Aim To investigate the effects of dimethyl-arginine dimethylamino hydrolase 1(DDAH1)on high glucose-induced mitochondrial dysfunction and mitoph-agy in vascular endothelial cells.Methods JC-1 stai-ning was used to detect mitochondrial membrane poten-tial.DCFH-DA fluorescent probe was employed to measure reactive oxygen species(ROS)levels.Ho-echst staining was used to assess cell apoptosis.Real-time PCR was conducted to detect DDAH1 mRNA lev-els.Western blot was performed to analyze the expres-sion of DDAH1,LC3-Ⅰ and LC3-Ⅱ proteins.Mitochon-drial probe Mitotracker and autophagosome marker pro-tein LC3 were used in cell immunofluorescence co-lo-calization to assess mitochondrial autophagy,and high-performance liquid chromatography was utilized to measure the levels of asymmetric dimethylarginine(ADMA)in cell supernatant.Results High glucose treatment for 48 h significantly reduced mitochondrial membrane potential,increased ROS production,and promoted apoptosis in human umbilical vein endothelial cells(HUVECs).High glucose downregulated the ex-pression of LC3-Ⅱ/LC3-Ⅰ proteins,reduced the co-lo-calization of Mitotracker and LC3,and inhibited mito-chondrial autophagy.Autophagy inhibitors 3-MA or CQ exacerbated high glucose-induced mitochondrial dam-age and apoptosis in HUVECs,while autophagy activa-tor RAPA alleviated these effects.High glucose signifi-cantly downregulated DDAH1 protein expression in HUVECs and increased ADMA levels in cell superna-tant.DDAH1 siRNA inhibited mitochondrial autoph-agy,reduced mitochondrial membrane potential,and promoted apoptosis,whereas DDAH1 overexpression enhanced mitochondrial autophagy and alleviated high glucose-induced apoptosis in HUVECs.Conclusion High glucose-induced endothelial mitochondrial dys-function is associated with the suppression of DDAH1 expression,the increase of ADMA levels,and thereduc-tion of mitochondrial autophagy.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective To analyze the influencing factors for postoperative anastomotic leak (AL) in carcinoma of the esophagus and gastroesophageal junction and construct a nomogram predictive model. Methods The patients who underwent radical esophagectomy at Jinling Hospital Affiliated to Nanjing University School of Medicine from January 2018 to June 2020 were included in this study. Relevant variables were screened using univariate and multivariate logistic regression analyses. A nomogram was then developed to predict the risk factors associated with postoperative AL. The predictive performance of the nomogram was validated using the receiver operating characteristic (ROC) curve. Results A total of 468 patients with carcinoma of the esophagus and gastroesophageal junction were included in the study, comprising 354 males and 114 females, with a mean age of (62.8±7.2) years. The tumors were predominantly located in the middle or lower esophagus, and 51 (10.90%) patients experienced postoperative AL. Univariate logistic regression analysis indicated that age, body mass index (BMI), tumor location, preoperative albumin levels, diabetes mellitus, anastomosis technique, anastomosis site, and C-reactive protein (CRP) levels were potentially associated with AL (P<0.05). Multivariate logistic regression analysis identified age, BMI, tumor location, diabetes mellitus, anastomosis technique, and CRP levels as independent risk factors for AL (P<0.05). A nomogram was developed based on the findings from the multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was 0.803, indicating a strong concordance between the actual observations and the predicted outcomes. Furthermore, decision curve analysis demonstrated that the newly established nomogram holds significant value for clinical decision-making. Conclusion The predictive model for postoperative AL in patients with carcinoma of the esophagus and gastroesophageal junction demonstrates strong predictive validity and is essential for guiding clinical monitoring, early detection, and preventive strategies.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Rheumatoid arthritis(RA)is a chronic autoimmune disease of unknown etiology that can cause joint destruction and deformity.As a small molecule cytokine,the chemokine C-X-C motif chemokine ligand 12(CXCL12)regulates the pathogenesis of rheumatoid arthritis by binding to the specific receptor CXC chemokine receptor 4(CXCR4).Therefore,based on the bio-logical characteristics of CXCL12 and CXCR4,this paper intro-duces the pathogenesis of CXCL12/CXCR4 in RA and summari-zes the progress in RA-related research,with the aim of providing clinical value for understanding the pathogenesis of RA and de-veloping novel therapeutic targets.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Diabetic encephalopathy(DE)is a complication of the central nervous system induced by diabetes,characterized by insidious onset and complex pathological mechanisms.Recent research has revealed that the pathological mechanisms of DE are closely associated with the imbalance of intercellular communica-tion across multiple organs.Exosomes,serving as vital media-tors of intercellular communication,are involved in the patholog-ical progression of DE and hold promise as diagnostic biomarkers and therapeutic targets for DE.Traditional Chinese medicine(TCM)can improve communication between brain cells and be-tween peripheral and brain tissues by regulating exosomes and their contents,thereby preventing and treating DE.Meanwhile,exosomes,as targeted delivery carriers of active molecules,can carry TCM monomers more easily across the blood-brain barrier to prevent and treat DE.In light of this,this review summarizes the regulatory role of exosomes in the pathological progression of DE and explores the enormous potential of TCM in the preven-tion and treatment of DE by regulating exosomes and using exo-somes as traditional Chinese medicine carriers,aiming to pro-vide new evidence for the prevention and treatment of DE with TCM.

This study aims to explore the role and mechanism of berberine in promoting the expression of aquaporin 4(AQP4) in astrocytes by regulating the expression of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance(IR). The IR-HepG2 cell model was established with 1×10~(-6) mol·L~(-1) insulin. With metformin as the positive control, the safe concentrations of berberine and metformin were screened by cell counting kit-8(CCK-8) and lactate dehydrogenase(LDH) leakage assays, and the effect of berberine on the IR of HepG2 cells was evaluated by glucose consumption. NanoSight was used to measure the particle size and concentration of exosomes secreted by HepG2 cells in each group. HepG2 cell-derived exosomes in each group were incubated with astrocytes for 24 h, and the protein and mRNA levels of AQP4 in HA1800 cells were determined by Western blot and qRT-PCR, respectively. qRT-PCR was performed to determine the expression of miR-383-5p in HepG2 cell-derived exosomes and HA1800 cells after co-incubation. Western blotting was employed to determine the expression levels of miRNAs and proteins associated with exosome production and release in HepG2 cells. The results showed that 10 μmol·L~(-1) berberine and 1 mmol·L~(-1) metformin significantly alleviated the IR of HepG2 cells and reduced the concentration of exosomes in HepG2 cells. The exosomes of HepG2 cells treated with berberine and metformin significantly up-regulated the protein and mRNA levels of AQP4 in HA1800 cells. The mRNA level of miR-383-5p in HepG2 cell exosomes and HA1800 cells co-incubated with berberine and metformin decreased significantly. The intervention with berberine and metformin significantly down-regulated the expression of proteins associated with the production of miRNAs(Dicer, Drosha) as well as the production(Alix, Vps4A) and release(Rab35, VAMP3) of exosomes in IR-HepG2 cells. In conclusion, berberine can promote the expression of AQP4 in astrocytes by inhibiting the production and release of miR-383-5p in HepG2-derived exosomes under IR.
Humans ; MicroRNAs/metabolism* ; Berberine/pharmacology* ; Hep G2 Cells ; Exosomes/genetics* ; Aquaporin 4/metabolism* ; Insulin Resistance ; Astrocytes/drug effects*

This study aims to observe the mind-tranquilizing effect of Fushen Decoction on mice and investigate its effects on the 5-hydroxytryptamine(5-HT) system and γ-aminobutyric acid(GABA) in the brain of the mouse model of 4-chloro-DL-phenylalanine(PCPA)-induced insomnia. ICR mice were administrated with coffee(1 g·kg~(-1)) for 3 days, and the effects of Fushen Decoction(10, 20, and 40 g·kg~(-1)) on the autonomic activities of normal mice and coffee-treated mice were observed. Furthermore, the effects of Fushen Decoction on the autonomic activity and sleep induced by a suprathreshold dose of pentobarbital sodium in the mouse model of PCPA(350 mg·kg~(-1) for 3 consecutive days)-induced insomnia were observed. The levels of tryptophan hydroxylase(TPH), 5-hydroxytryptophan(5-HTP), and 5-HT in the serum, as well as those of 5-HTP and 5-HT in the brain stem, hippocampus, and cortex, were measured by enzyme-linked immunosorbent assay(ELISA). The fluorescence intensity of 5-HT in the raphe nucleus, hippocampus, and cortex was measured by the immunofluorescence method. The protein levels of tryptophan hydroxylase-2(TPH2) and 5-HT_(1A) receptor(5-HT_(1A)R) in the brain stem, hippocampus, and cortex were measured by Western blot. The levels of GABA in the hypothalamus, hippocampus, and cortex were measured by ELISA and immunohistochemistry methods. The results showed that Fushen Decoction(20, 40 g·kg~(-1)) reduced the number of autonomous activities in normal mice, coffee-treated mice, and the mouse model of PCPA-induced insomnia, and prolonged the duration of sleep induced by a suprathreshold dose of pentobarbital sodium in the mouse model. Fushen Decoction(20, 40 g·kg~(-1)) elevated the levels of TPH, 5-HTP, and 5-HT in the serum, and TPH2, 5-HTP, 5-HT, and 5-HT_(1A)R in the brain stem, hippocampus, and cortex, and up-regulated GABA expression in the hypothalamus, cortex, and hippocampus of the mouse model of PCPA-induced insomnia. In conclusion, Fushen Decoction(20, 40 g·kg~(-1)) exerted a mind-tranquilizing effect on mice by up-regulating the expression of TPH2, enhancing the 5-HT system, and elevating the GABA level in the brain.
Animals ; Serotonin/genetics* ; Sleep Initiation and Maintenance Disorders/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Mice, Inbred ICR ; gamma-Aminobutyric Acid/genetics* ; Disease Models, Animal ; Fenclonine/adverse effects* ; Tryptophan Hydroxylase/genetics* ; Brain/metabolism* ; Sleep/drug effects* ; Humans ; 5-Hydroxytryptophan/metabolism*