activated protein kinase (MAPK) signaling pathway could be corrected by SFN administration. CONCLUSIONS: This study provided novel insight that PhIP exposure could increase the risk of abnormalities in early cardiogenesis and that SFN could partially rescue various concentrations of PhIP-induced abnormal heart tube formation by targeting EGFR and mediating EGFR/MAPK signaling pathways.

Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3ß Signaling Pathway.

OBJECTIVE: To investigate the role of ginsenoside Rd (GRd) in acute myeloid leukemia (AML) cell differentiation. METHODS: AML cells were treated with GRd (25, 50, 100 and 200 µg/mL), retinoic acid (RA, 0.1g/L) and PD98059 (20 mg/mL) for 72 h, cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays, and cell cycle was detected by flow cytometry. Cell morphology and differentiation were observed by Wright-Giemsa staining, peroxidase chemical staining and cellular immunochemistry assay, respectively. The protein expression levels of GATA binding protein 1 (GATA-1), purine rich Box-1 (PU.1), phosphorylated-extracellular signal-related kinase (p-ERK), ERK, phosphorylated-glycogen synthase kinase-3ß (p-GSK3ß), GSK3ß and signal transducer and activator of transcription 1 (STAT1) were detected by Western blot. Thirty-six mice were randomly divided into 3 groups using a random number table: model control group (non-treated), GRd group [treated with 200 mg/(kg·d) GRd] and homoharringtonine (HTT) group [treated with 1 mg/(kg·d) HTT]. A tumor-bearing nude mouse model was established, and tumor weight and volume were recorded. Changes of subcutaneous tumor tissue were observed after hematoxylin and eosin staining. WT1 and GATA-1 expressions were detected by immunohistochemical staining. RESULTS: The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest (p<0.05). GRd treatment induced leukemia cell differentiation, showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation (p<0.05). GRd treatment elicited upregulation of p-ERK, p-GSK-3ß and STAT1 expressions in cells, and reversed the effects of PD98059 on inhibiting the expressions of peroxidase, GATA-1 and PU.1 (P<0.05). After GRd treatment, tumor weight and volume of mice were decreased, and tumor cells underwent massive apoptosis and necrosis (P<0.05). WT1 level was decreased, and GATA-1 level was significantly increased in subcutaneous tumor tissues (P<0.05 or P<0.01). CONCLUSION: GRd might induce the differentiation of AML cells via regulating the ERK/GSK-3ß signaling pathway.

Exploring the potential mechanism of Xuebijing injection against sepsis based on metabolomics and network pharmacology.

Sepsis is a major contributor to the death of critically ill patients globally, in which metabolic disturbance is observed. Xuebijing injection (XBJ), a well-known traditional Chinese medicine, has received approval by the State Food and Drug Administration (SFDA) of China owing to its satisfactory clinical therapeutic effect. Nowadays, it has been applied clinically to the treatment of sepsis, but its effect on metabolic disorders remains unclear. In the present study, we sought to explore its underlying mechanism by employing a combination of network pharmacology and metabolomics. Initially, its protective effects were validated using a sepsis rat model created through cecal ligation puncture (CLP). Subsequently, the metabonomic strategy was utilized to discriminate the differential metabolic markers. Meanwhile, a comprehensive view of the potential ingredient-target-disease network was constructed based on a network pharmacology analysis. Next, the network diagram was constructed by integrating the results of network pharmacology and metabonomics. Finally, qRT-PCR together with Western blot was used to validate the expression levels of the associated genes. Based on our findings, we identified 34 differential metabolites in the sepsis group and 26 distinct metabolites in the XBJ group, with 8 common biological metabolites predominantly associated with arginine and proline metabolism. Through comprehensive analysis, we identified 21 genes that regulate metabolites, and qRT-PCR validation was conducted on six of these genes in both liver and kidney tissues. Additionally, XBJ demonstrated the capability to inhibit the activation of the NF-kB signaling pathway in both liver and kidney tissues, leading to a reduction in the occurrence of inflammatory responses. In summary, our study has validated the complexity of the natural compounds within XBJ and elucidated their potential mechanisms for addressing CLP-induced metabolic disturbances. This work contributes to our understanding of the bioactive compounds and their associated targets, providing insights into the potential molecular mechanisms involved.

Sanguisorba officinalis ethyl acetate extract attenuates ulcerative colitis through inhibiting PI3K-AKT/NF-κB/ STAT3 pathway uncovered by single-cell RNA sequencing.

BACKGROUND: Ulcerative colitis (UC) accounts for the untreatable illness nowadays. Bloody stools are the primary symptom of UC, and the first-line drugs used to treat UC are associated with several drawbacks and negative side effects. S. officinalis has long been used as a medicine to treat intestinal infections and bloody stools. However, what the precise molecular mechanism, the exact etiology, and the material basis of the disease remain unclear. PURPOSE: This work aimed to comprehensively explore pharmacological effects as well as molecular mechanisms underlying the active fraction of S. officinalis, and to produce a comprehensive and brand-new guideline map of its chemical base and mechanism of action. METHODS: First, different polarity S. officinalis extracts were orally administered to the DSS-induced UC model mice for the sake of investigating its active constituents. Using the UPLC-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) technique, the most active S. officinalis (S. officinalis ethyl acetate fraction, SOEA) extract was characterized. Subsequently, the effectiveness of its active fraction on UC was evaluated through phenotypic observation (such as weight loss, colon length, and stool characteristics), and histological examination of pathological injuries, mRNA and protein expression. Cell profile, cell-cell interactions and molecular mechanisms of SOEA in different cell types of the colon tissue from UC mice were described using single-cell RNA sequencing (scRNA-seq). As a final step, the molecular mechanisms were validated by appropriate molecular biological methods. RESULTS: For the first time, this study revealed the significant efficacy of SOEA in the treatment of UC. SOEA reduced DAI and body weight loss, recovered the colon length, and mitigated colonic pathological injuries along with mucosal barrier by promoting goblet cell proliferation. Following treatment with SOEA, inflammatory factors showed decreased mRNA and protein expression. SOEA restored the dynamic equilibrium of cell profile and cell-cell interactions in colon tissue. All of these results were attributed to the ability of SOEA to inhibit the PI3K-AKT/NF-κB/STATAT pathway. CONCLUSIONS: By integrating the chemical information of SOEA derived from UPLC-Q-Orbitrap-HRMS with single-cell transcriptomic data extracted from scRNA-seq, this study demonstrates that SOEA exerts the therapeutic effect through suppressing PI3K-AKT/NF-B/STAT3 pathway to improve clinical symptoms, inflammatory response, mucosal barrier, and intercellular interactions in UC, and effectively eliminates the interference of cellular heterogeneity.

Cobalt-doped hollow polydopamine for oxygen generation and GSH consumption enhanced chemo-PTT combined cancer therapy.

Nanotechnology has revolutionized the field of therapeutics by introducing a plethora of nanomaterials capable of enhancing traditional drug efficacy or paving the way for innovative treatment methods. Within this domain, we propose a novel Cobalt-doped hollow polydopamine nanosphere system. This system, incorporating Doxorubicin loading and hyaluronic acid (HA) surface coating (CoHPDA@DOX-HA), is designed for combined tumor therapy. The overarching aim is to diminish the administration dosage, mitigate the cytotoxic side effects of chemotherapy drugs, augment chemosensitivity within neoplastic tissues, and attain superior results in tumor treatment via combined therapeutic strategies. The targeted molecule, hyaluronic acid (HA), amplifies the biocompatibility of CoHPDA@DOX-HA throughout circulation and fosters endocytosis of the nanoparticle system within cancer cells. This nanosphere system possesses pH sensitivity properties, allowing for a meticulous drug release within the acidic microenvironment of tumor cells. Concurrently, Polydopamine (PDA) facilitates proficient photothermal therapy upon exposure to 808 nm laser irradiation. This process further amplifies the Glutathione (GSH) depletion, and when coupled with the oxygen production capabilities of the Cobalt-doped hollow PDA, significantly enhances the chemo-photothermal therapeutic efficiency. Findings from the treatment of tumor-bearing mice substantiate that even at dosages equivalent to a singular DOX administration, the CoHPDA@DOX-HA can provide efficacious synergistic therapy. Therefore, it is anticipated that multifunctional nanomaterials with Photoacoustic Tomography (PAT) imaging capabilities, targeted delivery, and a controlled collaborative therapeutic framework may serve as promising alternatives for accurate diagnostics and efficacious treatment strategies.

The complete mitochondrial genome of Cuminum cyminum (Apiales: Apiaceae) and phylogenetic analysis.

Cumin (Cuminum cyminum L). belongs to the family Apiaceae and the order Apiales, which is a widely grown spice and medicinal plant in Xinjiang province, China. In the current study, whole genome sequencing of C. cyminum was performed using the Illumina HiSeq 4000 platform, and the complete mitogenome sequence was assembled and annotated. We found that the single circular mitogenome of C. cyminum was 246,721 bp in length, and has about 45.5% GC content. It comprised 73 genes in the coding region (35 protein-coding genes, 18 tRNA genes, 3 rRNA genes, and 15 open-reading frames) and a non-coding region. Phylogenetic analysis indicated that C. cyminum is closely related to Daucus carota and the subtribes Daucinae. The mitogenome of C. cyminum revealed its phylogenetic relationships with other species in the Apiaceae family, which would further help in understanding its evolution.

Longitudinal Changes in Choroidal Structure Following Repeated Low-Level Red-Light Therapy for Myopia Control: Secondary Analysis of a Randomized Controlled Trial.

PURPOSE: Repeated low-level red-light (RLRL) therapy has been confirmed as a novel intervention for myopia control in children. This study aims to investigate longitudinal changes in choroidal structure in myopic children following 12-month RLRL treatment. MATERIALS AND METHODS: The current study is a secondary analysis from a multicenter, randomized controlled trial (NCT04073238). Choroidal parameters were derived from baseline and follow-up swept-source optical coherence tomography scans taken at 1, 3, 6, and 12 months. These parameters included the luminal area (LA), stromal area (SA), total choroidal area (TCA; a combination of LA and SA), and choroidal vascularity index (CVI; ratio of LA to TCA), which were automatically measured by a validated custom choroidal structure assessment tool. RESULTS: A total of 143 children (88.3% of all participants) with sufficient image quality were included in the analysis (n=67 in the RLRL and n=76 in the control groups). At the 12-month visit, all choroidal parameters increased in the RLRL group, with changes from baseline of 11.70×10 3  µm 2 (95% CI: 4.14-19.26×10 3  µm 2 ), 3.92×10 3  µm 2 (95% CI: 0.56-7.27×10 3  µm 2 ), 15.61×10 3  µm 2 (95% CI: 5.02-26.20×10 3  µm 2 ), and 0.21% (95% CI: -0.09% to 0.51%) for LA, SA, TCA, and CVI, respectively, whereas these parameters reduced in the control group. CONCLUSIONS: Following RLRL therapy, the choroidal thickening was found to be accompanied by increases in both the vessel LA and SA, with the increase in LA being greater than that of SA. In the control group, with myopia progression, both the LA and SA decreased over time.

B-seco Limonoids with anti-inflammatory activity from Tetradium fraxinifolium (Hook.) T.G.Hartley.

Fraxinifolines A-F (1-6), six new B-seco limonoids, together with four known A,D-di-seco ones, were isolated from the twigs with leaves of Tetradium fraxinifolium. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR, single-crystal X-ray diffraction and biogenetic pathway. An anti-inflammatory bioassay in vitro showed limonoids 1-3 had significant immunosuppressive effect against the production of pro-inflammatory cytokines (IL-1ß and/or TNF-α) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

[Effect of moxibustion on the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor in ankle synovial tissue of rats with adjuvant arthritis].

OBJECTIVE: To observe the effect of moxibustion on the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in ankle synovial tissue of rats with adjuvant arthritis(AA), so as to explore the mechanism of moxibustion in inhibiting synovial angiogenesis and improving joint symptoms of rheumatoid arthritis. METHODS: Sixty healthy male SD rats were randomly divided into normal group, model group, moxibustion group and medication group, with 15 rats in each group. AA rat model was established by subcutaneous injection of Freund's complete adjuvant into the right hind paw. Rats in the moxibustion group were treated with "Zusanli" (ST36), "Guanyuan" (CV4) and "Ashi" point moxibustion, 20 min each time, once a day, for consecutive 3 weeks. Rats in the medication group were given methotrexate (0.35 mg/kg) intragastric administration, twice a week, for consecutive 3 weeks. Foot plantar volume of rats was measured by toe volume mea-suring instrument. HE staining was used to observe the histopathology of ankle synovium. The protein expressions of HIF-1α and VEGF in ankle synovial tissue were detected by immunohistochemistry and Western blot. RESULTS: Compared with the normal group, the foot plantar volume and the protein expressions of HIF-1α and VEGF in synovial tissue of ankle joint were significantly increased (P<0.01) in the model group, the synovial tissue showed obvious hyperplasia and a large number of neovasculogenesis. Following the interventions, the foot plantar volume and the protein expressions of HIF-1α and VEGF in synovial tissue of ankle joint were significantly decreased (P<0.05, P<0.01) in both moxibustion and medication groups in contrast to the model group, and there was no obvious proliferation of synovial tissue, and only a few neovascularization was observed. Compared with the medication group, the foot plantar volume was decreased (P<0.05) in the moxibustion group. CONCLUSION: Moxibustion can improve joint swelling and inhibit synovial angiogenesis in AA rats, and its mechanism may be related to down-regulating of HIF-1α and VEGF protein expressions.

Shengjiang San alleviated sepsis-induced lung injury through its bidirectional regulatory effect.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection, for which effective therapeutic strategies are still absent. Shengjiang San (SJS), a well-known Traditional Chinese Medicine formula, has been widely used clinically. However, its role in sepsis-induced lung injury remains unclear. METHODS: To explore its specific mechanism, we firstly established a sepsis animal model using cecal ligation and puncture (CLP) and treated MH-S cells with LPS plus ATP. Then, UPLC/Q-TOF-MS/MS was utilized to identify its active ingredients. Network pharmacology analysis was performed to uncover the potential mechanism. HE staining and biochemical analysis were conducted to validate its therapeutic effect. ELISA was applied to detect the release of pro-inflammatory and anti-inflammatory cytokines. Western blot was utilized to detect the protein levels of GSDMD, NLRP3, P65, ASC and caspase-1. RESULTS: SJS could dramatically increase the survival rate of sepsis. In addition, it is able to inhibit the pro-inflammatory cytokines release at day 1 post CLP while promote their production at day 7, indicating SJS could attenuate uncontrolled inflammatory response in the early stage and improve immunosuppression in the late phase. Network pharmacology analysis showed that pyroptosis is the crucial action SJS exerted in the protection of sepsis-induced lung injury. Western blot data implicated SJS could attenuate pyroptosis in early sepsis while enhance in the late phase. CONCLUSIONS: SJS acted to alleviate sepsis-induced lung injury through its bidirectional regulatory effect.

Perioperative, functional, and oncologic outcomes in patients undergoing robot-assisted radical prostatectomy previous transurethral resection of prostate: a systematic review and meta-analysis of comparative trials.

The influence of robot-assisted radical prostatectomy (RARP) on patients who have previously undergone transurethral resection of the prostate (TURP) versus TURP-naive patients is still debatable. The present study aimed to compare perioperative, functional, and oncologic outcomes of RARP between TURP and Non-TURP groups. We systematically searched the databases such as Science, PubMed, Embase, Web of Science, and the Cochrane Library database to identify relevant studies published in English up to August 2022. Review Manager was used to compare various parameters. The study was registered with PROSPERO (CRD42022378126). Eight comparative trials with a total of 4186 participants were conducted. The TURP group had a longer operative time (WMD 22.22 min, 95% CI 8.48, 35.95; p = 0.002), a longer catheterization time (WMD 1.32 day, 95% CI 0.37, 2.26; p = 0.006), a higher estimated blood loss (WMD 23.86 mL, 95% CI 2.81, 44.90; p = 0.03), and higher bladder neck reconstruction rate (OR 8.02, 95% CI 3.07, 20.93; p < 0.0001). Moreover, the positive surgical margin (PSM) was higher in the TURP group (OR 1.49, 95% CI 1.12, 1.98 p = 0.007). However, there was no difference between the two groups regarding the length of hospital stay, transfusion rates, nerve-sparing status, complication rates, long-term continence, potency rates and biochemical recurrence (BCR). Performing RARP on patients who have previously undergone TURP is a safe procedure. Furthermore, the current findings demonstrated that the TURP group had comparable oncologic and long-term functional outcomes to the Non-TURP group.

[Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats].

OBJECTIVE: To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior. METHODS: Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined. RESULTS: Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION: Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

Axial Shortening in Myopic Children after Repeated Low-Level Red-Light Therapy: Post Hoc Analysis of a Randomized Trial.

INTRODUCTION: Axial length (AL) elongation in myopia is considered irreversible. We aimed to systemically report unexpected AL shortening observed in a randomized clinical trial (RCT) after repeated low-level red-light (RLRL) therapy. METHODS: This is a post hoc analysis of a multicenter, single-masked RCT. Two hundred sixty-four myopic children aged 8-13 years allocated to RLRL treatment (intervention group) or a single vision spectacle (SVS, control group) were included. AL was measured using an IOL-master 500 at baseline, 1-, 3-, 6-, and 12-month follow-up visits. AL shortening was defined as AL reduction from baseline to follow-up visits at three cutoffs: > 0.05 mm, > 0.10 mm, and > 0.20 mm. Frequency of AL shortening at different cutoffs was calculated. Analysis was done with intent to treat (ITT). RESULTS: At 12-months follow up, frequency of AL shortening > 0.05 mm was 26/119 (21.85%) and 2/145 (1.38%) for the RLRL group versus the control group, respectively. The frequency was 18/119 (15.13%) versus 0/145 (0%) for AL shortening > 0.10 mm, and 7/119 (5.88%) versus 0/145 (0%), for AL shortening > 0.20 mm, respectively (p < 0.001). Mean AL shortening after 12 months (SD) was -0.156 (0.086) mm in the RLRL group and -0.06 mm in the control group. Age was significantly associated with AL shortening in the multivariable analysis. For the RLRL group that exhibited AL shortening (n = 56), choroidal thickness (ChT) thickening (0.056 mm) could only explain 28.3% of AL shortening (-0.20 mm). CONCLUSION: Nearly a quarter of children had > 0.05 mm AL shortening following 12 months of RLRL therapy, whereas AL shortening rarely occurred among controls. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04073238).

[Effect of thumb-tack needle on gastrointestinal function recovery after cesarean section under the concept of enhanced recovery after surgery].

OBJECTIVE: To observe the synergistic effect and safety of combined use of houpo paiqi mixture and thumb-tack needle on promoting gastrointestinal function recovery after cesarean section. METHODS: Parturients receiving cesarean section were randomly divided into the control group (29 cases), the traditional Chinese medicine (TCM) group (30 cases) and needle+TCM group (30 cases). The control group received only routine postoperative treatment. Besides the treatment as the control group, parturients in the TCM group were given 50 mL houpo paiqi mixture 6 h and 10 h after cesarean section respectively. Besides the treatment as the TCM group, parturients in the needle+TCM group received thumb-tack needle treatment at bilateral Zusanli(ST36), Tianshu(ST25), Shangjuxu(ST37) and Sanyinjiao(SP6), Zhongwan(CV12), Qihai(CV6), with auricular pressure at bilateral otopoints Zigong(Uterus), Wei(Stomach) and Dachang(Large intestine), within 1 h after the parturients returned to the ward after the operation. Each acupoint was pressed for 10 s and performed acupressure every 4 h (except sleeping hours), continuously for 3 d. The time of bowel sound recovery, the time to the first postoperative exhaust and defecation, the time of postoperative semi-fluid diet recovery, incidence of postoperative nausea and vomiting (PONV) and abdominal distention, and abdominal pain VAS score were recorded and analyzed. The safety of the treatments was also evaluated. RESULTS: Compared with the control group, the time of bowel sounds recovery, the time to the first postoperative exhaust and the time of postoperative semi-fluid diet recovery were significantly shortened in the TCM and needle+TCM groups (P<0.01); the time to the first postoperative defecation were significantly shortened (P<0.01), incidence of both abdominal distention and PONV were significantly decreased in the needle+TCM group (P<0.05, P<0.01); incidence of abdominal distention were significantly decreased in TCM group (P<0.05). Compared with the TCM group, the time of bowel sounds recovery, the time to the first postoperative exhaust and defecation, and the time of postoperative semi-fluid diet recovery were significantly shortened (P<0.01), and incidence of both abdominal distention and PONV were significantly decreased in the needle+TCM group (P<0.05). VAS scores of the three groups decreased gradually over time (P<0.01). Compared with the control and TCM groups, VAS scores of the needle+TCM group significantly decreased at 24 h, 48 h and 72 h after operation (P<0.01). No treatment-related adverse reactions were observed during the whole trial. CONCLUSION: On the base of the treatment with houpo paiqi mixture, the addition of thumb-tack needle treatment exerted positive synergistic effect on gastrointestinal function recovery after cesarean section, with high safety, which is worthy of clinical application.