OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

AIM:To compare and analyze the effectiveness and safety of reducing the diameter of the back optical zone diameter(BOZD)of orthokeratology lens designed by CRT and VST in controlling the progression of myopia in children and adolescents.METHODS:Retrospective study. The study subjects were 400 myopia patients aged 8-16 years who were admitted to the orthokeratology fitting center of our hospital from June 2019 to May 2022, with 400 eyes(including right eye data analysis). The subjects were divided into CRT-S group(BOZD<6.0 mm), CRT group(BOZD=6.0 mm), VST-S group(BOZD<6.2 mm), VST group(BOZD=6.2 mm)according to the brand of orthokeratology lens and BOZD group, with 100 cases in each group. Uncorrected visual acuity(UCVA), corneal flat K value, axial length, spherical equivalent, and incidence of corneal injury were collected and analyzed at 1 d, 1 wk, 1 and 6 mo, 1 and 2 a, respectively.RESULTS:After wearing lenses for 1 d, the UCVA of the VST-S group improved the fastest, but after 1 wk, all groups reached a good UCVA, and there was no significant difference between groups. The corneal flat K value of the CRT-S group decreased the most after wearing lenses for 6 mo, and there was no significant difference in the corneal flat K value of all groups after 1 year of lens wearing. At each time point, the axial length growth decreased significantly after reducing the BOZD of the same brand of orthokeratology lens. At 6 mo, there was no significant difference in the axial length growth and defocus ring diameter between the CRT-S group and the VST-S group, but at 1 and 2 a, the VST-S group had significantly lower axial length growth and defocus ring diameter than the CRT-S group. The growth of the diopter sphere and spherical equivalent(SE)was significantly reduced when the BOZD of the same brand of orthokeratology lens was reduced at 2 a follow-up. The VST-S group had the smallest changes in the degree of SE and had the best myopia control effect. There was no significant difference in the change value of the diopter cylinder and the incidence of corneal injury among the four groups.CONCLUSION:Reducing the BOZD of the orthokeratology lens can effectively control the growth of the axial length and the progression of myopia degree. The myopia control effect of the VST lens is better than that of the CRT lens after reducing the BOZD. Reducing the BOZD of the orthokeratology lens does not increase the risk of additional corneal injury.

AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

AIM:To compare and analyze the effectiveness and safety of reducing the diameter of the back optical zone diameter(BOZD)of orthokeratology lens designed by CRT and VST in controlling the progression of myopia in children and adolescents.METHODS:Retrospective study. The study subjects were 400 myopia patients aged 8-16 years who were admitted to the orthokeratology fitting center of our hospital from June 2019 to May 2022, with 400 eyes(including right eye data analysis). The subjects were divided into CRT-S group(BOZD<6.0 mm), CRT group(BOZD=6.0 mm), VST-S group(BOZD<6.2 mm), VST group(BOZD=6.2 mm)according to the brand of orthokeratology lens and BOZD group, with 100 cases in each group. Uncorrected visual acuity(UCVA), corneal flat K value, axial length, spherical equivalent, and incidence of corneal injury were collected and analyzed at 1 d, 1 wk, 1 and 6 mo, 1 and 2 a, respectively.RESULTS:After wearing lenses for 1 d, the UCVA of the VST-S group improved the fastest, but after 1 wk, all groups reached a good UCVA, and there was no significant difference between groups. The corneal flat K value of the CRT-S group decreased the most after wearing lenses for 6 mo, and there was no significant difference in the corneal flat K value of all groups after 1 year of lens wearing. At each time point, the axial length growth decreased significantly after reducing the BOZD of the same brand of orthokeratology lens. At 6 mo, there was no significant difference in the axial length growth and defocus ring diameter between the CRT-S group and the VST-S group, but at 1 and 2 a, the VST-S group had significantly lower axial length growth and defocus ring diameter than the CRT-S group. The growth of the diopter sphere and spherical equivalent(SE)was significantly reduced when the BOZD of the same brand of orthokeratology lens was reduced at 2 a follow-up. The VST-S group had the smallest changes in the degree of SE and had the best myopia control effect. There was no significant difference in the change value of the diopter cylinder and the incidence of corneal injury among the four groups.CONCLUSION:Reducing the BOZD of the orthokeratology lens can effectively control the growth of the axial length and the progression of myopia degree. The myopia control effect of the VST lens is better than that of the CRT lens after reducing the BOZD. Reducing the BOZD of the orthokeratology lens does not increase the risk of additional corneal injury.

Lactate, with a chemical formula of C₃H₆O₃, is an intermediate product of glucose metabolism in the body and a raw material for hepatic gluconeogenesis. Under physiological resting conditions, the body mainly relies on aerobic oxidation of sugar and fat for energy supply, so the blood lactate concentration is lower. However, during exercise, the enhanced glycolysis in skeletal muscles leads to the significant release of lactate into the bloodstream, causing a marked increase in blood lactate concentration. Traditionally, lactate has been regarded as a metabolic waste product of glycolysis and a contributor to exercise-induced fatigue. Nevertheless, recent studies have revealed that, in humans, lactate is a major vehicle for carbohydrate carbon distribution and metabolism, serving not only as an energy substance alongside glucose but also as a vital component in various biological pathways involved in cardiac energetics, muscle adaptation, brain function, growth and development, and inflammation therapy. Two primary pathways can elevate lactate levels in neurons during exercise. One is peripheral skeletal muscle-derived lactate, which can enter the bloodstream and cross the blood-brain barrier into the brain with the assistance of monocarboxylate transporters (MCTs) from the solute carrier family 16 (SLC16). The other is the central brain-derived pathway. During exercise, neuronal activity is enhanced, promoting the secretion of neuroactive substances such as glutamate, norepinephrine, and serotonin in the brain. This activates astrocytes to break down glycogen into lactate and stimulates glutamate from the presynaptic terminal into the synaptic cleft. It upregulates the glucose transport protein-1 (GLUT-1) expression, allowing astrocytes to convert glucose into lactate through glycolysis. The lactate is produced via peripheral pathways and central pathways during exercise are transported by astrocyte membrane monocarboxylate transporters MCT1 and MCT4 to the extracellular space, where neurons take it up through neuronal cell membrane MCT2. The lactate in neurons can serve as an alternative energy source of glucose for neuronal functional activities, meeting the increased energy demands of synaptic activity during exercise, and maintaining energy balance and normal physiological function in the brain. Additionally, acting as a signaling molecule lactate can enhance synaptic plasticity through the SIRT1/PGC-1α/FNDC5 and ERK1/2 signaling pathways, lactate can promote angiogenesis by upregulating VEGF-A expression through the PI3K/Akt and ERK1/2 signaling pathways, stimulate neurogenesis via the Akt/PKB signaling pathway, and reduce neuroinflammation through activation of the “lactate timer”. Overall, lactate contributes to the protection of neurons, the promotion of learning and memory, the enhancement of synaptic plasticity, and the reduction of neuroinflammation in the nervous system. While lactate may serve as a potential mediator for information exchange between the peripheral and central nervous systems during exercise, further experimental research is needed to elucidate its action mechanisms in the nervous system. In addition, future studies should utilize advanced neurophysiological and molecular biology techniques to uncover the importance of lactate in maintaining brain function and preventing neurological diseases. Accordingly, this article first reviews the historical research on lactate, then summarizes the metabolic characteristics and neuronal sources of lactate, and finally explores the role and mechanisms of exercise-induced lactate in the nervous system, aiming to provide new perspectives and targets for understanding the mechanisms underlying exercise promotion of brain health.

ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

ObjectiveTo systematically analyze the global policy framework, standard systems and application technology models of digital rehabilitation within the framework of the World Health Organization (WHO) Global Digital Health Strategy and propose policy recommendations for the future development of digital rehabilitation. MethodsBased on the policies on digital health and rehabilitation development issued by the WHO, focusing on the Global Digital Health Strategy, Rehabilitation 2030 Initiative, Rehabilitation in Health Systems, Rehabilitation in Health Systems: A Guide for Action, and World Report on Disability, a systematic review was conducted, to explore the policy architecture and core content of digital rehabilitation, the standard system for digitalizing rehabilitation, and key technological models for the development of digital rehabilitation. ResultsIn the context of global health and digital transformation, the development of digital rehabilitation services was an essential component of the global digital health strategy. Building a comprehensive policy framework and content system for digital rehabilitation was critical for strengthening rehabilitation data governance, enhancing data utilization efficiency, and ensuring data privacy and security. Empowering rehabilitation with digital technology was vital for improving the standardization, effectiveness, coverage, quality and safety of rehabilitation services. International digital rehabilitation policies primarily involved the following areas: policy and governance, digital standard systems, data privacy, security and ethics, digital talent cultivation and capacity building, and monitoring, evaluation and continuous improvement of digitally empowered rehabilitation services. The standard system for rehabilitation digitization covered the three major reference classifications of the WHO Family of International Classifications, including International Classification of Diseases Eleventh Revision (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI), especially ICF. It also included international data interoperability standards, data security and privacy protection standards, data quality and certification standards, and health information standards, etc. The application technology models of digital rehabilitation primarily included data-driven service models, artificial intelligence -enabled models, and remote rehabilitation models combined with virtual reality, augmented reality technologies, and Internet of Things support. ConclusionThe establishment and implementation of comprehensive policies, standards and technological models for digital rehabilitation are crucial for driving the digital transformation and development of global rehabilitation services. Under the framework of the WHO Global Digital Health Strategy, it is necessary to build adaptive digital rehabilitation policy frameworks, and enhance digital governance capabilities and levels, establishing and improving digital rehabilitation standard systems, and promoting the interoperability and integration of rehabilitation data with other health big data. Meanwhile, it is essential to actively develop data-driven technological models for rehabilitation services to comprehensively improve the accessibility, availability, quality and safety of rehabilitation services.

OBJECTIVE To study the effects of Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells. METHODS The rats were given Sanchong tongluo sanjie formula powder [0.946 g/（kg·d）]， Sanchong tongluo sanjie formula decoction [2.730 g/（kg·d）]， and normal saline intragastrically， and injected with Cisplatin injection （4.2 mg/kg） intra-peritoneally to prepare powder-containing serum， decoction-containing serum， positive control serum and negative control serum. Lewis lung cancer cells were divided into negative control serum group， positive control serum group， and 5%， 10%， 20% drug-containing serum groups. The cell proliferation inhibition rates at 24， 48， and 72 hours post- intervention were measured to screen the optimal intervention concentrations of powder-containing serum and decoction-containing serum. The cell invasion ability， metastasis ability and apoptotic rate were detected in the negative control serum group， positive control serum group， 20% powder-containing serum group， and 20% decoction-containing serum group. Protein expressions of vascular endothelial growth factor （VEGF）， hypoxia-inducible factor-1α （HIF-1α）， prolyl hydroxylase-2 （PHD2）， matrix metalloproteinase-2 （MMP-2）， extracellular regulated protein kinases （ERK），c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK） were detected. RESULTS The cell proliferation inhibition rates for both the 20% powder-containing serum group and the 20% decoction-containing serum group， when intervened for 48 hours， were not less than 50%. Compared with negative control serum group， the number of invasive Lewis lung cancer cells and migration distance were decreased significantly， while the apoptotic rate was increased significantly （P＜0.05）； the apoptotic rate in the 20% powder- containing serum group was significantly higher than 20% decoction-containing serum group （P＜0.05）. The protein expressions of PHD2 and p38 MAPK were increased significantly in the 20% powder-containing serum group （P＜0.05）， while the protein expression of HIF-1α was decreased significantly in the 20% decoction-containing serum group （P＜0.05）. CONCLUSIONS Sanchong tongluo sanjie formula can inhibit the proliferation， invasion and metastasis of Lewis lung cancer cells while promoting their apoptosis. The mechanism of action may be related to regulating the PHD2/HIF-1α signaling pathway. Furthermore， the powder demonstrates superior efficacy compared to the decoction， suggesting that they may possess different mechanisms of action.

The Hazardous Drug Exposure Management: Information for Healthcare Settings (2023 Edition) released by the National Institute for Occupational Safety and Health (NIOSH) of US provided detailed protection recommendations for medical personnel to mitigate the risks of occupational exposure to hazardous drugs. This study reviewed the literature in terms of hazard identification, occupational exposure assessment, risk assessment, risk management planning, and waste and spill control. It also explored the precautions for each step of hazardous drug handling, aiming to raise medical personnel's awareness of hazardous drug protection and improve their self-protection skills. The findings provided valuable references for medical institutions to develop hazardous drug disposal plans and reduce employees' exposure to hazardous drugs and occupational injuries.