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.

Purpose To investigate the application value of cardiac magnetic resonance tissue tracking imaging in assessing early heart failure(HF)in plateau environment.Materials and Methods Thirty male SD rats were randomly divided into 10 in the control group and 20 in the experimental group.The rats in the experimental group were transported to the Qinghai Plateau laboratory(average altitude 4 250 metre)for eight weeks of exposure,and then divided into the plateau hypoxia group and the plateau HF group,and the HF group was treated with 5 mg/ml Isoprenaline 10 mg/(kg·d)subcutaneously for 14 consecutive days to establish a HF rat model.The rats were then transported back to the plains(average elevation 500 metre)for 7T cardiac magnetic resonance movie sequence scanning.Cardiac function parameters and myocardial strain parameters were obtained using CVI 42 software.Myocardial pathological changes were detected using HE staining and Masson trichrome staining.Serum levels of malondialdehyde and glutathione peroxidase were detected by enzyme-linked immunosorbent assay.Western blot and PCR were used to detect the expression of nuclear factor-E2-related factor 2(NRF2)and heme oxygenase 1(HO-1)in myocardial tissues.Results Left ventricular ejection fraction was reduced in the HF group compared with the control group[(67.06±4.66)%vs.(61.91±2.11)%;F=4.149,P=0.037],and overall left ventricular circumferential strain was significantly reduced in the HF group compared with the control group[(-24.60±0.81)%vs.(-20.16±1.86)%;F=12.241,P=0.001],and pathologic staining showed necrosis as well as interstitial fibrosis in cardiomyocytes.Enzyme-linked immunosorbent assay results showed decreased glutathione peroxidase levels in the HF group[(1 079.94±70.58)U vs.(311.99±39.47)U;F=209.294,P=0.001]and increased malondialdehyde in the HF group compared with those in the control group[(7.24±2.48)μmol/L vs.(53.28±4.51)μmol/L;F=156.39,P=0.010).Western blot results showed significantly lower NRF2 and HO-1 expression in myocardial tissues of the HF group compared with those in the control group(1.00±0.00 vs.0.52±0.13;F=26.607,P=0.001).PCR results showed significantly lower NRF2 and HO-1 mRNA expression in myocardial tissues of the HF group compared with those in the control group(1.19±0.16 vs.0.31±0.07;F=84.784,P=0.010).Conclusion Magnetic resonance tissue tracking imaging can be used for early assessment of HF caused by plateau environment.

Objective:To explore the correlation between the oxygenation index and the monitored parameters of lung injury view in ventilator,so as to provide a basis for monitoring the change of oxygenation index by the parameters of lung injury view.Methods:A total of 28 patients who received mechanical ventilation treatment and admitted to respiratory department of the First Affiliated Hospital with Nanjing Medical University from May 14 to September 30,2024 were selected.The monitored parameters of lung injury views of them during mechanical ventilation treatment with invasive ventilators were collected,including platform pressure(Pplat),driving pressure(ΔP),mechanical energy(Emech),ratio of tidal volume to ideal body weight(TVe/IBW),etc..Then,the data of oxygenation index were obtained.Finally,135 valid data were screened out.The 84 pieces of data with oxygenation index≤300mmHg were included in low oxygen group,and 51 data with oxygenation index>300mmHg were included in normal group.The correlations between oxygenation index and Pplat,ΔP,Emech,TVe/IBW were conducted by pairwise analysis.Results:In the low oxygen group,the oxygenation index was[(196.302±74.522)mmHg]significantly negative correlation with Emech[(12.686±5.401)J/min](ρ=-0.425,P<0.05),but not was significant correlation with Pplat,ΔP,and TVe/IBW(P>0.05).In the normal group,there were not significant correlations between the oxygenation index and Pplat,ΔP,Emech and TVe/IBW(P>0.05).There was a significant negative correlation between Emech and rank of oxygenation index(β=-0.389,P<0.05)in the low oxygen group.Conclusion:The visualization function of the Emech of the monitored parameters in lung injury view of ventilator can provide help for monitoring the changes of oxygenation index of patients in the low oxygen group,and can improve the oxygenation of patients by optimizing mechanical energy.However,it is necessary to balance the contradiction between ventilation intensity and protection for lung.

Objective To investigate the cellular characteristics in the development of retinal tumors induced by MY-CN overexpression,and to find the key proteins that play an important role in this process.Methods T-MYCN Y1 and Y2 cells cultured in vitro for 1 year and 2 years were selected for the experiment.The WERI-RB-1 cell line obtained from Shanghai Cell Bank of Chinese Academy of Sciences was taken as the mature retinoblastoma(RB)control(WERI-Rb-1 group).Untreated normal human retinal tissues were used as the control group.Cells were inoculated into a 24-well plate at a density of 1 × 104 cells per well,and the cell morphology was observed under a microscope and images were collected.Cell count was performed on the 4th,8th and 12th day after inoculation.Immunofluorescence staining was employed to de-tect the expression of the proliferation marker Ki67 and cone cell marker L/M opsin in each group.Quantitative real time polymerase chain reaction(qRT-PCR)was utilized to assess the expression of MYCN,CCNB1,CDK1,SYK,and RXRγ in cells across all groups.Proteomics analysis was performed to detect variations in protein expression profiles across groups and to identify key regulatory genes.Subsequently,cell growth and proliferation were evaluated after OTX2 knockdown by lentiviruses.Results The growth curve showed that there were(59.17±4.01)× 104 cells in the T-MYCN Y1 group,(85.14±4.54)× 104 cells in the T-MYCN Y2 group and(100.73±1.99)× 104 cells in the WERI-Rb-1 group on the 12th day of in-vitro culture(all P＜0.05).Compared with those in the control group,the positive cell rates of Ki67 and L/M opsin increased in T-MYCN Y1,T-MYCN Y2 and WERI-Rb-1 groups(all P＜0.001).The relative expression levels of MYCN mR-NAs in T-MYCN Y1,T-MYCN Y2 and WERI-Rb-1 groups were significantly higher than those in the control group(all P＜0.001).The relative expression levels of CCNB1 and CDK1 mRNAs also increased significantly in the three groups,com-pared with those in the control group(all P＜0.01).There was no significant difference in the relative expression of SYK mRNAs between T-MYCN Y1 and control groups(P＞0.05).The relative expression level of RXRγ mRNAs was significantly higher in the T-MYCN Y1 group than that in the control group(P＜0.05).The relative expression levels of SYK and RXRγmRNAs in T-MYCN Y2 and WERI-Rb-1 groups were significantly increased,compared with those in the control group(all P＜0.05).GO enrichment analysis showed that these differentially-expressed proteins were enriched into protein complex assembly and mitochondria pathways.KEGG enrichment analysis revealed that the enriched pathways of these differential-ly-expressed proteins included carbon metabolism,metabolic pathway and fatty acid degradation.Both proteomics and Western blot analyses indicated that OTX2 expression levels were the highest in the WERI-Rb-1 group,second highest in the T-MYCN Y2 group,and the lowest in the T-MYCN Y1 group(all P＜0.01).According to qRT-PCR,the expression levels of OTX2 mRNAs in T-MYCN Y1,T-MYCN Y2 and WRI-Rb-1 cells with OTX2 knockdown were lower than those in empty vec-tor controls(all P＜0.05).The growth curve of cells showed that after knocking down OTX2 in the three groups of cells,both cell growth and proliferation ability decreased significantly(all P＜0.001).Conclusion During the development of retinal tumors induced by MYCN overexpression,cells gradually exhibit characteristics similar to WERI-Rb-1 cells,which are a typical RB cell line.OTX2 plays an important role in MYCN amplification or the growth and proliferation of highly ex-pressed RB.Targeting OTX2 may become a new research direction for the treatment of RB.

Objective:To investigate the effect and safety of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating the chronic pancreatitis (CP) patients with main pancreatic duct (MPD) stones and to analyze the influencing factors of success of lithotripsy.Methods:Clinical data of 132 patients with CP complicated with MPD stones treated with P-ESWL in the Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to December 2023 were retrospectively analyzed, including 103 males and 29 females, aged (50.3±16.9) years. The times of P-ESWL, the success rate of stone fragmentation, the necessity of combining endoscopic retrograde cholangiopancreatograhy (ERCP), clearance rate of MPD stones, and incidence of post-P-ESWL complications (acute pancreatitis, abdominal hematoma, infection, steinstrasse, perforation, etc.) were evaluated. The factors influencing the success rate of lithotripsy were analyzed using univariate and multivariate logistic regression.Results:All patients underwent P-ESWL treatment, with (2.23±0.82) times of P-ESWL per person. The success rate of stone fragmentation was 87.1%(115/132). Of 107 CP patients (81.1%, 107/132) were treated with their first P-ESWL. Of 12 patients (9.1%, 12/132) underwent single P-ESWL, and 120 (90.9%, 120/132) underwent P-ESWL combined with ERCP. There were 95 cases (72.0%, 95/132) with effective removal of stones, and 62 (47.0%, 62/132) with complete removal of stones. Post-P-ESWL complications included eight cases (6.1%, 8/132) of acute pancreatitis, two (7.6%, 2/132) of steinstrasse complicated with acute pancreatitis and one (0.8%, 1/132) of abdominal hematoma. No infection or perforation occurred. Multivariate logistic regression analysis showed that the higher CT value of stones ( OR=1.239, 95% CI: 1.040-1.477, P=0.017) was associated with the lower success rate of stone fragmentation. Conclusion:P-ESWL is safe and effective in treating patients with CP complicated with MPD stones. The CT value of stones is a risk factor for the success rate of P-ESWL.

To review the clinical characteristics, short-term outcomes, and risk factors of patients with infective endocarditis(IE) who underwent surgical treatment at a single center, and to summarize treatment experience.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

OBJECTIVE: To investigate the predictive value of oxygenation index (PaO₂/FiO₂) at intensive care unit (ICU) admission on 30-day mortality in patients with sepsis. METHODS: A retrospective study was conducted. Patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to October 2023 were enrolled. The demographic information, comorbidities, sites of infection, vital signs and laboratory test indicators at the time of admission to the ICU, disease severity scores within 24 hours of admission to the ICU, treatment process and prognostic indicators were collected. According to the PaO₂/FiO₂ at ICU admission, patients were divided into Q1 group (PaO₂/FiO₂ of 4.1-16.4 cmHg, 1 cmHg ≈ 1.33 kPa), Q2 group (PaO₂/FiO₂ of 16.5-22.6 cmHg), Q3 group (PaO₂/FiO₂ of 22.7-32.9 cmHg), and Q4 group (PaO₂/FiO₂ of 33.0-94.8 cmHg). Differences in the indicators across the four groups were compared. Multifactorial Cox regression analysis was used to assess the relationship between PaO₂/FiO₂ and 30-day mortality of patients with sepsis. The predictive value of PaO₂/FiO₂, sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) on 30-day prognosis of patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 1 711 patients with sepsis were enrolled, including 428 patients in Q1 group, 424 patients in Q2 group, 425 patients in Q3 group, and 434 patients in Q4 group. 622 patients died at 30-day, the overall 30-day mortality was 36.35%. There were statistically significant differences in age, body mass index (BMI), history of smoking, history of alcohol consumption, admission heart rate, respiratory rate, APACHE II score, SOFA score, Glasgow coma score (GCS), site of infection, Combined chronic obstructive pulmonary disease (COPD), blood lactic acid (Lac), prothrombin time (PT), albumin (Alb), total bilirubin (TBil), pH, proportion of mechanical ventilation, duration of mechanical ventilation, proportion of vasoactive medication used, and maximal concentration, length of ICU stay, hospital stay, incidence of acute kidney injury, in-hospital mortality, 30-day mortality among the four groups. Multivariate Cox regression analysis showed that after adjusting for confounding factors, for every 1 cmHg increase in PaO₂/FiO₂ at ICU admission, the 30-day mortality risk decreased by 2% [hazard ratio (HR) = 0.98, 95% confidence interval (95%CI) was 0.98-0.99, P < 0.001]. The 30-day mortality risk in the Q4 group was reduced compared with the Q1 group by 41% (HR = 0.59, 95%CI was 0.46-0.76, P < 0.001). The fitted curve showed that a curvilinear relationship between PaO₂/FiO₂ and 30-day mortality after adjustment for confounders. In the inflection point analysis, for every 1 cmHg increase in PaO₂/FiO₂ at PaO₂/FiO₂ < 28.55 cmHg, the risk of 30-day death in sepsis patients was reduced by 5% (HR = 0.95, 95%CI was 0.94-0.97, P < 0.001); when PaO₂/FiO₂ ≥ 28.55 cmHg, there was no statistically significant association between PaO2/FiO2 and the increase in the risk of 30-day death in sepsis (HR = 1.01, 95%CI was 0.99-1.02, P = 0.512). ROC curve analysis showed that the area under the curve (AUC) for the prediction of 30-day mortality by admission PaO₂/FiO₂ in ICU sepsis patients was 0.650, which was lower than the predictive ability of the SOFA score (AUC = 0.698) and APACHE II score (AUC = 0.723). CONCLUSION In patients with sepsis, PaO₂/FiO₂ at ICU admission is strongly associated with 30-day mortality risk, alerting healthcare professionals to pay attention to patients with low PaO₂/FiO₂ for timely interventions.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Retrospective Studies ; Prognosis ; Hospital Mortality ; Oxygen ; Male ; Predictive Value of Tests ; Female ; Middle Aged ; Aged

Objective To observe the efficacy of different pulse dose of ropivacaine combined with sufentanil for programmed intermittent epidural bolus(PIEB)infusion in labor analgesia and its impact on maternal and neonatal safety.Methods A total of 300 parturients undergoing labor anal-gesia were randomly divided into group A,group B,and group C,with 100 parturients in each group.The analgesic regimen consisted of 0.08％ropivacaine combined with 0.5 μg/mL sufentanil.The bolus infusion doses for groups A,B,and C were 6 mL,8 mL,and 10 mL,respectively,with a bolus interval of 40 min.The patient-controlled analgesia(PCA)dose was the same as the corre-sponding bolus dose,with a lockout time of 15 min.The medication was discontinued after fetal deliv-ery,with a limit dose of 30 mL/h.The Visual Analogue Scale(VAS)scores before analgesia(T0)and at 30 min(T1),1 h(T2),2 h(T3),3 h(T4)after analgesia,full dilation of the cervix(T5),and immediately after delivery(T6)were compared among groups.Additionally,the inci-dence of breakthrough pain,the first occurrence time of breakthrough pain,the rate of rescue analge-sia,the number of PCA pump presses,delivery outcomes,and neonatal conditions were compared.Results At each time points from T1 to T6,the VAS scores in all three groups were lower than that at T0,and were lower in groups B and C than those in group A(P＜0.05).However,there was no statistically significant difference in VAS scores between groups B and C(P＞0.05).The incidence of breakthrough pain,the rate of rescue analgesia,and the number of PC A pump presses were lower in the groups B and C than those in the group A,and the first occurrence time of breakthrough pain was later in groups B and C than those in group A(P＜0.05).There were no statistically signifi-cant differences among the three groups in neonatal birth weight,1-min and 5-min Apgar scores,neonatal behavioral neurological assessment(NBNA)scores,and the incidence of neonatal asphyxia(P＞0.05).Conclusion 0.08％ropivacaine combined with 0.5 μg/mL sufentanil for PIEB in labor analgesia is safe and effective,with a bolus dose of 8 mL achieving good analgesic effects and having minimal impact on both mothers and neonates.

Objective:To observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. Methods:A family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks.Results:Among the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from -8.00 to-18.00 D. BCVA ranged from no light perception to 0.6 -. There were 2 cases each of vitreous membrane-like and "bead-like" opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains Conclusion:The COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.