ObjectiveTo elucidate the effects of autonomic neuromodulators [calcium chloride (CaCl₂)-acetylcholine (ACh)] on atrial electrical remodeling and histopathological changes in rats, thereby providing evidence for further investigation into the pathological mechanisms by which autonomic imbalance induces atrial fibrillation (AF). MethodsTen 8-week-old male Sprague-Dawley (SD) rats were randomly divided into experimental and control groups, with 5 rats in each group. The experimental group received daily tail vein injections of a CaCl₂-ACh mixed solution for 28 days, while the control group received an equal volume of saline. Surface electrocardiograms were recorded before and after daily administration. On day 28 of administration, under isoflurane inhalation anesthesia, echocardiography was performed, and then the rats were euthanized by exsanguination under isoflurane anesthesia for tissue collection. Body weight and heart weight of rats were measured, and electrophysiological parameters including AF inducibility, conduction velocity, and conduction dispersion in isolated rat hearts were monitored using the MappingLab multichannel electrophysiological mapping system. HE staining was performed to evaluate atrial tissue architecture and inflammatory cell infiltration. The expression levels of matrix metalloproteinase 9 (MMP-9) and interleukin-1 beta (IL-1β) were analyzed by Western blotting. Masson staining was used to quantitatively analyze the proportional distribution of collagen fibers and myocardial fibers, and to calculate the area of collagen deposition, thereby evaluating the degree of myocardial fibrosis. Wheat germ agglutinin (WGA) staining was used to evaluate morphological changes of cardiomyocytes. Dihydroethidium (DHE) staining was used to detect the level of oxidative stress in atrial myocytes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect atrial cell apoptosis. ResultsCompared with the control group, the experimental group showed obvious arrhythmias on electrocardiograms. Echocardiography after 28 days of administration revealed significant structural remodeling in the experimental group, with a marked increase in left atrial anteroposterior diameter (P < 0.05), and also showed cardiac dysfunction, with significant decreases in left ventricular ejection fraction and left ventricular fractional shortening (P < 0.01). Compared with the control group, the experimental group showed a significantly increased heart weight-to-body weight ratio (P < 0.05), a markedly higher AF inducibility (P < 0.001), a significantly slowed atrial conduction velocity (P < 0.05), an uneven isochronal map with irregular directions, and a significantly increased conduction dispersion (P < 0.01). HE staining showed that atrial myocytes in the experimental group were disorganized, with slight inflammatory cell infiltration. Western blotting showed that the expression levels of MMP-9 and IL-1β in the atrial tissue of the experimental group were significantly upregulated (P < 0.05). Masson staining showed a significant increase in collagen deposition and a significant increase in fibrosis area in the atrial tissue of the experimental group (P < 0.001). WGA staining showed that cardiomyocytes in the experimental group were significantly hypertrophied compared with the control group (P < 0.05). DHE staining and TUNEL staining revealed that the level of oxidative stress in atrial myocytes (P < 0.001) and the apoptotic rate (P < 0.01) were both significantly increased. Conclusion Daily tail vein injections of the autonomic neuromodulator CaCl₂-ACh mixed solution for 28 days can successfully induce AF in rats, accompanied by significant atrial structural remodeling, electrical remodeling, and oxidative stress.

Objective To explore the value of shear wave elastography(SWE)combined with carbohydrate antigen 15-3(CA15-3)in differentiating benign and malignant breast imaging and reporting data system(BI-RADS)category 4 breast masses.Methods Ninety patients with breast tumors confirmed by surgical pathology at the Affiliated Hospital of Yunnan University from December 2021 to June 2024 were enrolled,all with BI-RADS category 4 breast masses.The patients were divided into a benign group(n=42)and a malignant group(n=48)according to whether the breast masses were benign or malignant.All of them underwent SWE examination,and serum CA15-3 levels were determined using electrochemiluminescence method.Serum CA15-3 levels and SWE parameters[elasticity standard deviation(ESD),mean elasticity value(Emean),maximum elasticity value(Emax)and the ratio of breast mass elasticity to same-layer low fat elasticity(Eratio)]were compared between the two groups.The area under the receiver operating characteristic curve(AUC)was used to evaluate the diagnostic performance of serum CA15-3 levels,SWE parameters,and their combination for benign and malignant BI-RADS category 4 breast masses.Results The SWE parameters(ESD,Emean,Emax,and Eratio)and serum CA15-3 levels in the malignant group were significantly higher than those in the benign group(P<0.05).The AUC values of ESD,Emean,Emax,Eratio,and serum CA15-3 levels for the diagnosis of benign and malignant BI-RADS category 4 breast masses were 0.718(95%CI:0.613-0.824),0.791(95%CI:0.701-0.881),0.721(95%CI:0.615-0.826),0.721(95%CI:0.613-0.830)and 0.793(95%CI:0.702-0.885),respectively.Notably,SWE parameters combined with serum CA15-3 levels achieved an AUC value of 0.953(95%CI:0.917-0.992).Conclusion The combination of CA15-3 and SWE exhibits high efficiency in diagnosing the benign and malignant nature of BI-RADS category 4 breast masses.

BACKGROUND:During healing process of chronic wounds,excessive production of reactive oxygen species can impair the function of L929 fibroblasts,thereby delaying wound repair.Therefore,protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE:To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma(CMC-OCS/PRP)hydrogel on L929 cells under H2O2 stimulation. METHODS:CMC-OCS/PRP hydrogels were prepared,and the micromorphology,degradation performance,scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized.L929 cells with good growth state were taken and cultured in five groups.The control group was cultured conventionally.H2O2 was added to the H2O2 group.Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract+H2O2 was added to the CMC-OCS group.Platelet-rich plasma gel extract+H2O2 was added to the PRP group.The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract+H2O2.Each group was treated with hydrogel extract for 6 hours,and then H2O2 for 24 hours.After culture,the levels of active oxygen and malondialdehyde,apoptosis and expression of collagen fiber I protein were detected.In the presence of H2O2,the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours,respectively.Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION:(1)CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability,could effectively remove H2O2 and hydroxyl radicals in vitro,and had good biocompatibility.(2)Compared with the control group,the apoptosis rate,reactive oxygen species,and malondialdehyde levels were increased(P<0.05);the spread area of cells was decreased(P<0.05),and the expression of collagen fiber I protein had no significant changes(P>0.05)in the H2O2 group.Compared with the H2O2 group,reactive oxygen species level was decreased in the CMC-OCS group(P<0.05),malondialdehyde level was decreased(P<0.05),and cell spread area was increased(P<0.05)in the PRP group,CMC-OCS group,and CMC-OCS/PRP group;apoptosis rate was decreased in the CMC-OCS/PRP group(P<0.05),and collagen fiber I protein expression was increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05).(3)Compared with the control group,the number of cell migration was decreased(P<0.05),and the migration area had no significant change(P>0.05)in the H2O2 group.Compared with the H2O2 group,the number and area of cell migration were increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05),and the increase was most significant in the CMC-OCS/PRP group.(4)Under oxidative stress,CMC-OCS/PRP hydrogel can improve the migration ability of fibroblasts,resist cell apoptosis,and preserve cell extension function.

Objective To measure the Young's modulus values of the quadriceps muscles(rectus femoris,vastus intermedius,vastus lateralis,vastus medialis)and tendons in Parkinson's disease(PD)patients using real-time shear wave elastography(SWE)technology,and to analyze the changes in muscle and tendon tone.Methods A total of 60 clinically diagnosed PD patients from Yunnan University Affiliated Hospital between April 2023 and April 2024 were included in the study group.Based on the scores and ratings of PD rating scale,patients were divided into Group A(symptomatic side,n=60)and Group B(less symptomatic side,n=60).An additional 60 healthy subjects were selected as the control group.The shear wave elastography function of the ACUSON Sequoia ultrasound diagnostic device from Siemens USA was used to measure the Young's modulus values(kPa)of the quadriceps muscles and tendons in a relaxed state,and to analyze and compare the changes in muscle and tendon tone.Results The Young's modulus values of quadriceps muscles(rectus femoris,intermedius femoris,vastus lateralis,vastus medialis)in groups A and B were higher than those in control group(P<0.05).The Young's modulus values of the intermediate and lateral femoris muscles in group A were higher than that in group B(all P<0.05).The Young's modulus values of quadriceps tendon in groups A and B were higher than that in control group.(P<0.05).The Young modulus value of quadriceps tendon in group A was higher than that in group B(P<0.05).Conclusion Patients with Parkinson's disease exhibit increased muscle and tendon tone in the quadriceps.Notably,the muscle tone of the vastus intermedius and vastus lateralis on the symptomatic side is higher than that on the less symptomatic side,while there is no significant difference in muscle tone between the rectus femoris and vastus medialis on the symptomatic and less symptomatic sides.

Objective To explore the value of shear wave elastography(SWE)combined with carbohydrate antigen 15-3(CA15-3)in differentiating benign and malignant breast imaging and reporting data system(BI-RADS)category 4 breast masses.Methods Ninety patients with breast tumors confirmed by surgical pathology at the Affiliated Hospital of Yunnan University from December 2021 to June 2024 were enrolled,all with BI-RADS category 4 breast masses.The patients were divided into a benign group(n=42)and a malignant group(n=48)according to whether the breast masses were benign or malignant.All of them underwent SWE examination,and serum CA15-3 levels were determined using electrochemiluminescence method.Serum CA15-3 levels and SWE parameters[elasticity standard deviation(ESD),mean elasticity value(Emean),maximum elasticity value(Emax)and the ratio of breast mass elasticity to same-layer low fat elasticity(Eratio)]were compared between the two groups.The area under the receiver operating characteristic curve(AUC)was used to evaluate the diagnostic performance of serum CA15-3 levels,SWE parameters,and their combination for benign and malignant BI-RADS category 4 breast masses.Results The SWE parameters(ESD,Emean,Emax,and Eratio)and serum CA15-3 levels in the malignant group were significantly higher than those in the benign group(P<0.05).The AUC values of ESD,Emean,Emax,Eratio,and serum CA15-3 levels for the diagnosis of benign and malignant BI-RADS category 4 breast masses were 0.718(95%CI:0.613-0.824),0.791(95%CI:0.701-0.881),0.721(95%CI:0.615-0.826),0.721(95%CI:0.613-0.830)and 0.793(95%CI:0.702-0.885),respectively.Notably,SWE parameters combined with serum CA15-3 levels achieved an AUC value of 0.953(95%CI:0.917-0.992).Conclusion The combination of CA15-3 and SWE exhibits high efficiency in diagnosing the benign and malignant nature of BI-RADS category 4 breast masses.

Cardiovascular disease is one of the diseases with high global incidence and mortality rates,po-sing a serious threat to public health.Therefore,identifying early diagnostic and treatment targets is particu-larly important.Salusins are vasoactive peptides with various biological activities,and research has shown a close relationship between Salusins and cardiovascular disease.Salusins have two subtypes,Salusin-α and Sa-lusin-β.The main function of Salusin-α is to lower blood pressure,slow heart rate,reduce inflammation and oxidative stress,and inhibit atherosclerosis,while Salusin-β primarily promote proliferation of vascular smooth muscle cells and contribute to atherosclerosis.This article reviews some of the latest research progress on Sa-lusins.

BACKGROUND:At present,the dental composite resin filling material composed of resin matrix monomer is the first choice material for the filling treatment of dental defects,but with the increase of its use time in the oral environment,the dental tissue will develop secondary caries and the filling material will wear and break.The main cause of these problems is the polymerization shrinkage of the filling material and its mismatch with the mechanical properties of the dental tissue. OBJECTIVE:To synthesize a new type of dental composite resin monomer by adding initiators with different components,to improve the traditional double bond conversion rate of the system and further improve the mechanical properties of the material. METHODS:A new composite resin matrix system was prepared by adding different initiators to the monomer of 3,3′,5,5′-tetramethoxybiphenyl-4,4′-diol epoxy acrylate resin.In group A,camphorquinone with a mass fraction of 1.1%was added.In group B,1-phenyl-1,2-propanedione with a mass fraction of 2.1%was added.In group C,a mixture of camphorquinone and 1-phenyl-1,2-propanedione(a mass ratio of the two was 1:1)with a mass fraction of 3.1%was added.The double bond conversion,polymerization shrinkage and mechanical properties of the samples were determined. RESULTS AND CONCLUSION:(1)The double bond conversion rate of groups B and C was higher than that of group A(P<0.05).The polymerization shrinkage of group B was higher than that of group A(P<0.05),while that of group C was lower than that of group A(P<0.05).(2)The flexural strength,elastic modulus and compressive strength of groups B and C were higher than those of group A(P<0.05,P<0.01).Vickers hardness of group B was higher than that of group A(P<0.05),and the Vickers hardness of group C was lower than that of group A(P<0.01).(3)These findings suggest that 1-phenyl-1,2-propanedione is an initiator with ideal performance.The combined application of 1-phenyl-1,2-propanedione and camphorquinone can effectively improve the double bond conversion rate of the resin matrix system and further improve the mechanical property of the resin.

BACKGROUND:Previous studies have shown that human beta-defensin 3 has significant antifungal,antibacterial,and antiviral activities and plays an important bridging role in linking innate and acquired immune responses. OBJECTIVE:To observe the effect of human beta-defensin 3 hydrogel on treatment of periodontitis in rats. METHODS:Using Poloxamer 188 and 407 as the matrix,a blank hydrogel was constructed by cold solution.Human beta-defensin 3 hydrogel was prepared by mixing human beta-defensin 3 with the hydrogel.Twenty-five SD rats were randomly divided into five groups with five rats in each group:No treatment was given in the healthy group.The periodontitis model was constructed by the orthodontic ligature wire method in the periodontitis group,blank hydrogel group,minocycline hydrochloride group,and human beta-defensin 3 hydrogel group.8 weeks after modeling,blank hydrogel,minocycline hydrochloride,and human β-defensin 3 hydrogel were injected into the buccal and palatal periodontal bags,once a week,and relevant tests were carried out after continuous administration for 4 weeks. RESULTS AND CONCLUSION:(1)Compared with the healthy group,periodontal plaque index,gingival bleeding index,and periodontal probing depth were increased in the periodontitis group(P<0.01).Compared with the periodontitis group,the periodontal plaque index,gingival bleeding index,and periodontal probing depth of rats were decreased in the minocycline hydrochloride group and the human beta-defensin 3 hydrogel group(P<0.05).(2)Hematoxylin-eosin staining proved that the hydrogel was not toxic to the rat organism.(3)Stereomicroscopy and Micro CT showed that compared with the healthy group,the root exposure and the distance between enamel cementum boundary and alveolar crest of the periodontitis group were increased(P<0.05).Compared with the periodontitis group,the root exposure and the distance between enamel cementum boundary and alveolar crest of rats were reduced in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group(P<0.05).(4)Hematoxylin-eosin,Masson,and tartrate-resistant acid phosphatase staining showed that periodontal inflammation was obvious,fiber structure was disordered and osteoclasts were active in the periodontitis group and blank hydrogel group,while periodontal inflammation was decreased,fiber arrangement was more regular,and osteoclasts were reduced in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group.(5)qRT-PCR showed that compared with the healthy group,the mRNA expressions of interleukin 1β,tumor necrosis factor α,interleukin 6,and inducible nitric oxide synthase were increased in the periodontitis group(P<0.05).Compared with the periodontitis group,the mRNA expressions of interleukin 1β,tumor necrosis factor α,interleukin 6,and inducible nitric oxide synthase in gingival tissue of rats were decreased in the minocycline hydrochloride group and human beta-defensin 3 hydrogel group(P<0.05).(6)The results showed that human beta-defensin 3 hydrogel was able to attenuate inflammation in rat periodontal tissues by decreasing the relative expression of inflammatory factors and inhibiting osteoblasts.

BACKGROUND:Most of the formulas for the clinical treatment of premature ovarian insufficiency have evolved from the basic formula of Liuwei Dihuang Pills,and have achieved good therapeutic efficacy.Currently,most of the experimental studies on Liuwei Dihuang Pills focus on morphological observations and physiological and biochemical detection of in vivo animal models,while fewer studies on molecular mechanisms have been reported. OBJECTIVE:To explore the molecular mechanism of Liuwei Dihuang Pills in the treatment of premature ovarian insufficiency based on the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species pathway. METHODS:Premature ovarian insufficiency model was established in mice by intraperitoneal injection of cyclophosphamide 120 mg/kg combined with busulfan 12 mg/kg,and then Liuwei Dihuang Pill suspension was used to intervene in premature ovarian insufficiency mice.After 12 weeks of intervention,the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,anti-Mullerian hormone,8-hydroxydeoxyguanosine,total antioxidant capacity and reactive oxygen species in serum of mice were detected by ELISA method.The morphological changes in mouse ovaries were observed by hematoxylin-eosin staining.The ultrastructure of mouse follicular granulosa cells and the apoptosis of granulosa cell mitochondria were observed by transmission electron microscopy.The expression levels of receptor gamma coactivator-1 alpha and mitochondrial transcription factor A in mouse ovarian granulosa cells were detected by immunohistochemistry. RESULTS AND CONCLUSION:Compared with the model group,serum levels of follicle-stimulating hormone,luteinizing hormone,reactive oxygen species,and 8-hydroxydeoxyguanosine were decreased in the experimental group(P＜0.05),and the levels of estradiol,anti-Mullerian hormone,and total antioxidant capacity were increased(P＜0.05).Hematoxylin-eosin staining showed that in the model group,there were more atretic follicles and corpus luteum forms,some secondary follicles,and interstitial fibrosis and hyperplasia;in the experimental group,a large number of atretic follicles,few corpus luteum forms,primordial follicles were observed at the edges but there were few secondary follicles and no mature follicles.Transmission electron microscopy showed that the organelles in ovarian granulosa cells of mice in the experimental groups were relatively intact.Immunohistochemical results showed that compared with the model group,the expression level of receptor gamma coactivator-1 alpha in the ovarian tissue of mice increased slightly in the experimental group at the 4th week,and there was no significant change at the 8th and 12th weeks.The expression level of mitochondrial transcription factor A in the ovarian tissues of mice in the experimental group was transiently increased at the 4th week,and then slightly decreased,which were all significantly different from those of the model group.To conclude,Liuwei Dihuang Pills inhibit ovarian granulosa cell apoptosis in mice with premature ovarian insufficiency to a certain extent through the receptor gamma coactivator-1 alpha/mitochondrial transcription factor A/reactive oxygen species signaling pathway,thereby improving the endocrine function of the ovary,enhancing the antioxidant capacity,and attenuating the degree of oxidative stress damage.

Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess anti-insomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmaco-metabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine N-methyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.