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.

Atherosclerosis （AS） is a chronic inflammatory pathological process in which lipid and/or fibrous substances are deposited in the intima of arteries， and it is one of the pathological bases of many cardiovascular and cerebrovascular diseases. Endoplasmic reticulum stress （ERS） is a protective mechanism of cell adaptation. Moderate ERS can reduce abnormal protein aggregation and increase the degradation of misfolded proteins to repair and stabilize the internal environment， while excessive ERS can cause unfolded protein reaction， activate inflammation， oxidative stress， apoptosis， autophagy， and other downstream pathways， and lead to cell damage， or even apoptosis. A large number of studies have shown that ERS mediates a variety of pathological processes related to AS， affects endothelial cells， smooth muscle cells， macrophages， endothelial progenitor cells， and other cell components closely related to its occurrence and development， influences the progress of AS by regulating cell function， and promotes the formation of AS plaque， the transformation of stable plaque to unstable plaque， and the rupture of unstable plaque. Regulation of ERS may be a key target for the prevention and treatment of AS， and it is a research hotspot at present. Traditional Chinese medicine （TCM） believes that the origin of AS is the imbalance of Yin and Yang， the disharmony of Zangfu organs， and the abnormal operation of Qi， blood， and body fluid， which leads to the accumulation of phlegm， blood stasis， and other pathological products in the pulse channels， making the blood flow blocked or misfunction and causing the disease， which belongs to the syndrome of deficiency in origin and excess in superficiality. As the pathogenesis of AS is complex， and the symptoms are diverse， TCM has significant advantages in treating AS because of its multiple targets， multiple pathways， stable efficacy， strong individualization， and high safety. This paper systematically elaborated on the role of ERS in the occurrence and development of AS and summarized the mechanism research on the regulation and control of ERS by Chinese herbal monomer， Chinese herbal extract， Chinese herbal compound， and proprietary medicine， so as to provide a theoretical basis for clinical research and drug development in the prevention and treatment of AS.

Objective To investigate the association between electrode fusion error and improve-ment of depression during subthalamic nucleus-deep brain stimulation(STN-DBS)surgery for Parkinson's disease(PD).Methods A prospective trial was conducted on 240 PD patients under-going STN-DBS treatment in our hospital from January 2020 to December 2022.According to their clinical outcomes,they were divided into effective group(211 cases)and ineffective group(29 cases).The electrode fusion error was compared among the patients with different efficacy,psychological status,and cognitive status to analyze the correlation of electrode fusion error dur-ing STN-DBS surgery with improvement of depression and cognition.Results There were no sig-nificant differences between the effective group and ineffective group in terms of gender,age,body mass index,hypertension,diabetes,hyperlipidemia,disease duration,or preoperative MMSE and PDQ-39 scores(P＞0.05).STN-DBS treatment resulted in obviously improved clinical symptoms such as tremor,rigidity and bradykinesia,and higher UPDRSⅢ score when compared with the re-sults of preoperative impact test(P＜0.01).Before treatment,no statistical differences were ob-served in the scores of SAS,SDS,MoCA,MMSE,Alzheimer's disease assessment scale cognitive subscale(ADAS-Cog)or Chinese medicine syndrome change overall impression scale(CGIC-S)between the effective and ineffective groups(P＞0.05).After treatment,the scores of SAS,SDS,CGIC-S and ADAS-Cog were declined(P＜0.01),and these four scores was notably lower in the effective than the ineffective groups(P＜0.01).The scores of MoCA and MMSE were significant-ly elevated in both groups after surgery(P＜0.01),and the scores were higher in the effective group than the ineffective group(P＜0.01).The target coordinate deviation on the left and right was significantly higher in the patients with SDS≥53 and SAS≥50 than those of SDS＜53 and SAS＜50(P＜0.01).The target coordinate deviation on the left and right of the patients with MoCA＜26,MMSE＜27,ADAS-Cog≥36 and CGIC-S＞1 was statistically higher than that of the patients with MoCA≥ 26,MMSE≥27,ADAS-Cog＜36 and CGIC-S≤1(P＜0.01).Correlation analysis displayed that the bilateral fusion error of patients was negatively correlated with MoCA and MMSE scores(r=-0.678,P＜0.01;r=-0.653,P＜0.01;r=-0.448,P＜0.01;r=-0.704,P＜0.01),and positively with ADAS-Cog,CGIC-S,SDS and SAS scores(r=0.586,P＜0.01;r=0.501,P＜0.01;r=0.572,P＜0.01;r=0.601,P＜0.01;r=0.742,P＜0.01;r=0.667,P＜0.01;r=0.463,P＜0.01;r=0.381,P＜0.01).Conclusion In PD treatment,electrode fusion error during STN-DBS is significantly correlated with improvement of depression and cognitive score,which can be used as one of the important evidence for predicting clinical effectiveness.In the future,according to the intraoperative error,auxiliary treatment can be carried out timely and effectively to guide further clinical treatment.

In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H₂O₂-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H₂O₂, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H₂O₂ levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE^‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H₂O₂-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

Objective:To investigate the effects of vagus nerve stimulation on postoperative cognitive dysfunction and the role of hippocampal insulin growth factor 1 signaling pathway in aged mice.Methods:Seventy-five clean-grade C57 mice of both sexes, aged 21-23 months, weighing 28-34 g, were divided into 5 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O), operation + vagus nerve stimulation group (group O+ V), operation + IGF-1 siRNA group (group O+ I) and operation + vagus nerve stimulation + IGF-1 siRNA group (group O+ V+ I). Group O underwent exploratory laparotomy.Group O+ V received a 30-min electrical stimulation of the vagus nerve (intensity 0.5 mA, frequency 20 Hz, time 30 s, 6 times, interval 5 min) after the end of exploratory laparotomy.Group O+ I underwent exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Group O+ V+ I underwent electrical vagus nerve stimulation after exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Morris water maze tests were performed on 14-18 days after operation.On day 7 after operation, the mice were sacrificed and the hippocampus was obtained for determination of the expression of Bax, ionized calcium-binding adapter molecule 1 (Iba-1), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF1R), phosphorylated IGF1R (p-IGF1R), interleukin-1beta (IL-1β) and activated caspase-3 by Western blot. Results:Compared with group S, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened on days 16-18 after operation, the frequency of crossing the platform was increased, the time spent in the target quadrant was prolonged, the expression of IGF-1 and p-IGF1R was up-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was down-regulated in group O+ V ( P<0.05), and no significant change was found in the parameters mentioned above in group O+ I ( P>0.05). Compared with group O+ V, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O+ V+ I ( P<0.05). There was no significant difference in the expression of IGF1R among the four groups ( P>0.05). Conclusions:Vagus nerve stimulation can reduce postoperative cognitive dysfunction, and the mechanism is related to activation of IGF-1 signaling pathway and reduction of hippocampal neuroinflammation and neuronal apoptosis in aged mice.

Objective:To evaluate the effects of intranasal administration of glial cell line-derived neurotrophic factor (GDNF) on postoperative cognitive dysfunction in aged rats.Methods:Forty healthy Sprague-Dawley rats of both sexes, aged 21-23 months, weighing 480-600 g, were divided into 4 groups ( n=10 each) using a random number table method: sham operation group (group S), operation group (group O), intranasal administration of low-dose GDNF group (group G1) and intranasal administration of high-dose GDNF group (group G2). Rats underwent exploratory laparotomy under anesthesia with chloral hydrate in O, G1 and G2 groups, while the rats in group S only received sham operation.The rats in group G1 and group G2 were intranasally treated with GDNF 25 and 50 μg (in 25 μl of PBS), respectively, and PBS 25 μl was nasally administered in group S and group O every day for 3 consecutive days after operation or sham operation.Morris water maze test was performed on days 3-7 after surgery, and then the rats were sacrificed, and hippocampal tissues were removed for determination of the expression of GDNF, high mobility group box 1 (HMGB1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), activated caspase-3 and Bax (by Western blot). Results:Compared with group S, the escape latency was significantly prolonged on days 5-7 after operation, the number of crossing the platform was reduced, time spent in the target quadrant was shortened, expression of GDNF was down-regulated, and expression of IL-1β, TNF-α, HMGB1, activated caspase-3 and Bax in hippocampi was up-regulated in group O, and the number of crossing the platform was reduced, time spent in the target quadrant was shortened, and expression of IL-1β and TNF-α was up-regulated in G1 and G2 groups ( P<0.05). Compared with group O, the escape latency was significantly shortened on days 5-7 after operation, the number of crossing the platform was increased, time spent in the target quadrant was prolonged, expression of GDNF was up-regulated, expression of TNF-α, HMGB1, activated caspase-3 and Bax in hippocampi was down-regulated in G1 and G2 groups, and IL-1β in hippocampi was down-regulated in group G1 ( P<0.05). Compared with group G1, the expression of TNF-α in hippocampi was down-regulated ( P<0.05), and no significant change was found in the other parameters mentioned above in group G2 ( P>0.05). Conclusions:Intranasal administration of GDNF can improve postoperative cognitive dysfunction, and the mechanism may be related to inhibiting neuroinflammatory responses and neuroapoptosis in aged rats.

Objective:To obtain the parameters associated with hematoma morpholoy by finite element analysis(FEA) and investigated their performance on predicting and diagnosis hematoma expansion(HE) in patients with spontaneous intracrebral hemorrhage(SICH).Methods:Patients with SICH who met research criteria were retrospective enrolled between June 2015 and December 2017. Clinical parameters on admission were collected, Perform 2 independent methodology on same patient to analysis the hematoma shape base on computed tomography(CT): Clinical routine method that performed by clinical investigator to identified margin irregularity of hematoma by CT ,and calculated the volume of hematoma by simplify Tada formula(ABC/2);The FEA method performed by FEA investigator and gain the hematoma 3 dimensional morphology and variables, include Volume, Surface area, and The quantity of triangles per square milimet surface(TQOT/mm 2). The HE was defined as volume enlargement of >33% compared with that on addmission. All patients were divided into HE and none HE group ,respectively, ABC/2 and FEA generated thire own HE and none HE group as different volume calcuation. The HE risk factors of ABC/2 and FEA were assessed in univariate and multivariable Logistic regression models. and the risk fators diagnosis value for HE were determined by the receiver operating characteristic(ROC) curves. Results:Total of 127 patients were enrolled, The mean time of symptom onset to hospital admitted was 3.08±1.34 h. There were 34(26.77%) cases HE identifed by ABC/2 and 31(24.41%)by FEA. Althought there are significant different (pearson χ2=53.66, P<0.01) of HE identification between ABC/2 and FEA, the 2 methods has moderate consistency (Kappa=0.65). All patients’ hematoma 3D reconstruction were performed by FEA and general observation show that TQOT/mm 2 most likely correlate to irregularity of hematoma 3D shape. Multivariable Logistic regression models indicated that ICH score( OR=1.79, 95% CI:1.19~2.68)was independent HE risk factor for ABC/2, respectively, TQOT/mm 2≥1.95/mm 2 ( OR=16.99,95% CI:5.98~48.33)and Ultraearly Hematoma Growth,(uHG) ( OR=1.05, 95% CI:1.01~1.09)were independent HE risk factor for FEA. With ROC analysis, both the ICH score of ABC/2 and uHG of FEA have low HE predictive and diagnosis value ,the area under the curve (AUC) were 0.64 and 0.67 respectively. However, TQOT/mm 2 was found to have excellent diagnosis value (AUC:0.9), sensitivity and specificity were 77% and 83% when the cut-off value was 1.95. Panel parameter model (TQOT/mm 2+uHG) was not be found to have a significant higher AUC than single parameter on FEA and the clinical routine parameters panel model (ICH +SB P>180 mmHg on addmission) have a unacceptable AUC(<0.7) as well as single parameters. Conclusions:Hematoma shape could be reconstructed and analysis by FEA and TQOT/mm 2 was likely relevance to hematoma morphology. TQOT/mm 2≥1.95 was indicate to have a better HE predicting and diagnosis value than any other risk factors and clinical parameters panel models in our reaserch.

OBJECTIVE: To analyze the characteristics of cervical microecology in late reproductive-age women with cervical lesions and explore new methods for preventing cervical lesions. METHODS: Cervical smears were obtained from a total of 147 women of late reproductive age, including 24 with high-risk HPV infection (HR-HPV), 27 with low-grade squamous intra-epithelial lesions (LSIL), 36 with high-grade squamous intra-epithelial lesions (HSIL), 35 with cervical cancer (CC) and 25 healthy women. llumina MiSeq sequencing of V3-V4 region of the 16S rRNA gene amplicons was used to characterize the vaginal microbiota of the women. OTUs analysis of the valid data was performed, and the α-diversity (Chao1, Simpson's Index and Shannon Index) and β-diversity (T-test, weighted UniFrac β diversity, and MetaStat analysis) were evaluated. RESULTS: Dilution curve and species accumulation boxplot validated the quality of the samples. OTUs analysis of the 5 groups demonstrated that cervical bacterial genus consisted primarily of CONCLUSIONS The abundance of
Female ; Humans ; Microbiota ; Papillomaviridae ; Papillomavirus Infections ; RNA, Ribosomal, 16S/genetics* ; Uterine Cervical Neoplasms ; Vaginal Smears

Objective To analyze the situation and changing trend of free medication service in Beijing from 2013 to 2020, and to propose policies and service improvement measures. Methods A retrospective survey was conducted in Beijing to collect and analyze the service subjects, service process, drug catalog, fiscal investment and patient participation of free medication in each district in recent years. Results Among the 16 districts of Beijing, 81.25% of the districts included the patients listed in Item (2) of Paragraph 2 of Article 30 of the Mental Health Law into the scope of free medication, and 75% of the districts broke the restriction that the service targets were registered residents in Beijing. 56.25% of the districts provided a variety of free medication modes, and 81.25% of the districts provided a mode of nearby community service. The catalog of free medications in various areas was still based on the Beijing catalog, and only 18.75% of the districts supplemented the list. In 2020, the total investment of free medicines and subsidies was 88.3768 million RMB, and the per capita investment was 1 616.02 RMB. The total cost showed an increasing trend year by year. From 2013 to 2020, the difference of per capita annual financial investment in drugs and subsidies was statistically significant (F=9.248, P<0.001). The per capita cost basically showed an increasing trend year by year except for individual years. In 2020, 54,688 patients participated in the free medication service in Beijing, and the participation rate was 67.23%. From 2013 to 2020, the difference of annual participation rate of patients was statistically significant (χ²=37098.759, P<0.001), and the number and proportion of patients increased year by year. Conclusion The practice of the district level has proved feasible to expand the scope of free medication service and to optimize the service process, which should be paid more attention in the future. With the continuous advancement of policies and services, the level of patient participation in various areas will tend to be relatively balanced after rising year by year.

Objective To evaluate the in vitro antifungal activity of 4 antifungal agents alone or in combination against Exophiala dermatitidis (E.dermatitidis) biofilms.Methods E.dermatitidis biofilms were prepared by using a modified 96-well plate-based method.The in vitro antifungal activity of amphotericin B,voriconazole,itraconazole and caspofungin alone or in combination against E.dermatitidis biofilms were investigated via the broth microdilution checkerboard technique.Results The sessile minimum inhibitory concentration ranges resulting in 50％ (SMICS0) and 80％ inhibition (SMIC80) of E.dermatitidis biofilms were all ＞ 32 mg/L for itraconazole,voriconazole and caspofungin,and the SMIC50 and SMIC80 ranges of amphotericin B were 1-2 mg/L and 4-8 mg/L respectively.The combination of amphotericin B with voriconazole showed synergistic inhibitory effects against E.dermatitidis biofilms,while the combination of amphotericin B with itraconazole or caspofungin,as well as the combination of voriconazole with caspofungin,revealed no synergistic effects.No antagonistic effect was observed in any of the combinations.Conclusion Amphotericin B appears more active against E.dermatitidis biofilms,and the combination with voriconazole can enhance the anti-biofilm effects against E.dermatitidis biofilms.