Pseudomyopia treated with auricular point sticking combined with periocular needle-embedding therapy and prevention of true myopia: a multicenter randomized controlled trial. / è€³ç©´è´´åŽ‹è”åˆçœ¼å‘¨æ¿é’ˆæŠ€æœ¯é¢„é˜²å‡æ€§è¿‘è§†å‘çœŸæ€§è¿‘è§†è¿›å±•ï¼šå¤šä¸­å¿ƒéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical effect and safety of auricular point sticking combined with periocular needle-embedding therapy for pseudomyopia and prevention of true myopia. METHODS: A total of 269 children with pseudomyopia were randomized into an observation group (134 cases, 2 cases dropped out) and a control group (135 cases, 5 cases dropped out). In the control group, the healthy education was provided. In the observation group, besides the intervention as the control group, the auricular point sticking was delivered at gan (CO12), pi (CO13), xin (CO15) and yan (LO5) on one ear in each treatment, combined with periocular needle-embedding technique at bilateral Cuanzhu (BL 2), Yuyao (EX-HN 4) and Sibai (ST 2). There were 2 weeks of interval after 4 weeks of treatment. One course of treatment was composed of 6 weeks and 2 courses were required. Separately, before treatment, after 6 and 12 weeks of treatment, and after 12 weeks (the 1st follow-up visit) and 24 weeks (the 2nd follow-up visit) of treatment completion, the spherical equivalent (SE), SE progression, axial length (AL) progression, accommodative amplitude (AMP), the score of the TCM symptom and the general symptom were observed in the two groups. The safety and compliance were evaluated in the two groups. RESULTS: After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, SE increased when compared with that before treatment in the two groups (P<0.05), and AMP was larger than that before treatment in the observation group (P<0.05). After 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the progression of SE was slower in the observation group compared with that in the control group (P<0.01, P<0.001). After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the progression of AL in the observation group was lower than that of the control group (P<0.05, P<0.01, P<0.001); and in the 1st and 2nd follow-up visits, AMP of the observation group was larger when compared with that in the control group (P<0.05, P<0.001). After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the total scores of TCM symptom and general symptom were reduced in comparison with those before treatment in the observation group (P<0.05); after 6 and 12 weeks of treatment, the total scores of TCM symptom and general symptom were lower than those before treatment in the control group (P<0.05). In the 1st and 2nd follow-up visits, the difference of the total score of TCM symptom and general symptom in the observation group was larger than that of the control group (P<0.05). In the observation group, compared with the control group, the scores for pale/dark complexion in the 1st and 2nd follow-up visits and that for lassitude in the 2nd follow-up visit were lower (P<0.05), the score for poor concentration after 12 weeks of treatment and that for poor sleep and memory in the 2nd follow-up visit were lower (P<0.05). There were no adverse reactions in the two groups. The compliance was 98.5% in the observation group and was 96.3% in the control group, without statistical difference (P>0.05). CONCLUSIONS: On the basis of health education, auricular point sticking combined with periocular needle-embedding therapy can effectively prevent from true myopia, control the increase of SE, delay the growth of AL and improve AMP in children with pseudomyopia. This compound therapeutic regimen can relieve the general symptom and comprehensively prevent from myopia through multiple approaches, with high safety and satisfactory compliance.

Multifunctional coatings of nickel-titanium implant toward promote osseointegration after operation of bone tumor and clinical application: a review.

Metal implants, especially Ni-Ti shape memory alloy (Ni-Ti SMA) implants, have increasingly become the first choice for fracture and massive bone defects after orthopedic bone tumor surgery. In this paper, the internal composition and shape memory properties of Ni-Ti shape memory alloy were studied. In addition, the effects of porous Ni-Ti SMA on osseointegration, and the effects of surface hydrophobicity and hydrophilicity on the osseointegration of Ni-Ti implants were also investigated. In addition, the effect of surface coating modification technology of Ni-Ti shape memory alloy on bone bonding was also studied. Several kinds of Ni-Ti alloy implants commonly used in orthopedic clinic and their advantages and disadvantages were introduced. The surface changes of Ni-Ti alloy implants promote bone fusion, enhance the adhesion of red blood cells and platelets, promote local tissue regeneration and fracture healing. In the field of orthopaedics, the use of Ni-Ti shape memory alloy implants significantly promoted clinical development. Due to the introduction of the coating, the osseointegration and biocompatibility of the implant surface have been enhanced, and the success rate of the implant has been greatly improved.

In Vitro Profiling of Toxicity Effects of Different Environmental Factors on Skin Cells.

The skin is constantly exposed to a variety of environmental threats. Therefore, the influence of environmental factors on skin damage has always been a matter of concern. This study aimed to investigate the cytotoxic effects of different environmental factors, including cooking oil fumes (COFs), haze (PM2.5), and cigarette smoke (CS), on epidermal HaCaT cells and dermal fibroblast (FB) cells. Cell viability, intracellular reactive oxygen species (ROS) generation, inflammatory cytokine levels, and collagen mRNA expression were used as toxicity endpoints. Additionally, the effects of ozone (O3) on cell viability and release of inflammatory cytokines in 3D epidermal cells were also examined. The results showed that the organic extracts of CS, COFs, and PM2.5 significantly inhibited the viability of HaCaT and FB cells at higher exposure concentrations. These extracts also increased intracellular ROS levels in FB cells. Furthermore, they significantly promoted the release of inflammatory cytokines, such as IL-1α and TNF-α, in HaCaT cells and down-regulated the mRNA expression of collagen I, III, IV, and VII in FB cells. Comparatively, SC organic extracts exhibited stronger cytotoxicity to skin cells compared to PM2.5 and COFs. Additionally, O3 at all test concentrations significantly inhibited the viability of 3D epidermal cells in a concentration-dependent manner and markedly increased the levels of TNF-α and IL-1α in 3D epidermal cells. These findings emphasize the potential cytotoxicity of COFs, PM2.5, CS, and O3 to skin cells, which may lead to skin damage; therefore, we should pay attention to these environmental factors and take appropriate measures to protect the skin from their harmful effects.

Experimental study on new structure teeth in a high-temperature environment.

In high-temperature drilling, especially in high-temperature geothermal drilling, cone bits often experience common and severe tooth loss. This issue significantly reduces the cone bit's service life and has a detrimental impact on drilling efficiency. The quality of the fixed teeth plays a crucial role in the performance of the cone bit. In high-temperature environments, conventional methods fail to meet the requirements for securing the cone bit's teeth. Therefore, to address the tooth loss problem in high-temperature drilling, a new tapered tooth structure is proposed. Laboratory experiments were conducted to secure teeth with varying tapers at both normal and high temperatures. The results revealed that the maximum fastening force increased progressively with the degree of taper, reaching its peak at C50. Compared to conventional cylindrical teeth, the maximum fastening force increased by approximately 88.6%-271.1% at different temperatures. The tapered structure demonstrated superior tooth-fixing strength. The maximum fastening force is the smallest at 300 °C, approximately 23.7%-61.2% lower than at normal temperature. Under the same interference conditions, the maximum fastening force increased with greater taper. With interference values of 0.075, 0.095, and 0.115, the maximum fastening force increased by 48.9%-175.1%, 14%-141.6%, and 53%-271.1%, respectively, when compared to cylindrical teeth with C300, C200, C100, and C50 tapers. The tapered structure exhibited superior tooth-fixing strength and significantly enhanced tooth retention strength at high temperatures.

Effects of trichlorobisphenol A on the expression of proteins and genes associated with puberty initiation in GT1-7 cells and the relevant molecular mechanism.

This study evaluated the effects of Cl3BPA on kisspeptin-G-protein coupled receptor 54 (GPR54)/gonadotropin-releasing hormone (GnRH) (KGG) signals and analyzed the roles of estrogen receptor alpha (ERɑ) and G-protein coupled estrogen receptor 1 (GPER1) in regulating KGG signals. The results showed that Cl3BPA at 50 µM increased the levels of intracellular reactive oxygen species (ROS) and GnRH, upregulated the protein levels of kisspeptin and the expression of fshr, lhr and gnrh1 genes related to KGG in GT1-7 cells. In addition, 50 µM Cl3BPA significantly upregulated the phosphorylation of extracellular regulated protein kinases 1/2 (Erk1/2), the protein levels of GPER1 and the expression of the gper1 as well as the most target genes associated with mitogen-activated protein kinase (MAPK)/Erk1/2 pathways. Specific signal inhibitor experiments found that Cl3BPA activated KGG signals by activating the GPER1-mediated MAPK/Erk1/2 signaling pathway at the mRNA level. A docking test further confirmed the interactions between Cl3BPA and GPER1. The findings suggest that Cl3BPA might induce precocious puberty by increasing GnRH secretion together with KGG signaling upregulation, which is driven by GPER1-mediated signaling pathway. By comparison, ClxBPAs with fewer chlorine atoms had more obvious effects on the expression of proteins and partial genes related to KGG signals in GT1-7 cells.

Astragaloside IV protects cardiomyocytes from hypoxic injury by regulating endoplasmic reticulum stress via eIF2α/CHOP signaling pathway.

Endoplasmic reticulum stress (ER stress) is suggested to promote cardiomyocyte apoptosis and ultimately lead to ischemic injury. Inhibition of ER stress-induced apoptosis may be a therapeutic strategy for MI injury. Astragaloside-IV (AST) from Astragalus membranaceus (Fisch) Bge, was reported to have cardioprotective properties. In this study, we investigated the protective effect of AST on cardiomyocytes against hypoxia injury by regulating ER stress and inhibiting apoptosis. H9c2 cardiomyocytes were divided into three groups, normal group, hypoxia group and AST group. Cell viability was determined by CCK-8 assay. Intracellular reactive oxygen species (ROS) production was detected by DCFH-DA (2,7- dichloro-dihydrofluorescein diacetate) florescent staining. The study showed that AST treatment could significantly increase the cell viability of H9c2 cells exposed to hypoxia. Furthermore, AST could restrain cell apoptosis and decrease the production of ROS. Compared with normal group, the protein levels of Bax, caspase-3, caspase-9, GRP78, p-eIF2α, and CHOP were enhanced in the hypoxia group, whereas the protein level of Bcl-2 was dramatically reduced. Compared with hypoxia group, AST markedly inhibited the phosphorylation of eIF2α and the expression of caspase-3, caspase-9 and CHOP, and promoted the protein expression of Bcl-2. Thus, AST can inhibit the ER stress-mediated apoptosis, partly through the eIF2α/CHOP pathway suppression to inhibit ER stress.

Available and novel plant-based carbon dots derived from Vaccaria Semen carbonisata alleviates liver fibrosis.

Background: Liver fibrosis represents an intermediate stage in the progression of liver disease, and as of now, there exists no established clinical therapy for effective antifibrotic treatment. Purpose: Our aim is to explore the impact of Carbon dots derived from Vaccaria Semen Carbonisata (VSC-CDs) on carbon tetrachloride-induced liver fibrosis in mice. Methods: VSC-CDs were synthesized employing a modified pyrolysis process. Comprehensive characterization was performed utilizing various techniques, including transmission electron microscopy (TEM), multiple spectroscopies, X-ray photoelectron spectroscopy (XPS), and high-performance liquid chromatography (HPLC). A hepatic fibrosis model induced by carbon tetrachloride was utilized to evaluate the anti-hepatic fibrosis effects of VSC-CDs. Results: VSC-CDs, exhibiting a quantum yield (QY) of approximately 2.08%, were nearly spherical with diameters ranging from 1.0 to 5.5 nm. The VSC-CDs prepared in this study featured a negative charge and abundant chemical functional groups. Furthermore, these particles demonstrated outstanding dispersibility in the aqueous phase and high biocompatibility. Moreover, VSC-CDs not only enhanced liver function and alleviated liver damage in pathomorphology but also mitigated the extent of liver fibrosis. Additionally, this study marks the inaugural demonstration of the pronounced activity of VSC-CDs in inhibiting inflammatory reactions, reducing oxidative damage, and modulating the TGF-ß/Smad signaling pathway. Conclusion: VSC-CDs exerted significant potential for application in nanodrugs aimed at treating liver fibrosis.

Efficient Strategy for Radiative Cooling Based on Ultra-Broad-Band Infrared Regulation of Flexible Bilayer Film.

Flexible thermal radiation films with adjustable broad-band infrared radiation could maintain various heat-generating electronic devices working stably in corresponding operating temperatures, making them good candidates for radiative cooling (RC) material. However, the controllable radiation peaks of the metamaterial were narrow, and manipulation was a time-consuming and complex process. Herein, we design a simple TiN/Si bilayer film with controllable broad-band radiation peaks at a thermal radiation wavelength of 3.5-20 µm by impedance matching. Meanwhile, the different bilayer films applied to aluminum devices at different temperatures exhibit outstanding heat dissipation efficiency and maintain the corresponding equilibrium temperature to ensure that devices work stably for a long time. Moreover, the bilayer films deposited on the flexible PI substrates exhibit preferable thermostability and higher tensile strength than existing radiative cooling materials deposited on PDMS, PE, PMMA or TPX, etc. This work provides an effective strategy to realize efficient radiation cooling for flexible electronic devices and spacecraft appendages.

Comparison of Ussing Chamber and Caco-2 Model in Evaluation of Intestinal Absorption Mechanism of Compounds from Different BCS Classifications.

BACKGROUND: Oral bioavailability (F), which is evaluated by permeability and solubility, is one of the key parameters in drug discovery. Currently, Caco-2 and Ussing chamber are both used in the study of intestinal permeability of drugs at different stages of drug development. However, comparative research between the Ussing chamber and Caco-2 for predicting the intestinal availability data (Fa×Fg) in humans has not been reported. METHODS: In the present study, we evaluated the permeability of 22 drugs in rat intestines by Ussing chamber and compared them with the reported permeability data from Caco-2. In addition, the active transport of gabapentin was evaluated by Ussing Chamber. RESULTS: Intestine segments were selected by corresponding absorption site for Ussing chamber analysis. BCS Class I and II compounds were more absorbed in the duodenum and jejunum, and Class III and IV compounds were more absorbed in the ileum. Papp values in the Caco-2 model were moderately correlated with human Fa×Fg (R2=0.722), and the Papp of the rat in the Ussing chamber revealed a better correlation with human Fa×Fg (R2=0.952). In addition, we also used the Ussing chamber to identify the transporter of gabapentin, and the results showed that the active absorption of gabapentin was related to LAT1. CONCLUSION: Ussing chamber combined with rat intestinal tissue would be a significant tool for predicting the intestinal absorption and metabolism of compounds with diverse physiochemical characteristics.

Pseudokordiimonas caeni gen. nov., sp. nov., isolated from activated sludge.

A bacterial strain designated as LB-31T was isolated from activated sludge. Strain LB-31T was Gram-stain-negative, non-spore-forming and rod-shaped with a single polar flagellum. The isolate grew at 15-37 °C, pH 5.5-8.5 and 0.5-8.5 % (w/v) NaCl. Genome sequencing revealed a genome size of 3.55 Mb, a G+C content of 61.1 mol% and 3222 protein-coding genes. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain LB-31T formed a phyletic lineage that was distinct from the three known genus within the family Kordiimonadaceae. The 16S rRNA gene sequence similarity of strain LB-31T to all recognized bacterial species was no more than 94 %. Average nucleotide identity and digital DNA-DNA hybridization values between strain LB-31T and its phylogenetic neighbours were below 72 and 22 %, respectively. The average amino acid identity values for strain LB-31T and its closed phylogenetic neighbours Kordiimonas and Eilatimonas were below 63%, supporting that strain LB-31T was a member of a novel genus. The predominant respiratory quinone is Q-10, the fatty acid profile predominantly consisted of iso-C17 : 1 ω9c, iso-C17 : 0, iso-C15 : 0 and summed feature 3 (comprising iso-C15 : 02-OH/C16 : 1 ω7c), and the major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The combined genotypic and phenotypic data show that strain LB-31T represents a novel species of a novel genus in the family Kordiimonadaceae, for which the name Pseudokordiimonas caeni gen. nov., sp. nov. is proposed. The type strain of Pseudokordiimonas caeni is LB-31T (=GDMCC 1.3625T=KCTC 92687T).

Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.

Osteosarcoma (OS) is a primary malignant bone tumor that occurs in children and adolescents, and the PI3K/AKT pathway is overactivated in most OS patients. MicroRNAs (miRNAs) are highly conserved endogenous non-protein-coding RNAs that can regulate gene expression by repressing mRNA translation or degrading mRNA. MiRNAs are enriched in the PI3K/AKT pathway, and aberrant PI3K/AKT pathway activation is involved in the development of osteosarcoma. There is increasing evidence that miRNAs can regulate the biological functions of cells by regulating the PI3K/AKT pathway. MiRNA/PI3K/AKT axis can regulate the expression of osteosarcoma-related genes and then regulate cancer progression. MiRNA expression associated with PI3K/AKT pathway is also clearly associated with many clinical features. In addition, PI3K/AKT pathway-associated miRNAs are potential biomarkers for osteosarcoma diagnosis, treatment and prognostic assessment. This article reviews recent research advances on the role and clinical application of PI3K/AKT pathway and miRNA/PI3K/AKT axis in the development of osteosarcoma.

Ultrasmall and highly biocompatible carbon dots derived from natural plant with amelioration against acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) refers to a tricky clinical disease, known by its high morbidity and mortality, with no real specific medicine for AKI. The carbonization product from Pollen Typhae (i.e., Pu-huang in China) has been extensively employed in clinic, and it is capable of relieving the renal damage and other diseases in China since acient times. RESULTS: Inspired by the carbonization process of Traditional Chinese Medicine (TCM), a novel species of carbon dots derived from Pollen Typhae (PT-CDs) was separated and then collected using a one-pot pyrolysis method. The as-prepared PT-CDs (4.85 ± 2.06 nm) with negative charge and abundant oxygenated groups exhibited high solubility, and they were stable in water. Moreover, the rhabdomyolysis (RM)-induced AKI rat model was used, and it was first demonstrated that PT-CDs had significant activity in improving the level of BUN and CRE, urine volume and kidney index, and histopathological morphology in RM-induced AKI rats. It is noteworthy that interventions of PT-CDs significantly reduced degree of inflammatory reaction and oxidative stress, which may be correlated with the basial potential mechanism of anti-AKI activities. Furthermore, cytotoxicity assay and biosafety evaluation exhibited high biocompatibility of PT-CDs. CONCLUSION: This study offers a novel relieving strategy for AKI based on PT-CDs and suggests its potential to be a related candidate for clinical applications.

Tetrachlorobisphenol A and bisphenol AF induced cell migration by activating PI3K/Akt signaling pathway via G protein-coupled estrogen receptor 1 in SK-BR-3 cells.

Different subtypes of breast cancer express positively G protein-coupled estrogen receptor 1 (GPER1). Our previous studies found that tetrachlorobisphenol A (TCBPA) and bisphenol AF (BPAF) significantly promoted SK-BR-3 cell proliferation by activating GPER1-regulated signals. The present study further investigated the effects of TCBPA and BPAF on the migration of SK-BR-3 cells and examined the role of phosphatidylinositol 3-kinase-protein kinase B (PI3K/Akt) and its downstream signal targets in this process. We found that low-concentration BPAF and TCBPA markedly accelerated the migration of SK-BR-3 cells and elevated the mRNA levels of target genes associated with PI3K/Akt and mitogen-activated protein kinase (MAPK) signals. TCBPA- and BPAF-induced upregulation of target genes was significantly reduced by GPER1 inhibitor G15, the PI3K/Akt inhibitor wortmannin (WM), and the epidermal growth factor receptor (EGFR) inhibitor ZD1839 (ZD). G15 and WM also decreased cell migration induced by TCBPA and BPAF. The findings revealed that TCBPA and BPAF promoted SK-BR-3 cell migration ability by activating PI3K/Akt signaling pathway via GPER1-EGFR.

Smart nanogels for cancer treatment from the perspective of functional groups.

Introduction: Cancer remains a significant health challenge, with chemotherapy being a critical treatment modality. However, traditional chemotherapy faces limitations due to non-specificity and toxicity. Nanogels, as advanced drug carriers, offer potential for targeted and controlled drug release, improving therapeutic efficacy and reducing side effects. Methods: This review summarizes the latest developments in nanogel-based chemotherapy drug delivery systems, focusing on the role of functional groups in drug loading and the design of smart hydrogels with controlled release mechanisms. We discuss the preparation methods of various nanogels based on different functional groups and their application in cancer treatment. Results: Nanogels composed of natural and synthetic polymers, such as chitosan, alginate, and polyacrylic acid, have been developed for chemotherapy drug delivery. Functional groups like carboxyl, disulfide, and hydroxyl groups play crucial roles in drug encapsulation and release. Smart hydrogels have been engineered to respond to tumor microenvironmental cues, such as pH, redox potential, temperature, and external stimuli like light and ultrasound, enabling targeted drug release. Discussion: The use of functional groups in nanogel preparation allows for the creation of multifunctional nanogels with high drug loading capacity, controllable release, and good targeting. These nanogels have shown promising results in preclinical studies, with enhanced antitumor effects and reduced systemic toxicity compared to traditional chemotherapy. Conclusion: The development of smart nanogels with functional group-mediated drug delivery and controlled release strategies represents a promising direction in cancer therapy. These systems offer the potential for improved patient outcomes by enhancing drug targeting and minimizing adverse effects. Further research is needed to optimize nanogel design, evaluate their safety and efficacy in clinical trials, and explore their potential for personalized medicine.

The Relationship between Bullshit Receptivity and Willingness to Share Misinformation about Climate Change: The Moderating Role of Pregnancy.

Widespread dissemination of misinformation about climate change has seriously harmed the health of future generations and the world. Moreover, misinformation-sharing behaviors exhibit strong individual characteristics. However, research is limited on the antecedents of and mechanism underlying the willingness to share misinformation about climate change in terms of individual personalities and physiological states. Accordingly, we surveyed 582 women (224 pregnant) using a questionnaire and constructed a moderated mediation model to explore the relationships among individuals' bullshit receptivity, belief in misinformation about climate change, willingness to share misinformation about climate change, and pregnancy. The results showed that: (1) bullshit receptivity is positively related to the willingness to share misinformation about climate change; (2) belief in misinformation about climate change mediates the relationship between bullshit receptivity and willingness to share misinformation about climate change; and (3) for individuals with higher bullshit receptivity, pregnancy exacerbates the detrimental effects of bullshit receptivity on belief in misinformation about climate change.

Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor.

Environmental estrogens can promote the growth, migration, and invasion of breast cancer. However, few studies evaluate adverse health impacts of environmental estrogens on other organs of breast cancer patients. Therefore, the present study investigated the effects of environmental estrogen bisphenol AF (BPAF) on the main organs of female Balb/cA nude mice with SK-BR-3 xenograft tumor by detecting the organ development and gene expression of targets associated with G protein-coupled estrogen receptor 1 (GPER1)-mediated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways in hypothalamus, ovary, uterus, liver, and kidney. The results showed that BPAF at 20 mg/kg bw/day markedly increased the uterine weight and the uterine coefficient of nude mice compared to SK-BR-3 bearing tumor control, indicating that BPAF promoted the growth of uterus due to its estrogenic activity. Additionally, BPAF significantly up-regulated the mRNA relative expression of most targets related to nuclear estrogen receptor alpha (ERα) and GPER1-mediated signaling pathways in the hypothalamus, followed by the ovary and uterus, and the least in the liver and kidney, indicating that BPAF activated different estrogen activity related targets in different tissues. In addition, BPAF markedly up-regulated the mRNA expression of GPER1 in all tested tissues, and the molecular docking showed that BPAF could dock into GPER1. Because gene change is an early event of toxicity response, these findings suggested that BPAF might aggravate the condition of breast cancer patients through exerting its estrogenic activity via the GPER1 pathway in various organs.

Analysis of aerobic exercise influence on intraocular pressure and ocular perfusion pressure in patients with primary open-angle glaucoma: A randomized clinical trial.

Purpose: To investigate the change pattern of ocular perfusion pressure (OPP) and intra-ocular pressure (IOP) after short-term and long-term aerobic exercise. Methods: In this prospective, single-masked, randomized clinical trial, 123 patients with a primary open angle glaucoma that locally used prostaglandin analog alone were randomly divided into the exercise and control groups. In the short-term study, all individuals underwent a cycling exercise at moderate intensity (20% Wmax for 10 minutes) and high intensity (60% Wmax for 5 minutes). During the long-term study, the exercise group is characterized by regular jogging exercise lasting for 30 minutes during 6: 00-10: 00 in the morning for 3 months, with the exercise frequency of at least 20 times per month, and with the intensity reflected by the target heart rate. The control group is designed as a group with irregular exercise. Results: After short-term aerobic exercise, IOP significantly decreased, whereas the ocular perfusion pressure (OPP) significantly increased. The decreasing amplitude of IOP is related to the baseline of IOP, the intensity of exercise, gender, and so on. After 3 months of long-term exercise, the changes in the IOP level of the exercise group indicated a decreasing trend. Conclusion: The significant decrement of IOP and the increment of OPP suggest that aerobic exercise is beneficial for patients with primary open-angle glaucoma and appropriate aerobic exercise is appropriate in treating glaucoma patients. Trial registration: ChiCTR, ChiCTR-TRC-10001055. Registered one October 2010-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj = 8483.

Mingmu Xiaoyao granules regulate the PI3K/Akt/mTOR signaling pathway to reduce anxiety and depression and reverse retinal abnormalities in rats.

Objective: To investigate the effects of Mingmu Xiaoyao granules (MMXY) on the morphology and function of the retina and the mechanism of PI3K/Akt/mTOR pathway-related proteins in rats with anxiety and depression induced by chronic unpredictable mild stress (CUMS). Methods: Fifty-two male Sprague Dawley rats were randomly allocated to either a control (n = 14) or a simulated CUMS group (n = 38). The CUMS model was established successfully at 4 weeks. Six rats in each group were randomly selected to be sacrificed and their retinas isolated for histological examination. At 5 weeks, rats in the CUMS group were randomly allocated to the following groups: Model (CUMS + pure water), MMXY-H (CUMS + MMXY 7.2 g/kg/d), MMXY-L (CUMS + MMXY 3.6 g/kg/d), and CBZ (CUMS + Carbamazepine 20 mg/kg/d), with eight rats in each group. All rats were given the relevant intervention once a day. At 12 weeks, sucrose preference and open field tests were performed to evaluate the anxiety and depression status of rats. In live rats, optical coherence tomography angiography was used to measure retinal thickness and blood flow, while electroretinograms (ERGs) and visual evoked potentials (VEPs) were used to evaluate retinal function. The next day, the specimens were sacrificed for serological, histological, immunofluorescence, Western blot and transmission electron microscopy examinations to explore the mechanism of MMXY in CUMS rats. Results: MMXY improved the anxiety and depression-like behavior of rats. Results of optical coherence tomography angiography showed that MMXY improved retinal inner thickness and blood flow in CUMS rats. MMXY improved the amplitude of a- and b-waves in the scotopic and photopic ERG, as well as N2 and P2 peak time and amplitude in the flash-VEP in CUMS rats. Retinal histological staining and transmission electron microscopy showed that MMXY reversed retinal morphology and ultrastructure in CUMS rats. MMXY reduced the expression of Beclin1 and LC3I/II proteins, regulated the PI3K/Akt/mTOR pathway, inhibited autophagy, and had a protective effect on the retina in CUMS rats. Conclusion: MMXY may effectively improve retinal morphology and function as well as anxiety and depression-like behaviors in CUMS rats by regulating the PI3K/Akt/mTOR signaling pathway.

Evaluation of an Ussing Chamber System Equipped with Rat Intestinal Tissues to Predict Intestinal Absorption and Metabolism in Humans.

BACKGROUND AND OBJECTIVE: Oral bioavailability (F) is one of the key factors that need to be determined in drug discovery. This factor is determined by the permeability and solubility of new molecule entities (NMEs) according to the biopharmaceutics classification system (BCS). METHODS: In the present study, we evaluated the permeability of 22 drugs in rat intestinal tissues using an Ussing chamber system and correlated the permeability with data on human intestinal absorption (Fa) and intestinal availability (Fa × Fg) reported in the literature. RESULTS: The rat intestinal permeability data were better correlated with the combined effect of the absorbed fraction (Fa) and the fraction escaping intestinal metabolism (Fg) than Fa itself. Clear regional dependent absorption was observed for most of the test drugs, and ileal Papp was generally higher than that in other segments. Finally, the function of the efflux transporter P-glycoprotein (P-gp) with regard to oral absorption of substrates was evaluated with an Ussing chamber. We also demonstrated that the rat intestinal stability of the three cytochrome P450 (CYP) substrates was consistent with the human data. CONCLUSION: An Ussing chamber system incorporating rat intestinal tissue would be a valuable tool to predict human intestinal absorption and metabolism for molecules with various physicochemical properties.

Quality evaluation of Tetrastigma hemsleyanum different parts based on quantitative analysis of 42 bioactive constituents combined with multivariate statistical analysis.

INTRODUCTION: The root of Tetrastigma hemsleyanum (RTH) has been widely used as a folk medicine in China. Meanwhile, its stems (STH) and leaves (LTH) are consumed as functional tea and food supplementation. Therefore, it is important to get a better understanding of the distribution of bioactive constituents in different parts of T. hemsleyanum. OBJECTIVE: To develop a method for quantitative analysis of multiple bioactive constituents and comparing their distribution in RTH, STH and LTH. METHODS: Ultra-performance liquid chromatography triple quadrupole ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) was used for the quantitative analysis. The quantitative data were further analysed by principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least squares determinant analysis (PLS-DA). RESULTS: Forty-two constituents in RTH, STH and LTH, including 14 flavonoids, three phenolic acids, 15 amino acids and 10 nucleosides, were quantitatively determined. The contents of flavonoids and phenolic acids in LTH were significantly higher than those in RTH and STH. While the contents of amino acids and nucleosides in LTH were less than those in RTH and STH. Multivariate statistical analysis can significantly classify and distinguish RTH, STH, and LTH. CONCLUSIONS: The present method would be helpful for the quality control of T. hemsleyanum, and the results would be useful for the efficient utilisation of T. hemsleyanum in the future.