The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

Objective:To investigate the preventive efficacy of triamcinolone acetonide injection on esophageal stenosis after endoscopic submucosal dissection (ESD).Methods:From February 1, 2021 to October 31, 2023, 82 patients who underwent ESD for esophageal lesions at the Affiliated Cancer Hospital of Nanjing Medical University (Jiangsu Cancer Hospital) were enrolled. According to the treatment of the surface after ESD, the patients were divided into the triamcinolone acetonide group (49 cases) and the no-special-treatment group (33 cases). The patients of triamcinolone acetonide group received multiple injections of triamcinolone acetonide solution post-ESD (immediate), week 1, and week 4, while the patients of no-special-treatment group did not receive additional pharmacological intervention. The patients were followed up for 3 months after ESD. The occurrence of esophageal stenosis after ESD was observed under endoscopy. The incidence of esophageal stenosis and the improvement of dysphagia after ESD were compared between the triamcinolone acetonide group and no-special-treatment group. Univariate and multivariate logistic regression analyes were performed to identify influencing factors of esophageal stenosis after ESD. Chi-square test was used for statistical analysis.Results:The incidence of esophageal stenosis after ESD in the triamcinolone acetonide group was lower than that in the no-special-treatment group (16.3% (8/49) vs. 66.7% (22/33)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (83.7% (41/49) vs. 33.3% (11/33)), and the differences were statistically significant ( χ2=19.42 and 24.31, both P<0.001). In 42 patients with circumferential esophageal lesions involving >75%, the incidence of esophageal stenosis in the triamcinolone acetonide group was lower than that in the no-special-treatment group (28.6% (6/21) vs. 85.7% (18/21)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (71.4% (15/21) vs. 14.3% (3/21)), and the differences were statistically significant ( χ2=11.76 and 15.33, both P<0.001). There was no statistically significant differences in the incidence of adverse events between the triamcinolone acetonide group and no-special-treatment group (4.1% (2/49) vs. 0; χ2=0.20, P=0.656), and no serious adverse reactions occurred in 2 groups. The results of multivariate logistic regression analysis showed that the long distance from the proximal lesion margin to the incisors was a protective factor of whether esophageal stenosis occured or not after ESD ( OR=0.795, 95% confidence interval (95% CI): 0.652 to 0.947, P=0.014), while the incidence of esophageal stenosis increased in patients with circumferential lesions involving >75% ( OR=7.064, 95% CI: 1.893 to 32.408, P=0.006), and the incidence of esophageal stenosis effectively reduced after the use of triamcinolone acetonide post ESD ( OR=0.062, 95% CI: 0.013 to 0.229, P<0.001). Conclusion:After ESD, triamcinolone acetonide can reduce the incidence of esophageal stenosis and improve patients′ dysphagia.

OBJECTIVE To investigate the effects of combined exposure of silica nanoparticles(SiNPs)and a high-fat diet(HFD)on aortic vascular fibrosis in rats and explore the underlying mecha-nisms.METHODS Transmission electron microscopy and a particle size analyzer were used to analyze the size and dispersion of SiNPs.Male Wistar rats were randomly divided into four groups:standard diet control group(STD-control),standard diet SiNPs group(STD+SiNPs),high-fat diet control group(HFD-control),and high-fat diet SiNPs group(HFD+SiNPs).The rats received intratracheal instillation of SiNPs(10 mg·kg-1)or saline combined with either an STD or HFD every four days for 90 days.Small animal ultrasound was used to evaluate vascular function and structure.Hematoxylin and eosin(HE)staining and Masson's staining were performed to analyze aortic pathology and fibrosis.Biochemical assays were conducted to measure superoxide dismutase(SOD)activity,malondialdehyde(MDA)contents,and the ratio of reduced gluta-thione/glutathione disulfide(GSH/GSSG).Immunohistochemistry and Western blotting were used to analyze the expression levels of mitophagy-related proteins phospha-tase and PTEN induced kinase 1(PINK1),E3 ubiquitinligase(Parkin),microtubule-associated protein 1 light chain 3B(LC3B),and P62,as well as vascular fibrosis marker proteins alpha-smooth muscle actin(α-SMA),typeⅠcollagen(Col-Ⅰ),and typeⅢcollagen(Col-Ⅲ).RESULTS Transmission electron micros-copy analysis showed that SiNPs had a uniform size(51.24±8.54)nm,regular morphology,and good dispersion.Compared with the STD-control group,the STD+SiNPs group exhibited a significant reduc-tion in the end-diastolic diameter of the left common carotid artery and aorta,along with a significant increase in intima-media thickness.Additionally,SOD activity decreased,MDA contents increased,and the GSH/GSSG ratio declined,indicating that SiNPs exposure induced oxidative damage and vascular dysfunction in the aorta.Pathological staining revealed that SiNPs caused inflammatory infiltration and vascular fibrosis in the aortic intima of rats.Notably,HFD exacerbated the vascular toxicity induced by SiNPs,suggesting a synergistic effect of their combined exposure.Mechanistically,immunohistochem-istry and Western blotting results showed that the combined exposure to SiNPs and HFD significantly upregulated the expressions of PINK1,Parkin,LC3BⅡ/Ⅰ,P62,α-SMA,Col-Ⅰ,and Col-Ⅲin the aorta.These findings suggested that SiNPs and HFD co-exposure might activate PINK1/Parkin-mediated mitophagy,contributing to the progression of aortic fibrosis.CONCLUSION Combined exposure to SiNPs and HFD might induce mitophagy through the PINK1/Parkin signaling pathway,leading to decreased vascular antioxidant capacity and fibrosis.These findings provided new evidence for the joint impact of SiNPs exposure and metabolic disorders on cardiovascular health.

Objective:To investigate the preventive efficacy of triamcinolone acetonide injection on esophageal stenosis after endoscopic submucosal dissection (ESD).Methods:From February 1, 2021 to October 31, 2023, 82 patients who underwent ESD for esophageal lesions at the Affiliated Cancer Hospital of Nanjing Medical University (Jiangsu Cancer Hospital) were enrolled. According to the treatment of the surface after ESD, the patients were divided into the triamcinolone acetonide group (49 cases) and the no-special-treatment group (33 cases). The patients of triamcinolone acetonide group received multiple injections of triamcinolone acetonide solution post-ESD (immediate), week 1, and week 4, while the patients of no-special-treatment group did not receive additional pharmacological intervention. The patients were followed up for 3 months after ESD. The occurrence of esophageal stenosis after ESD was observed under endoscopy. The incidence of esophageal stenosis and the improvement of dysphagia after ESD were compared between the triamcinolone acetonide group and no-special-treatment group. Univariate and multivariate logistic regression analyes were performed to identify influencing factors of esophageal stenosis after ESD. Chi-square test was used for statistical analysis.Results:The incidence of esophageal stenosis after ESD in the triamcinolone acetonide group was lower than that in the no-special-treatment group (16.3% (8/49) vs. 66.7% (22/33)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (83.7% (41/49) vs. 33.3% (11/33)), and the differences were statistically significant ( χ2=19.42 and 24.31, both P<0.001). In 42 patients with circumferential esophageal lesions involving >75%, the incidence of esophageal stenosis in the triamcinolone acetonide group was lower than that in the no-special-treatment group (28.6% (6/21) vs. 85.7% (18/21)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (71.4% (15/21) vs. 14.3% (3/21)), and the differences were statistically significant ( χ2=11.76 and 15.33, both P<0.001). There was no statistically significant differences in the incidence of adverse events between the triamcinolone acetonide group and no-special-treatment group (4.1% (2/49) vs. 0; χ2=0.20, P=0.656), and no serious adverse reactions occurred in 2 groups. The results of multivariate logistic regression analysis showed that the long distance from the proximal lesion margin to the incisors was a protective factor of whether esophageal stenosis occured or not after ESD ( OR=0.795, 95% confidence interval (95% CI): 0.652 to 0.947, P=0.014), while the incidence of esophageal stenosis increased in patients with circumferential lesions involving >75% ( OR=7.064, 95% CI: 1.893 to 32.408, P=0.006), and the incidence of esophageal stenosis effectively reduced after the use of triamcinolone acetonide post ESD ( OR=0.062, 95% CI: 0.013 to 0.229, P<0.001). Conclusion:After ESD, triamcinolone acetonide can reduce the incidence of esophageal stenosis and improve patients′ dysphagia.

OBJECTIVE To investigate the effects of combined exposure of silica nanoparticles(SiNPs)and a high-fat diet(HFD)on aortic vascular fibrosis in rats and explore the underlying mecha-nisms.METHODS Transmission electron microscopy and a particle size analyzer were used to analyze the size and dispersion of SiNPs.Male Wistar rats were randomly divided into four groups:standard diet control group(STD-control),standard diet SiNPs group(STD+SiNPs),high-fat diet control group(HFD-control),and high-fat diet SiNPs group(HFD+SiNPs).The rats received intratracheal instillation of SiNPs(10 mg·kg-1)or saline combined with either an STD or HFD every four days for 90 days.Small animal ultrasound was used to evaluate vascular function and structure.Hematoxylin and eosin(HE)staining and Masson's staining were performed to analyze aortic pathology and fibrosis.Biochemical assays were conducted to measure superoxide dismutase(SOD)activity,malondialdehyde(MDA)contents,and the ratio of reduced gluta-thione/glutathione disulfide(GSH/GSSG).Immunohistochemistry and Western blotting were used to analyze the expression levels of mitophagy-related proteins phospha-tase and PTEN induced kinase 1(PINK1),E3 ubiquitinligase(Parkin),microtubule-associated protein 1 light chain 3B(LC3B),and P62,as well as vascular fibrosis marker proteins alpha-smooth muscle actin(α-SMA),typeⅠcollagen(Col-Ⅰ),and typeⅢcollagen(Col-Ⅲ).RESULTS Transmission electron micros-copy analysis showed that SiNPs had a uniform size(51.24±8.54)nm,regular morphology,and good dispersion.Compared with the STD-control group,the STD+SiNPs group exhibited a significant reduc-tion in the end-diastolic diameter of the left common carotid artery and aorta,along with a significant increase in intima-media thickness.Additionally,SOD activity decreased,MDA contents increased,and the GSH/GSSG ratio declined,indicating that SiNPs exposure induced oxidative damage and vascular dysfunction in the aorta.Pathological staining revealed that SiNPs caused inflammatory infiltration and vascular fibrosis in the aortic intima of rats.Notably,HFD exacerbated the vascular toxicity induced by SiNPs,suggesting a synergistic effect of their combined exposure.Mechanistically,immunohistochem-istry and Western blotting results showed that the combined exposure to SiNPs and HFD significantly upregulated the expressions of PINK1,Parkin,LC3BⅡ/Ⅰ,P62,α-SMA,Col-Ⅰ,and Col-Ⅲin the aorta.These findings suggested that SiNPs and HFD co-exposure might activate PINK1/Parkin-mediated mitophagy,contributing to the progression of aortic fibrosis.CONCLUSION Combined exposure to SiNPs and HFD might induce mitophagy through the PINK1/Parkin signaling pathway,leading to decreased vascular antioxidant capacity and fibrosis.These findings provided new evidence for the joint impact of SiNPs exposure and metabolic disorders on cardiovascular health.

Objective To investigate the effect of comprehensive nursing measures on preventing venous thromboembolism(VTE)in elderly patients.Methods A total of 182 inpatients from the First Affiliated Hospital of Guangxi Medical University from January 2021 to December 2022 were selected and divided into observation group(92 cases)and control group(90 cases)according to random number table method.Patients in control group were given VTE prevention by conventional methods,and patients in observation group were given VTE comprehensive preventive measures.After the implementation of preventive measures,VTE prevention compliance and health self-management"knowledge-attitude-practice"were compared between two groups.Results There was no significant difference in the assessment of VTE risk level between two groups(P>0.05).The compliance of observation group was significantly better than that of control group(P<0.05).There were statistically significant differences between two groups in understanding and mastering VTE prevention knowledge,believing that VTE prevention measures were difficult to adhere to,and implementing VTE prevention according to medical advice(P<0.05).Patients in observation group had better health self-management.Conclusion The comprehensive nursing intervention of patients participating in VTE risk assessment and jointly implementing thrombosis prevention measures between nurses and patients can improve the compliance of VTE prevention and health self-management ability of elderly patients,which is of great significance for reducing the occurrence of VTE.

bstract: Objective To elucidate the distribution characteristics of mosquito species and the population genetic diversity of important mosquito species in the Wuyi Mountain Nature Reserve, with the aim of providing a scientific basis for the prevention and control of mosquito-borne diseases in the region. Methods Within Wuyi Mountain Nature Reserve 2022- 2023, 16 sampling sites were selected, where larvae were collected using the pipette method and adult mosquitoes were collected using the mosquito trap lamp method. Mosquito species identification was accomplished by integrating morphological characteristics and molecular identification techniques based on CO Ⅰ and CO Ⅱ gene sequences. Software tools such as ClustalX, DnaSP v5.0, and Network v4.6.1.0 were utilized to analyze the genetic differentiation (Fst), gene flow (Nm) among populations of Aedes japonicus, Aedes albopictus and Armigeres subalbatus. Results The mosquito specimens collected from the Wuyi Mountain Nature Reserve were identified as 30 species belonging to 8 genera within the Culicidae family. Among them, there were 10 species of Aedes, 13 species of Culex, 1 species each of Armigeres, Orthopodomyia, Uranotaenia, Tripyeroides, and Anopheles, and 2 species of Toxorhynchites. Analysis of the genetic structure of important mosquito populations showed that the haplotype diversity index (Hd) of Ae. japonicus was 0.994 7, with a generally moderate degree of differentiation between populations and a higher degree of genetic differentiation between populations 6 and 12; Aedeslbopictus had a haplotype diversity index of 0.634 0, with significant genetic differentiation between populations 1 and 2 compared to other groups; Armigeres subalbatus had a haplotype diversity index of 0.703 3, with substantial genetic differentiation and limited gene flow between population 2 and populations 3, 4, 6, and 7. Conclusions The mosquito species are rich in Wuyi Mountain Nature Reserve. A comprehensive survey of the composition and distribution of mosquito populations was carried out, and the characteristics of the population genetic structure of the important species of Ae. japonicus, Ae. Albopictus, and Ar. subalbatus populations were analyzed, providing valuable scientific data reference for local mosquito-borne ecological research and disease prevention and control.

BACKGROUND:Astrocytes play an important role in the pathology of central nervous system diseases.The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases.Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response.Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE:To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS:Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro.CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT.The astrocytes were divided into five groups:PBS group,lipopolysaccharide group,lipopolysaccharide + astragaloside group,lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group.The secretion level of inflammatory factors was detected by ELISA,and the level of nitric oxide was detected by Griess method.The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells.The expression of astrocyte activation marker GFAP,A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining.The expressions of CFB,C3,S100A10,PTX3,Notch-1,Jag-1,and Hes were detected by western blot assay. RESULTS AND CONCLUSION:(1)According to the results of CCK8 assay,the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments.(2)Compared with PBS group,interleukin-6,interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased(P<0.05,P<0.05,P<0.01).Compared with the lipopolysaccharide group,interleukin-6(all P<0.05),interleukin-12(P>0.05,P<0.05,P<0.05)and nitric oxide(P<0.05,P<0.01,P<0.01)secretion significantly reduced in the lipopolysaccharide + astragaloside group,lipopolysaccharide +DAPT group,lipopolysaccharide + DAPT + astragaloside group.(3)Compared with the PBS group,the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group(P<0.01).Compared with the lipopolysaccharide group,astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group(P<0.05,P<0.05,P<0.01).(4)Compared with the PBS group,the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased(P<0.01,P<0.05),and the expressions of A2 markers S100A10 and PTX3 were decreased(P<0.01,P<0.05).Compared with the lipopolysaccharide group,C3(all P<0.01)and CFB(both P<0.05)were significantly reduced and S100A10(all P<0.01)and PTX3(P<0.05,P<0.05 and P>0.05)were increased in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(5)Compared with the PBS group,the expressions of Jag-1,Notch-1 and Hes in the lipopolysaccharide group were significantly increased(all P<0.01).Compared with the lipopolysaccharide group,the expressions of Jag-1(all P<0.01),Notch-1(all P<0.01)and Hes(P<0.05,P<0.01 and P<0.01)were significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(6)The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway,reduce the secretion of inflammatory factors and the migration of CD4 T cells,and thus inhibit astrocyte activation and inflammatory response.

BACKGROUND: Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups. METHODS: A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software ( http://www.R-project.org/ ) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio. RESULTS: The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) ( P  = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely ( P  = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) ( P  = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) ( P  = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes. CONCLUSIONS In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines show significant effects.
Pregnancy ; Humans ; Female ; Male ; Retrospective Studies ; COVID-19/prevention & control* ; Embryo Transfer ; Fertilization in Vitro ; Pregnancy Rate ; Vaccination