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.

The application of pesticides(mostly insecticides and fungicides)during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea.Thus,it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits.However,the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues.In this study,nine types of lateral flow immunochromatographic strips(LFICSs)were developed to detect the pesticides of interest(fenpropathrin,chlorpyrifos,imidacloprid,thiamethoxam,acet-amiprid,carbendazim,chlorothalonil,pyraclostrobin,and iprodione).To reduce the interference of tea substrates on the assay sensitivity,the pretreatment conditions for tea samples,including the extraction solvent,extraction time,and purification agent,were optimized for the simultaneous detection of these pesticides.The entire testing procedure(including pretreatment and detection)could be completed within 30 min.The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.

Atopic dermatitis (AD) is a chronic inflammatory skin condition. Natural products have gained traction in AD treatment due to their accessibility, low toxicity, and favorable pharmacological properties. However, their application is primarily constrained by poor solubility, instability, and limited permeability. The transdermal drug delivery system (TDDS) offers potential solutions for transdermal delivery, enhanced penetration, improved efficacy, and reduced toxicity of natural drugs, aligning with the requirements of modern AD treatment. This review examines the application of hydrogels, microneedles (MNs), liposomes, nanoemulsions, and other TDDS-carrying natural products in AD treatment, with a primary focus on their effects on penetration and accumulation in the skin. The aim is to provide valuable insights into the treatment of AD and other dermatological conditions.
Animals ; Humans ; Administration, Cutaneous ; Biological Products/pharmacokinetics* ; Dermatitis, Atopic/drug therapy* ; Drug Delivery Systems ; Hydrogels/chemistry* ; Skin/metabolism* ; Skin Absorption

Objective:To describe the clinical features and prognosis of congenital anomalous origin of coronary artery(AOCA) in children to increase our understanding of the disease.Methods:This retrospective study included children diagnosed with AOCA using computed tomography coronary angiography(CTCA) admitted to the Department of Cardiology, Beijing Children′s Hospital, Capital Medical University, from January 1, 2014 to December 31, 2019.The clinical presentations, laboratory results, imaging analyses, treatments, and prognoses of these patients were analyzed.Results:A total of 208 children, including 105 boys and 103 girls, we evaluated the ages(9.03±4.18)years old with AOCA.Of these, 157 cases(75.5%) presented with cardiac symptoms, such as chest tightness, palpitations, dizziness, syncope, fatigue, and decreased endurance.Three cases(1.4%) had atypical symptoms of paroxysmal crying, dyspnoea and cyanosis, and 48 cases(23.1%) were asymptomatic.Levels of serological markers of myocardial injury were elevated in 59 cases(28.4%), and 140 cases(67.3%) had predominant ST-T abnormalities on electrocardiograms.Transthoracic echocardiography identified 27 cases (13%) with cardiac enlargement and ten cases(4.8%) with left ventricular systolic dysfunction.There were 126 cases(60.6%) with the anomalous origin of the left coronary artery revealed by CTCA, 50 cases(24.0%) with the anomalous origin of the right coronary artery and 32 cases(15.4%) with bilateral coronary arteries of anomalous origin.Five children underwent surgical treatment, and the remaining 203 children were treated conservatively with drugs.The whole group was successfully treated, and no death case was recorded during the follow-up period.Conclusion:AOCA may cause different degrees of myocardial ischemia.Diverse clinical presentations and diagnostic limitations of transthoracic echocardiography often lead to missed diagnosis or misdiagnosis.In contrast, CTCA has high diagnostic accuracy and can be used to identify the location and course of the coronary ostia.Hence, the management of AOCA should be tailored on a case-to-case basis, taking into consideration of the specific type of coronary origin, with surgical intervention being warranted if necessary.

Pathological anxiety is among the most difficult neuropsychiatric diseases to treat pharmacologically, and it represents a major societal problem. Studies have implicated structural changes within the prefrontal cortex (PFC) and functional changes in the communication of the PFC with distal brain structures in anxiety disorders. Treatments that affect the activity of the PFC, including cognitive therapies and transcranial magnetic stimulation, reverse anxiety- and fear-associated circuit abnormalities through mechanisms that remain largely unclear. While the subjective experience of a rodent cannot be precisely determined, rodent models hold great promise in dissecting well-conserved circuits. Newly developed genetic and viral tools and optogenetic and chemogenetic techniques have revealed the intricacies of neural circuits underlying anxiety and fear by allowing direct examination of hypotheses drawn from existing psychological concepts. This review focuses on studies that have used these circuit-based approaches to gain a more detailed, more comprehensive, and more integrated view on how the PFC governs anxiety and fear and orchestrates adaptive defensive behaviors to hopefully provide a roadmap for the future development of therapies for pathological anxiety.
Anxiety ; Anxiety Disorders/therapy* ; Fear/psychology* ; Humans ; Neural Pathways ; Prefrontal Cortex

Objective:To investigate the effect of microRNA-146a (miR-146a) on apoptosis of human retinal microvascular endothelial cells (HRMECs) induced by high glucose and its possible molecular mechanism.Methods:HRMECs were cultured in vitro with 5.5 mmol/L D-glucose in the normal control group and 25 mmol/L D-glucose in the high glucose group for 48 hours, respectively.Normally cultured HRMECs were transfected by miR-146a mimics in the high glucose+ miR-146a mimics group or corresponding mimics control in the high glucose+ mimics control group by lipofection and cultured with 25 mmol/L D-glucose for 48 hours, respectively.Real-time fluorescent quantitative polymerase chain reaction (PCR) was performed to detect the expression level of miR-146a.MTT assay and flow cytometry were used to detect the activity and apoptosis of HRMECs, and Western blot was employed to detect the expression levels of apoptosis-associated protein B-cell lymphoma factor-2 (Bcl-2), Bcl-2 related X protein (Bax) and nuclear factor-κB (NF-κB) signaling-related proteins NF-κB p65 and p-NF-κB p65. Results:The relative expression levels of miR-146a were 1.00±0.10, 0.22±0.02, 0.21±0.02 and 0.88±0.09, and the cell viability was (100.00±10.06)%, (68.41±6.67)%, (67.91±6.74)% and (90.46±8.97)%, and the apoptosis rates were (3.11±1.02)%, (27.28±3.56)%, (27.44±4.03)% and (7.29±2.11)% in the normal control group, high glucose group, high glucose+ mimics control group and high glucose+ miR-146a mimics group, respectively.The relative expression levels of miR-146a and the cell viability were significantly lower, and the cell apoptosis rate was significantly higher in the high glucose group than those in the normal control group, with statistical significant differences (all at P<0.05). The relative expression levels of miR-146a and the cell viability were significantly higher, and the cell apoptosis rate was significantly lower in the high glucose+ miR-146a mimics group than those in the high glucose group and the high glucose+ mimics control group, and the differences were statistically significant (all at P<0.05). The relative expression levels of Bax and p-NF-κB p65 protein were significantly higher, the relative expression level of Bcl-2 protein was significantly lower in the high glucose group than those in the normal control group, showing statistically significant differences (all at P<0.05). The relative expression levels of Bax and p-NF-κB p65 protein were significantly lower, and the relative expression level of Bcl-2 protein was significantly higher in the high glucose+ miR-146a mimics group than those in the high glucose group and the high glucose+ mimics control group, and the differences were statistically significant (all at P>0.05). There was no significant difference in the relative expression of NF-κB p65 protein among the groups ( F=0.106, P=0.955). Conclusions:Overexpression of miR-146a may inhibit the apoptosis of HRMECs induced by high glucose, and its mechanism may be related to the inhibition of NF-κB signaling pathway activation.

Objective:To evaluate the heart hemodynamics in fetuses with premature ductus arteriosus constriction or closure using fetal heart quantification (FHQ).Methods:The clinical data of 50 singleton fetuses with ductus arteriosus constriction ( n=35) or ductus arteriosus closure ( n=15) who underwent echocardiography in Department of Ultrasound, Beijing Anzhen Hospital were retrospectively analyzed, from May 2013 to January 2020. Fifty healthy singleton fetuses were randomly selected as the control group. The ductus arteriosus diameter (DA), pulsatility index (PI), diameter of the left atrium(LA) and right atrium(RA), diameter of the left ventricle (LV) and right ventricle (RV), tricuspid regurgitation/right atrium area ratio (TR/RA Ratio), pressure gradient of tricuspid regurgitation (PG of TR), and heart/chest ratio were measured using conventional fetal echocardiography; the correlations among the parameters were analyzed. Speckle-tracking analysis was used to analysis and compute the LV and RV global spherical index (GSI), fractional area change (FAC) and global strain (GS), the LV ejection fraction(EF) and stroke volume (SV). These variables and their correlations were compared and analyzed. Results:Compared with the control group, the GS and FAC of the LV and RV in the ductus arteriosus constriction or closure groups were lower ( P<0.05) while the LV-SV was higher ( P<0.05). The FAC, GS, and EF values of the LV were higher in the premature ductus arteriosus closure group than in the ductus arteriosus constriction group ( P<0.05), while the RV-FAC was lower ( P<0.05), the RV-GS and LV-SV showed no significant changes ( P>0.05). Correlation analyse showed that the PI was positively correlated with DA( r=0.364, P<0.05); the PG of TR was negatively correlated with DA( r=-0.414, P<0.05); the TR/RA Ratio was negatively linearly correlated with PI( r=-0.388, P<0.05), and positively correlated with RV/LV Ratio ( r=0.369, P<0.05); the other parameters were not significantly correlated with the DA or PI ( P>0.05). Conclusions:Fetal heart hemodynamics in the premature ductus arteriosus constriction or closure groups change significantly, FHQ can provide valuable information for the evaluation of the fetal heart with ductus arteriosus constriction or closure.

During the COVID-19 epidemic, there have been many misconceptions concerning vertical transmission between the mother and fetus/baby, which has caused much discussion and controversy. However, there is no strong evidence to indicate that this novel coronavirus could be vertically transmitted from infected mothers to their fetuses/infants. Several easily confused concepts are clarified in this paper, including vertical transmission, intrauterine transmission, mother-to-infant transmission, intrapartum or postpartum transmission. Well-designed protocols and a disciplined research team are essential for both basic and clinical research, in order to contribute to obtaining more scientific evidence for better understanding of the characteristics of this novel coronavirus. Proper handling and disposal of the body fluids and tissue are critical for safety. We highlight the significant value of relevant research, and suggest future research directions, such as investigating the impact of COVID-19 in different trimesters. Furthermore, China has the most experience of treating pregnant women exposed to the COVID-19 virus, and it would be a great service to the rest of the world, for all centers in China to collaborate to report this collective experience.

Objective To explore the CT and MRI imaging and clinicopathological features of extranodal NK/T cell lymphoma (NK/TCL). Methods Sixty-six patients with NK/TCL diagnosed from 2002 June to 2016 April in Beijing Tongren Hospital with intact CT and/or MRI imaging results were enrolled in this study. All the patients had tailed clinical information and follow-up. The imaging and clinicopathological features were analyzed retrospectively and their prognostic value on overall survival was analyzed. Results There were 49 males and 17 females with median age of 42 years. The median follow-up time was 18 months. The cases showed surrounding invasions including 10 cases (15.2 %) in soft palate, 5 cases (7.6 %) in hard palate, 2 cases(3.0 %) in tonsil, 8 cases(12.1 %) in upper lip, 13 cases(19.7 %) in maxillofacial soft tissue, 9 cases (13.6 %) in eyelid, 10 cases (15.2 %) in orbital, 3 cases (4.5 %) in maxilla, 6 cases (9.1 %) in pterygopalatine fossa,6 cases(9.1 %)in infratemporal fossa,3 cases(4.5 %)in skull base, 3 cases(4.5 %) in eyeball and 2 cases (3.0 %) in brain tissue. Kaplan-Meier survival analysis found that the 2-year overall survival rates of the patients with the involvement of hard palate, upper lip, maxillofacial soft tissue, eyelid, orbital, maxillary, eyeball and brain organizer were lower than those of the patients without the involvement of these sites(χ2values were 4.470,4.041,4.456,13.933,8.986,4.000,44.121,6.527,16.822,respectively, all P< 0.05). Further multivariate Cox regression analysis showed that maxilla and brain involvement were independent adverse factors (RR=34.717, 95 % CI 3.404-354.035, P=0.003; RR=37.545, 95 % CI 3.188-442.187, P= 0.004). Conclusions MRI and CT examinations are of great value in diagnosis and prognostic assessment of NK/TCL. Clinicians can make correct and timely diagnosis by comprehensive clinical, radiological and pathological features and can make a detailed clinical assessment to give patients appropriate treatment,thus improving the outcome of the NK/TCL patients.

Objective: To explore the application values of prenatal ultrasound, vascular cast in the diagnosis of fetal aortic arch and its branches anomalies and to analyze the genetic characteristics by gene detection. Methods: Twenty-two cases of the vascular cast specimens of the fetal aortic arch and its branches anomalies were analyzed and studied by comparing with their prenatal ultrasonography. Then the characteristics of each type of fetal aortic arch and its branches anomalies, the missed diagnosis and misdiagnosis were summarized and the results of their gene detection were also analyzed. Results: The 22 cases of fetal aortic arch and its branches anomalies were as follows: 2 cases of double aortic arch showed the ascending aorta was divided into two branches after converging as the descending aorta. Three cases were left aortic arch with aberrant right subclavian artery. Twelve cases were right aortic arch: 8 cases were right aortic arch with mirror-image branching, 3 cases were right aortic arch with aberrant left subclavian artery, 1 case was right aortic arch with isolated left subclavian artery. Of the 8 right aortic arch with mirror-image branching, 3 cases of left arterial duct showed the vertical walking between the fusion site of the left innominate artery and the pulmonary artery. Right aortic arch with aberrant left subclavian artery with arterial duct showed "U" shaped vascular ring. Five cases were other types, including 2 cases of the coarctation of aortic arch, 1 case of interrupted aortic arch, 1 case of pulmonary artery sling, and 1 case of abnormal origin of right pulmonary artery. The ultrasonic missed diagnosis were the 6 deformities: 3 cases of arterial duct and 3 cases of aberrant subclavian artery. The ultrasonic misdiagnosis were the 5 deformities: 2 cases of arterial duct location, 1 case of aberrant subclavian artery, 1 case of isolated left subclavian artery, and 1 case of the coarctation of aortic arch. Genetic test results: In the 18 cases of the genetic detection, 2 cases were positive, 1 case was 22q11.2 microdeletion syndrome and 1 case was carrying KMT2D gene variant. Conclusions There are various kinds of fetal aortic arch and its branches anomalies, which are often associated with intracardiac malformations and venous branches variation. And prenatal ultrasound is of great value in diagnosing them.Vascular cast can visually display their characteristic changes, which is helpful to improve the differential diagnosis of the different aortic arch and its branches anomalies. The detailed genetic detection can improve the further understanding of its etiology.