ObjectiveTo explore the possible mechanisms of electroacupuncture at Fengchi （GB 20）， Waiguan （TE 5）， and Yanglingquan （GB 34） in treating chronic migraine from the perspective of nociceptive sensitization. MethodsForty SPF-grade SD rats were randomly divided into blank group， model group， electroacupuncture group， electroacupuncture + agonist group， and inhibitor group， with 8 rats in each group. Except for the blank group， rats were injected intraperitoneally with nitroglycerin to establish a chronic migraine rat model. After successful modeling， the electroacupuncture group received electroacupuncture at bilateral "Fengchi" （GB 20）， "Waiguan" （TE 5）， and "Yanglingquan" （GB 34） for 30 minutes each session. The electroacupuncture + agonist group received the same electroacupuncture treatment and additional injection of protein kinase C （PKC） agonist Phorbol 12-myristate 13-acetate （1.0 ng/μl， 25 μl） via the infraorbital foramen. The inhibitor group received PKC inhibitor Chelerythrine Chloride （1.0 ng/μl， 10 μl） via the infraorbital foramen. The blank group， model group， and inhibitor group underwent restraint for 30 minutes without other interventions. All groups were continuously intervened for 5 days. After the intervention， the nociceptive thresholds （mechanical and thermal pain） of the periorbital area and hind paw were measured. The expression levels of transient receptor potential vanillic acid subtype 1 （TRPV1）， phosphorylated TRPV1 （p-TRPV1）， PKC proteins， Trpv1， Pkc mRNA， and the average fluorescence intensity of transient receptor potential vanillic acid subtype 1 （TRPV1） and PKC in the trigeminal ganglion were detected using Western Blot， real-time fluorescence quantitative PCR， and immunofluorescence methods. ResultsCompared with the blank group， the mechanical and thermal pain thresholds of the periorbital area and hind paw were reduced in the model group， and the protein levels of TRPV1， PKC， p-TRPV1， as well as the mRNA expression of Trpv1 and Pkc， and the average fluorescence intensity of TRPV1 and PKC in the trigeminal ganglion significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， the electroacupuncture group exhibited increased mechanical and thermal pain thresholds in the periorbital and hind paw areas， and decreased protein levels of TRPV1， PKC， p-TRPV1， mRNA expression of Trpv1 and Pkc， and average fluorescence intensity of TRPV1. In the electroacupuncture + agonist group， the average fluorescence intensity of TRPV1 in the trigeminal ganglion decreased. The inhibitor group exhibited increased mechanical pain thresholds in the periorbital area and thermal pain thresholds in the hind paw， along with decreased protein levels of TRPV1， PKC， p-TRPV1， and the average fluorescence intensity of TRPV1 and PKC （P＜0.05 or P＜0.01）. Compared with the electroacupuncture group， the electroacupuncture + agonist group showed an increase in the protein levels of TRPV1， PKC， p-TRPV1， and the mRNA expression of Trpv1 （P＜0.05 or P＜0.01）. ConclusionElectroacupuncture at the "Fengchi" （GB 20）， "Waiguan" （TE 5）， and "Yanglingquan" （GB 34） acupoints can increase the mechanical and thermal pain thresholds in chronic migraine rats and alleviate nociceptive sensitization. The mechanism may be related to the inhibition of PKC/TRPV1 pathway.

The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

The organoid co-culture model, as a novel tool for recreating a three-dimensional microenvironment to study cell-cell interactions, has demonstrated significant application potential in biomedical research in recent years. By simulating the in vivo tissue microenvironment, this model provides a more precise experimental platform for investigating complex cellular interactions, particularly in areas such as tumor immune evasion mechanisms, drug sensitivity testing, and the pathological characterization of neurodegenerative diseases, where it has demonstrated significant value. However, the organoid co-culture model still faces several challenges in terms of standardized procedures, large-scale cultivation, ethical guidelines, and future development. In particular, in the field of laboratory animal science, how to effectively combine organoids with traditional animal models, and how to select the most appropriate model for different research needs while exploring its potential for replacement, remain pressing issues. In the context of ethical approval and the replacement of animal experiments, the organoid co-culture model offers an experimental approach that better aligns with the "3R" principle (Replacement, Reduction, Refinement), potentially becoming an important tool for replacing traditional animal models. To this end, this paper reviews the latest advances and key challenges in this field, providing a detailed description of the construction methods for organoid co-culture models and discussing their applications in disease mechanism research and drug screening. The paper also systematically compares the organoid co-culture models with traditional animal models, exploring the criteria for selecting the appropriate model for specific applications. Furthermore, this paper discusses the potential value of organoid co-culture models as alternatives to animal experiments and anticipates future development trends of this technology. Through these discussions, the paper aims to promote the innovation and development of organoid co-culture technology and provide new perspectives and scientific evidence for future research.

BACKGROUND:Calcium phosphate(CaP)coatings are widely used to improve the integration of titanium implants into bone but these coatings are associated with risks of infection.It is thus desirable to confer antibacterial properties to CaP coatings. OBJECTIVE:To prepare CaP-MgO composite coatings by impregnating magnesium oxide(MgO)sol into CaP coatings and assess the in vitro antibacterial activities and cytocompatibility. METHODS:An electrolyte was determined by titration and used for CaP coating electrodeposition on titanium(referred to as Ti-CaP).MgO was impregnated into the coating by immersing in an MgO sol with different mass fractions(15%,30%,50%)and subsequently calcined to form MgO-CaP composite coatings,which were recorded as Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg,respectively.Microstructure,tensile properties,critical load,and Mg2+ release of coatings in vitro were characterized.Antibacterial activity was assayed using spread plate method by culturing S.aureus on the pure titanium sheet surface and Ti-CaP,Ti-Cap-15mg,Ti-Cap-30mg and Ti-Cap-50mg surfaces for 24 and 48 hours.Mouse osteoblast suspension was inoculated on pure titanium sheets and Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg coated titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay,and cell survival rate was calculated.The morphology of composite coating soaked in DMEM was also observed. RESULTS AND CONCLUSION:(1)Homogeneous,microporous CaP coatings consisting of octacaclium phosphate crystal flakes were prepared on titanium by electrodeposition.After sol impregnation-calcination,MgO aggregates were filled into the inter-flake voids.The extent of MgO filling and Mg concentration in the coating increased with the number of sol impregnation procedures.When immersed in phosphate buffered saline,all composite coatings actively released Mg2+ within 1 day;subsequently,the Mg2+ release slowed down on day 3.A small amount of Mg2+ release was still detected on day 7.The yield strength,tensile strength and fracture growth rate of Ti-CaP-30Mg coated titanium were not significantly different from those of pure titanium(P>0.05).There was no significant difference in the critical load of Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups(P>0.05).(2)Except that pure titanium sheet and Ti-CaP had no antibacterial properties,the other samples had good antibacterial properties,and the antibacterial rate increased with the increase of MgO content in the coating.(3)After 1 and 3 days of co-culture,the cell survival rate of Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups was lower than that of pure titanium group and Ti-CaP group(P<0.05).After 5 and 7 days of culture,there was no significant difference in cell survival rate among five groups(P>0.05).The content of MgO in the coating decreased gradually with the time of immersion in the medium.(4)The MgO sol impregnation added antibacterial properties to the CaP coatings while retained their biocompatibility.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Background: Dermoscopy enhances detection of basal cell carcinoma (BCC), especially for the pigmented subtype common among Asians. However, there is limited data on dermoscopic features of BCC in Filipinos. Objectives: The objective of this study is to describe the clinicopathologic profile and dermoscopic features of BCC in Filipinos seen in a tertiary care clinic. Methods: A cross-sectional study was conducted in the Philippines from November 2019 to December 2021 in a tertiary care clinic. Fifty-three (53) lesions suspicious for BCC were analyzed using dermoscopy prior to histologic confirmation. Fifty (50) biopsy-proven BCC lesions were included in the analysis. Results: Lesions were more commonly seen in females (72.50%), and located on the head and neck (88%). The most common histopathologic subtype was nodular (74%). The most common dermoscopic features were large blue-gray ovoid nests (86%) and ulcerations (70%). Conclusion The most common BCC type among the study participants was nodular, with large blue-gray ovoid nests and ulceration seen on dermoscopy.
carcinoma, basal cell ; dermoscopy

ObjectiveTo investigate the possible mechanism of electroacupuncture at Fengchi （GB 20）， Yanglingquan （GB 34） and Waiguan （TE 5） for acute migraine attacks by peroxisome proliferator-activated receptor γ/ nuclear transcription factor-κB pathway in the trigeminal neurovascular system. MethodsForty SD rats were randomly divided into blank group， model group， electroacupuncture group， electroacupuncture plus inhibitor group， and agonist group， 8 rats in each group. Except for the blank group， rats were injected with inflammation decoction intracranial catheter to establish rat models of acute migraine. Thirty minutes after modelling， the electroacupuncture group was given 0.9% NaCl solution by intraperitoneal injection and then electroacupuncture at "Fengchi" （GB 20）， "Yanglingquan" （GB 34）， and "Waiguan" （TE 5） for 30 mins； the electroacupuncture plus inhibitor group was given PPARγ inhibitor T0070907 （1.5 mg/kg） and eclectroacupuncture as the above for 30 mins； the agonist group was given PPARγ inhibitor pioglitazone hydrochloride （10 mg/kg） for 30 mins. Rats in the blank group and the model group were injected intraperitoneally with 0.9% NaCl solution and then bound and restrained for 30 mins. Behavioural scores were evaluated before modelling， 30 mins after modelling （pre-intervention） and post-intervention； after the last behavioural test， PPARγ， NF-κB p65 mRNA content in rat dura mater was detected by real-time fluorescence quantitative PCR； protein expression of PPARγ， NF-κB p65， interleukin 6 （IL-6）， tumour necrosis factor α （TNF-α） in spinal trigeminal nucleus of rats was detected by protein blotting； immunofluorescence double-labelling method was used to detect the fluorescence intensity of PPARγ， NF-κB p65 in spinal trigeminal nucleus of rats. ResultsCompared with the blank group at the same time， the behavioural scores of rats in the remaining groups increased after modelling and after intervention （P＜0.01）. Compared with the model group at the same time， the beha-vioural scores of rats in the electroacupuncture group， electroacupuncture plus inhibitor group， and agonist group decreased after the intervention （P＜0.01）. Compared with the electroacupuncture group at the same time， beha-vioural scores reduced in the agonist group and elevated in the electroacupuncture plus inhibitor group after intervention （P＜0.01）. Compared with the blank group， expression of PPARγ and NF-κB p65 mRNA elevated in the dura mater of rats in the model group， and expression of PPARγ， NF-κB p65， IL-6， and TNF-α protein enhanced in spinal trigeminal nucleus， and the fluorescence intensity of PPARγ and NF-κB p65 enhanced （P＜0.01）. Compared with the model group， PPARγ mRNA expression in dura mater elevated and NF-κB p65 mRNA expression reduced in each intervention group， PPARγ protein expression in spinal trigeminal nucleus enhanced， and NF-κB p65， IL-6， and TNF-α protein expression weakened； in the electroacupuncture group and the agonist group， PPARγ fluorescence intensity enhanced， and the fluorescence intensity of NF-κB p65 weakened in each intervention group （P＜0.05 or P＜0.01）. Compared with the electroacupuncture group， in the electroacupuncture plus inhibitor group， PPARγ mRNA， protein expression and fluorescence intensity reduced， NF-κB p65 mRNA， protein expression and fluorescence intensity elevated， and IL-6 and TNF-α protein expression enhanced； in the agonist group， PPARγ mRNA and protein expression elevated， NF-κB p65 mRNA and protein expression reduced， and IL-6 and TNF-α protein expression decreased （P＜0.05 or P＜0.01）. ConclusionElectroacupuncture at "Fengchi" （GB 20）， "Yanglingquan" （GB 34） and "Waiguan" （TE 5） can can reduce the symptoms of acute migraine attacks in rats， and its mechanism may be related to the up-regulation of PPARγ expression and the reduction of NF-κB expression， thus inhibiting the neurogenic inflammatory response.

Pyroptosis, a form of inflammatory cell death mediated by the Gasdermins family, promotes the release of inflammatory mediators and activates immune cell populations such as NK cells, T cells and macrophages in the tumor microenvironment(TME) to exert immune-regulating and anti-tumor effects. Glioblastoma(GBM) is the most serious and malignant glioma, and the median survival of patients diagnosed with GBM is less than 2 years, and the presence of the blood-brain barrier makes it difficult to deliver drugs to the brain, thus affecting the effect of drugs against GBM. Therefore, it is important to explore new measures and mechanisms to treat GBM, which has a complex TME with a large number of immune cell populations that are often immunosuppressed by GBM. Cellular pyroptosis as a mode of cell death capable of activating immunity, has the effect of activating the body’s immunity to help reverse TME immunosuppression. This review will focus on the relationship between cell pyroptosis and the immune system, how cell pyroptosis affects the immune cell population of TME in GBM, and the new progress in drug research on cell pyroptosis pathways in GBM treatment, providing new directions and strategies for future clinical treatment of GBM.

Objective To investigate the antitumor effects of ethoxydihydrosanguinarine(ESG)on colorectal cancer cells and its possible mechanisms.Methods Colorectal cancer cell lines RKO and HRT-18 were used.The cells were divided into blank control group and drug treatment groups(1.0,1.5,2.0 μmol/L ESG).CCK-8 assay,real time cellular analysis(RTCA)and colo-ny formation assay were used to detect the effect of ESG on cell proliferation and survival.Flow cytometry,DAPI staining,JC-1 mitochondrial membrane potential assay,and reactive oxygen species detection were performed to detect the effect of ESG on cell apoptosis.High-content analysis and Transwell invasion assay were used to detect the effect of ESG on cell invasion and mi-gration.Western blot was used to detect the expression of apoptosis,invasion and migration-related proteins,and the expression and phosphorylation of epidermal growth factor receptor(EGFR)and Akt/ERK signaling pathway proteins.The roles of EGFR in ESG-induced apoptosis,proliferation,invasion,and migration inhibition in colorectal cancer cells were detect through overex-pression and knockdown of EGFR.The direct binding between ESG and EGFR was detected by molecular docking and drug af-finity responsive target stability assay.Results The result showed that the proliferation and colony formation ability of colorec-tal cancer cells were significantly inhibited by ESG.Apoptosis through mitochondrial pathway was induced by ESG.The inva-sion and migration ability of colorectal cancer cells were inhibited by ESG.Moreover,ESG directly bound to EGFR and down-regulated the phosphorylation levels of Akt and ERK.Conclusion ESG targets and inhibits EGFR,thereby inhibiting the malig-nant progression of colorectal cancer cells and inducing mitochondrial apoptosis through its downstream Akt/ERK signaling pathway.This study provides new targeted drugs for targeting EGFR in the treatment of colorectal cancer.

Objective To summarize the experience of infectous endocarditis(IE)emergency surgery.Methods A total of 76 patients admitted to the department of cardiovascular surgery of the First Affiliated Hospital of Soochow University from January 2019 to August 2022 were retrospectively analyzed.Summarize and share treatment experience.Results Out of 76 IE patients,55 cases(72.4%)were male and 21 patients(27.6%)were female.The ratio of male to female was 2.6∶1.The age ranged from 17-76 years,with a mean of(52.1±15.6)years.The positive rate of blood culture was 25.0%(19 cases).A total of 57 cases(75.0%)were cured,8 cases(10.5%)were discharged automatically,9 cases(11.8%)were improved,and 2 patients(2.6%)died before operation.There were 30 patients(39.5%)who underwent mitral valve surgery,24 patients(31.6%)who underwent aortic valve surgery,12 patients(15.7%)who underwent mitral and aortic valve surgery;15 patients(19.7%)with congenital heart disease,69 patients(90.8%)with rheumatic heart disease;66 patients(93.0%)with left cardiac system vegetations,4 patients(5.6%)with right cardiac systems vegetations;13 patients(17.1%)who requied emergency surgery,and no death.Conclusions The mortality of IE is high,and the current effective treatment is still surgery,but the timing of surgery is still controversial.This study summarized the experience of several cases of emergency operation and concluded that as long as the patient's condition permits,early operation can improve the survival rate of patients and improve the prognosis.