Objective:To investigate the protective effects of p53/glucose transporter 4 (GLUT4) regulation on cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation.Methods:Human myocardial AC16 cells were treated with 33 mmol/L glucose and a hypoxic chamber to establish an in vitro model of high glucose combined with hypoxia/reoxygenation. Based on the glucose concentration in the medium and hypoxia/reoxygenation conditions, AC16 cells were divided into control group, high glucose group, hypoxia/reoxygenation group and high glucose combined with hypoxia/reoxygenation group. On the basis of high glucose combined with hypoxia/reoxygenation group, cells were transfected with empty vector, p53 small interfering RNA (siRNA), and co-transfected with p53 and GLUT4 siRNA to establish negative control group, sip53 transfection group, and sip53+siGLUT4 transfection group, respectively. Western blotting was used to detect the levels of hypoxia-inducible factor-1α (HIF-1α), p53, GLUT4, dynamin-related protein 1 (Drp1), mitofusin 2 (Mfn2), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartic acid specific protease-3 (Caspase-3). The levels of reactive oxygen species were detected using the 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe. Mitochondria were labeled with the Mito-Tracker Deep Red FM fluorescent probe to assess mitochondrial morphology and their related parameters. Mitochondrial membrance potential was meausred using the JC-1 detection kit. Adenosine triphosphate (ATP) content was determined using an ATP assay kit. Glucose uptake ability was evaluated by measuring the fluorescence intensity of 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy- D-glucose (2-NBDG) using a multifunctional microplate reader. Apoptosis was assessed by TUNEL assay. Results:The relative expression of HIF-1α protein in the high glucose combined with hypoxia/reoxygenation group was 1.189±0.185, higher than that in the control group (0.086±0.071) ( P<0.05). The relative expression of p53 protein in the high glucose combined with hypoxia/reoxygenation group was 1.248±0.194, higher than those in the control group (0.730±0.184), high glucose group (0.932±0.161) and hypoxia/reoxygenation group (1.109±0.151) (all P<0.05). The relative expression of GLUT4 protein in the high glucose combined with hypoxia/reoxygenation group was 0.407±0.140, lower than those in the control group (1.061±0.060) and hypoxia/reoxygenation group (0.781±0.092) (both P<0.05). The fluorescence intensity of reactive oxygen species in the high glucose combined with hypoxia/reoxygenation group was 38.31±1.66, higher than that in the control group (11.59±1.02) ( P<0.05). The number of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (62.00±15.26), lower than those in the control group (136.20±23.55) and high glucose group (96.55±13.72) (both P<0.05). The average mitochondrial area in the high glucose combined with hypoxia/reoxygenation group was (7.02±1.38) μm 2, lower than those in the control group [(13.74±0.67) μm 2], high glucose group [(9.27±1.99) μm 2] and hypoxia/reoxygenation group [(9.64±2.36) μm 2] (all P<0.05). The average perimeter of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (9.10±1.14) μm, lower than those in the control group [(13.35±0.69) μm] and the hypoxia/reoxygenation group [(10.83±1.58) μm] (all P<0.05). The number of mitochondrial branches was 53.73±9.49, lower than those in the control group (147.10±25.99), high glucose group (97.08±13.65) and hypoxia/reoxygenation group (104.80±24.92) (all P<0.05). The average branch length of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (1.45±0.26) μm, lower than that in the control group [(2.29±0.52) μm] ( P<0.05). The red-green fluorescence intensity ratio in the high glucose combined with hypoxia/reoxygenation group was 0.580±0.133, lower than those in the control group (2.379±0.242), high glucose group (1.200±0.112) and hypoxia/reoxygenation group (0.883±0.076) (all P<0.05). The ATP content of the high glucose combined with hypoxia/ reoxygenation group was (0.025±0.003) μmol/10 5 cells, lower than those of the control group [(0.137±0.012) μmol/10 5 cells], high glucose group [(0.078±0.003) μmol/10 5 cells] and hypoxia/reoxygenation group [(0.073±0.010) μmol/10 5 cells] (all P<0.05). The fluorescence intensity of 2-NBDG in the high glucose combined with hypoxia/reoxygenation group was 257 315±7 951, lower than those in the control group (339 597±10 165), high glucose group (317 293±8 876) and hypoxia/reoxygenation group (314 611±12 228) (all P<0.05). The relative expression of Drp1 protein in high glucose combined with hypoxia/reoxygenation group was 1.203±0.090, higher than those in the control group (0.705±0.170), high glucose group (0.910±0.106) and hypoxia/reoxygenation group (1.002±0.112) (all P<0.05). The relative expression of Mfn2 protein in the high glucose combined with hypoxia/reoxygenation group was 0.706±0.285, lower than those in the control group (1.988±0.139), high glucose group (1.305±0.076) and hypoxia/reoxygenation group (1.131±0.236) (all P<0.05). The relative expression levels of Bax/Bcl-2 and Caspase-3 proteins in the high glucose combined with hypoxia/reoxygenation group were 2.318±0.216 and 1.076±0.076, respectively, higher than those in the control group (0.281±0.046 and 0.442±0.084), high glucose group (0.673±0.043 and 0.662±0.159) and hypoxia/reoxygenation group (0.807±0.293 and 0.835±0.058), respectively (all P<0.05). The TUNEL fluorescence intensity of the high glucose combined with hypoxia/reoxygenation group was 70.55±7.22, higher than those of the control group (14.10±5.93), high glucose group (36.59±2.56) and hypoxia/reoxygenation group (39.04±6.016) (all P<0.05). The relative expression levels of p53 protein in the sip53 transfection group and sip53+siGLUT4 transfection group were 0.322±0.147 and 0.391±0.149, respectively, lower than that in the high glucose combined with negative control group (1.002±0.035) (both P<0.05). The relative expression of GLUT4 protein in the sip53 transfection group was 1.871±0.123, higher than that in the negative control group (1.281±0.232) ( P<0.05). The relative expression of GLUT4 protein in the sip53+siGLUT4 transfection group (0.951±0.193) was lower than that in the sip53 transfection group ( P<0.05). The fluorescence intensity of reactive oxygen species in the sip53 transfection group (27.73±0.74) was lower than that in the negative control group (38.83±0.83) ( P<0.05). The fluorescence intensity of reactive oxygen species in the sip53+siGLUT4 transfection group (43.12±5.08) was higher than that in the sip53 transfection group ( P<0.05). The number of mitochondria, the average area of mitochondria, the average perimeter of mitochondria, the number of mitochondrial branches and the average branch length of mitochondria in the sip53 transfection group were (92.27±10.10), (9.25±0.42) μm 2, (10.86±0.58) μm, (83.27±13.57), and (1.81±0.21) μm, respectively. They were higher than (52.36±16.87), (7.44±1.49) μm 2, (9.22±1.11) μm, (52.36±16.87), and (1.22±0.26) μm in the negative control group (all P<0.05). The number of mitochondria, the average area of mitochondria, the average perimeter of mitochondria, the number of mitochondrial branches and the average branch length of mitochondria in the sip53+siGLUT4 transfection group were (53.73±9.49), (6.89±0.61) μm 2, (8.88±0.47) μm, (53.73±9.49), and (1.22±0.17) μm, respectively, lower than those in the sip53 transfection group (all P<0.05). The red-green fluorescence intensity ratio, ATP content, 2-NBDG fluorescence intensity and relative expression of Mfn2 protein in the sip53 transfection group were 1.27±0.23, (0.048±0.021) μmol/10 5 cells, 275 923±10 447 and 2.608±0.581, respectively, higher than those in the negative control group [0.53±0.21, (0.020±0.007) μmol/10 5 cells, 254 875±8 078, and 0.687±0.146, respectively] (all P<0.05). The red-green fluorescence intensity ratio, ATP content, 2-NBDG fluorescence intensity and relative expression of Mfn2 protein in the sip53+siGLUT4 transfection group were 0.40±0.08, (0.011±0.012) μmol/10 5 cells, 199 511±6 855, and 0.649±0.070, respectively, lower than those in the sip53 transfection group (all P<0.05). The relative expression levels of Drp1, Bax/Bcl-2, Caspase-3 proteins and TUNEL fluorescence intensity in the sip53 transfection group were 0.759±0.063, 0.446±0.161, 1.048±0.300, and 48.93±1.48 respectively, lower than those (1.065±0.149, 1.197±0.133, 1.847±0.201, and 67.61±9.99) in the negative control group (all P<0.05). The relative expression levels of Drp1, Bax/Bcl-2, Caspase-3 proteins and TUNEL fluorescence intensity in the sip53+siGLUT4 transfection group were 0.958±0.166, 2.660±0.135, 1.587±0.220, and 63.39±12.84, respectively, higher than those in the sip53 transfection group (all P<0.05). Conclusions:Under the condition of high glucose combined with hypoxia/reoxygenation, p53 induces cardiomyocyte injury by down-regulating GLUT4. Inhibition of p53 can increase the expression of GLUT4, thereby reducing cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation.

Objective To analyze the law of acupoint selection and compatibility of acupuncture and moxibustion and the application law of acupuncture and moxibustion in the treatment of lactational mastitis using complex network technology.Methods The clinical research literature about acupuncture and moxibustion treatment of lactational mastitis was retrieved from CNKI,CBM,Wanfang Data,VIP and PubMed from the establishment of the databases to March 15,2025.The literature was screened according to the standards to build a prescription database of acupuncture and moxibustion treatment of lactational mastitis.SPSS Modeler 18.0 software was used to analyze association rules,and Gephi 0.9 software was used for complex network analysis.Results A total of 108 articles were included.141 acupuncture and moxibustion prescriptions were extracted,involving 74 acupoints,with a total use frequency of 677 times.The high-frequency acupoints were Jianjing,Danzhong,Rugen,Zusanli,Neiguan,etc.Specific acupoints were mainly composed of Wushu acupoints(169 times,21.10%);the acupoints were mainly distributed in the limbs(36);the most frequently used meridian was stomach meridian(168 times,24.82%).The combination of acupoints with the highest correlation was Jianjing-Neiguan-Rugen.Complex network analysis identified 22 core acupoints,with the most commonly used acupuncture method being filiform needle acupuncture(79 times).Conclusion Acupuncture and moxibustion treatment of lactational mastitis pays special attention to the selection of stomach meridian.The compatibility mode is mainly from top to bottom,and the corresponding acupoints are selected according to syndrome differentiation.

Aim To explore the mechanism of Epimedii folium-Astmgali radix activating the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way and its effect on sperm production and vitality in oligoasthenospermia.Methods Sixty male SD rats were used to establish a model of oligoasthenospermia with cyclophosphamide.They were randomly divided into six groups:experimental group(further divided into high,medium,and low dose group),model group,control group and blank group.The oligoasthenosper-mia model was established by using cyclophosphamide in experimental group,levocarnitine group and model group.The rats in the high,medium,and low dose group of the experimental group were orally adminis-tered Epimedii folium-Astmgali radix extract at doses of 800,400,and 200 mg·kg-1,respectively,Once daily for 35 days.Rats of the control group were orally ad-ministered 250 mg·kg-1·d-1 of levocarnitine,Once daily for 35 days.ELISA was used to detect serum of T,E2,FSH,and LH.Western blot and IHC staining were used to detect the expression of SCF,c-kit,Bcl-2,Bax,PI3K,and Akt proteins in rat testicular tissues.Sperm activity is examined by microscopy.The testicu-lar tissue structure and cell morphology of rats in each group were observed.Results Compared with the model group,Epimedii folium-Astmgali radix increased the sperm density,total viability rate,and vitality(P＜0.05,P＜0.01),decreased sperm apoptosis rate and LH,T,and E2 levels(P＜0.05,P＜0.01),decreased Bax protein expression in testicular tissue(P＜0.01),and increased Bcl-2,SCF,c-Kit,PI3K,and Akt protein expression(P＜0.05,P＜0.01);it increased the number of germ cells,thickened basement membrane,and significantly improved seminiferous tubule mor-phology,even showing germ cells at different develop-mental stages and mature sperm.Conclusions Epi-medii folium-Astmgali radix has a significant therapeu-tic effect on oligoasthenospermia in rats.Its mechanism may be related to the activation of the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way promoting the proliferation and differentiation of germ cells,and promoting sperm production,maturation and motility.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective To establish a method for simultaneous determination of four high-molecular-weight thiol derivatives (TDs) in workplace air by gas chromatography. Methods The four kinds of vapor-phase macromolecular TDs (1-pentanethiol, 1-hexanethiol, 1-benzyl mercaptan, and n-octanethiol) in the workplace air were collected using the GDH-1 air sampling tubes, desorbed with anhydrous ethanol, separated on a DB-FFAP capillary column, and determined by flame ionization detector. Results The quantitation range of the four TDs was 0.30-207.37 mg/L, with the correlation coefficients greater than 0.999 00. The minimum detection mass concentrations and minimum quantitation mass concentrations were 0.18-0.32 and 0.60-1.05 mg/m³, respectively (both calculated based on the 1.5 L sample and 3.0 mL desorption solvent). The mean desorption efficiencies ranged from 87.07% to 103.59%. The within-run and between-run relative standard deviations were 1.92%-8.22% and 1.89%-8.45%, respectively. The samples can be stored at room temperature or 4 ℃ for three days and up to 7 days at -18 ℃. Conclusion This method is suitable for the simultaneous determination of four vapor-phase TDs in workplace air.

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.