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 explore the causal relationship between 46 phenotypes ( including 15 seropositive case- control phenotypes and 31 quantitative antibody-measurement phenotypes) and ulcerative colitis( UC) using two- sample bidirectional Mendelian randomization( TSMR) . Methods: Single nucleotide polymorphisms ( SNPs) sig- nificantly associated with the relative abundance of the 46 antibody sera were extracted as instrumental variables ac- cording to preset thresholds . Summary statistics for UC were obtained from the OPEN GWAS database ( n = 47 745) . MR-Egger regression , weighted median method ( WME) , inverse variance weighting ( IVW) , the simple mode method (SM) , and weighted multitude method (WM) were used to estimate the causal relationship between antibody levels and UC , primarily using the IVW method . The results were assessed according to the effect indica- tor dominance ratios (OR) and 95% confidence intervals (CI) . Sensitivity analysis , heterogeneity test , gene plei- otropy test , and outlier test (MR-PRESSO) were combined to verify the stability and reliability of the results , and the causal association study was performed again using reverse Mendelian randomization(MR) . Results : IVW re- sults showed that Epstein-Barr( EB) virus EA-D antibody levels ( OR = 0. 806 , 95% CI = 0. 693 - 0. 939 , P < 0. 01) , Epstein-Barr virus EBNA-1 antibody levels ( OR = 1 . 870% , 95% CI = 1 . 480 - 2. 360 , P < 0. 000 1) , Anti-polyomavirus 2 IgG seropositivity (OR = 0. 570 , 95% CI = 0. 435 - 0. 746 , P < 0. 000 1) were associated with UC . The inverse MR analysis revealed a causal effect on anti-polyomavirus 2 IgG seropositivity , and none of the a- bove revealed genetic pleiotropy or significant heterogeneity of IVs . Conclusion EB virus EBNA-1 antibody levels are positively associated with the risk of UC , while EB virus EA-D antibody levels and anti-polyomavirus 2 IgG se- ropositivity are negatively associated with the risk of UC , indicating that they are protective factors for UC .

ObjectiveTo study the relationship between qi stagnation constitution and suboptimal health status (SHS) or lifestyle.MethodsFrom 2012 to 2013, we conducted a cross-sectional survey of 24 159 Chinese individuals aged 12–80 years. The qi stagnation constitution was assessed using the Constitution in Chinese Medicine Questionnaire. Health status was evaluated through medical records and the Subhealth Measurement Scale V1.0 (SHMS V1.0). Health-promoting lifestyles were measured using the Health-Promoting Lifestyle Profile II (HPLP-II).ResultsOf the 24 159 participants, 16.1% and 15.2% were classified as “always” and “sometimes” having the qi stagnation constitution, respectively. Those classified as “rarely” having the qi stagnation constitution scored higher on both the HPLP-II and SHMS V1.0. The participants classified as “always” having the qi stagnation constitution showed a significant association with SHS or disease compared to other imbalanced constitutions. Those in the “always” category were approximately 21 times more likely to be classified as having SHS (odds ratio [OR]: 21.17, 95% confidence interval [CI]: 15.74–28.45), whereas those in the “sometimes” category were approximately six times more likely (OR: 5.89, 95% CI: 5.04–6.90). Accordingly, the qi stagnation constitution score was significantly associated with the diagnosis of SHS, with an area under the curve of 0.77 (P .001). A score of 18.75 yielded the highest Youden Index (0.407), with a sensitivity of 60.5% and a specificity of 80.3%. Significant associations were observed between health-promoting lifestyles and qi stagnation constitution severity in an ordinal regression analysis (P .001). Protective factors included stress management (OR: 1.59), self-actualization (OR: 1.57), and exercise (OR: 1.36). In contrast, poorer interpersonal relationships (OR: 0.79), greater health responsibilities (OR: 0.86), and poorer nutrition (OR: 0.91) were associated with increased severity.ConclusionModulating the qi stagnation constitution through lifestyle interventions may help prevent the progression of SHS to disease, which aligns with core preventive principles in traditional Chinese medicine.

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.

Aim To investigate whether elevated monocyte to lymphocyte ratio(MLR)is associated with the in-hospital mortality risk in elderly patients with acute myocardial infarction(AMI).Methods The medical history of 1 550 elderly patients with AMI hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Dalian Medical University from December 2015 to December 2021 was retrospectively collected,including 132 patients who died during hospitalization.It mainly includes gender,age,height,body weight,blood routine,lipid related indicators,fast-ing blood glucose(FBG),myocardial enzyme,type of myocardial infarction,estimated glomerular filtration rate(eGFR),in-hospital outcomes,prevalence of heart failure,diabetes,hypertension,and use of statins and antiplatelets during hospi-talization.According to ROC curve analysis,patients with MLR＞0.342 were defined as high MLR group(n=699),whereas patients with MLR≤0.342 were defined as low MLR group(n=851).Results The age,white blood cell count,monocyte count,MLR,cardiac troponin I(cTnI),FBG,eGFR＜60 mL/(min·1.73 m2),male patients,heart failure,and proportion of all-cause deaths occurred during hospitalisation were higher in the high MLR group than those in the low MLR group(P＜0.05),body mass index(BMI),lymphocyte count,low density lipoprotein cholesterol(LDLC),eGFR＞60 mL/(min·1.73 m2),hypertension,and use of antiplatelet agents were lower in the high MLR group compared to the low MLR group(P＜0.05).Multivariate Logistic regression results showed that high MLR was independently asso-ciated with the in-hospital mortality risk in elderly AMI patients(OR=1.812,95％CI:1.106～2.969,P=0.018).The results of ROC curve analysis showed that the predictive ability of MLR combined with cTnI or FBG would be significantly improved,and the area under ROC curve was 0.789 and 0.739,respectively.Restrictive cubic spline(RCS)analysis results indicated a linear dose-response relationship between MLR and in-hospital outcomes in elderly AMI patients.Conclusion Elevated MLR is independently associated with the in-hospital mortality risk in elderly AMI patients,and cli-nicians can consider using MLR indicators in daily diagnosis for risk stratification and related treatment of such patients to improve their short-term prognosis.

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.

The basic pathological change of diabetic macroangiopathy is atherosclerosis （AS）， which is mainly associated with vascular endothelial cells （VECs） injury， oxidative stress， glucose and lipid metabolism disorders， hemorheological abnormalities， and endoplasmic reticulum stress. The injury and dysfunction of VECs are the initiating factors of diabetic macroangiopathy. Autophagy is a subcellular self-protection mechanism that regulates basic intracellular metabolism through lysosome-mediated degradation of proteins and damaged organelles to maintain homeostasis. Insufficient autophagy of VECs leads to enhanced inflammation， apoptosis， and oxidative stress of VECs， which promotes AS. According to the theory of traditional Chinese medicine （TCM）， diabetic macroangiopathy corresponds to the syndrome of internal deficiency and pathogen invasion， with Qi deficiency and stagnation as the key pathogenesis. Qi deficiency is the root cause， and Qi stagnation is the manifestation. The disease occurs with the initial cause of nutrient-defense disharmony and instability of vessels， the main cause of the deficiency of kidney Qi and the lack of source for generation and transformation， the internal cause of Qi and blood loss in the viscera and the stagnation of Qi， blood， and fluid， and the superficial cause of the stagnation of pathological products and the damage of vessels. Autophagy is a microscopic manifestation of Qi， which has the function of dispelling pathogens and maintaining homeostasis. Insufficient autophagy of VECs leads to Qi deficiency and stagnation， and the gradual deficiency and heavy stagnation of Qi lead to insufficient autophagy， which form a vicious cycle. Modern research has demonstrated that regulating the autophagy of VECs is the main way to prevent and treat AS， and TCM can exert the therapeutic effect in a multi-target and multi-pathway manner. Therefore， based on the theory of Qi deficiency and stagnation， the method of tonifying deficiency of and removing stagnation can be adopted to select prescriptions for regulating the autophagy of VECs and treating AS， which can slow down the procession of diabetic macroangiopathy.

Diabetic nephropathy （DN） is one of the serious and common microvascular complications of diabetes mellitus （DM） and the main cause of end-stage renal disease （ESRD）. Endoplasmic reticulum stress （ERS） is a common stress defense mechanism in eukaryotic cells. In the ERS state， cells activate the unfolded protein response （UPR） to enhance the folding of unfolded proteins and the degradation of misfolded proteins， so as to restore the normal physiological function of the endoplasmic reticulum and avoid cell damage. However， excessive or chronic persistent ERS can induce apoptosis， inflammation， oxidative stress and other pathways to eventually cause cell damage. In recent years， a large number of studies have confirmed that ERS is closely associated with the occurrence and development of DN. In the case of DN， ERS is involved in the damage or protection of podocytes， glomerular mesangial cells， renal tubular epithelial cells， and glomerular endothelial cells. The regulation of ERS has become one of the hotspots in the prevention and treatment of DN and has received extensive attention in the field of traditional Chinese medicine. This paper systematically expounds the role of ERS in the occurrence and development of DN and summarizes the ERS-targeted regulation of DN by traditional Chinese medicine， with a view to providing certain research ideas for the prevention and control of DN with traditional Chinese medicine.

The basic pathological change of diabetic macroangiopathy is atherosclerosis， and the metabolism legacy effect of hyperglycemia will cause continuous damage to the large vessels. Oxidative stress is a common mechanism for diabetes and its chronic complications and it is also the basis of the metabolism legacy effect which keeps damaging the large vessels. Anti-oxidant therapy can delay the course of diabetic macroangiopathy. According to the theory of traditional Chinese medicine （TCM）， the pathogenicity of hidden pathogen is concealing， lingering， and refractory. On the basis of the syndrome and treatment of collateral diseases， vessel-collateral theory， and hidden pathogen theory of TCM， the pathological changes of diabetic macroangiopathy are summarized as pathogen concealment-accumulation of sugar and lipids leading to phlegm and blood stasis-accumulation of toxins-damage to vessels and collaterals-hardening vessels. The core pathogenesis is the hidden pathogen damaging the collaterals， and the basic pathological change is vessel hardening. The toxins of sugar， lipid， phlegm， and stasis are the pathological products and the key to be treated. According to this theory， the medicinal materials with the functions of activating blood to dredging collaterals， resolving phlegm to clearing collaterals， Promoting qi to unblocking collaterals and removing toxins to shunting collaterals can be selected for prescription. These medicinal materials can inhibit the generation of reactive oxygen species， affect the oxidase activity， and enhance the antioxidant capacity， thereby regulating the oxidative stress response， protecting the vascular endothelial function， reducing the damage of the large blood vessels， and slowing down the progression of the disease. Such therapy is of great significance in clinical practice and research， providing a new idea for the prevention and treatment of diabetic macroangiopathy.

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.