To explore the effect of Macleaya cordata extract(MCE)on growth performance and serum biochemistry of Sichuan White Geese,and to analyze its mechanism of action by network pharmacology and molecular docking technology combined with animal experiments verification.A total of 90 1-day-old healthy goslings were randomly divided into 5 groups with 18 goslings per group after 5 d of adaptive feeding.The control group(CON)was fed with basal diet,the antibiotic group(CTC)was supplemented with 450 mg/kg chlortetracycline premix,and the low MCE group(MCEL),medium MCE group(MCEM)and high MCE group(MCEH)were supple-mented with 200,300 and 400 mg/kg MCE,respectively.The experimental period was 21 d.On the basis of the above experiments,Network pharmacology and molecular docking technology were used to predict the core targets and signaling pathways of MCE to promote geese growth from the levels of antioxidant,immune and apoptosis,and the expression levels of the core target genes were detected by Real-time fluorescence quantitative PCR.The results showed that compared with the CON group,MCE supplementation could increase the average daily weight gain,decrease the ratio of feed to gain,significantly increase the contents of serum GH,T3,T4,TP and ALB(P＜0.05),and significantly decrease the contents of serum AST and TG(P＜0.05).Network pharmacology analysis predicted 2 active ingredient and 237 active ingredient targets,and concluded that the mechanism of MCE promoting the growth of Sichuan White Geese may be related to the role of 5 key targets such as SRC,HSP90AA1,CASP3,ESR1 and MAPK14,and the action of MAPK,apop-tosis and other signaling pathways.Molecular docking results showed that the active ingredients of sanguinarine and chelerythrine in MCE could act through MAPK14.The validation results of core targets showed that MCE could significantly reduce the mRNA expression levels of CytC,CASP2,CASP3 and CASP9 in spleen(P＜0.05)and significantly increase the mRNA expression levels of Mcl-1(P＜0.05).These results indicated that MCE could promote the growth performance of Si-chuan White Geese by regulating apoptosis,promoting the secretion of serum growth-related hor-mones and improving biochemical indicators.

Objective To explore a Bayesian logistic regression model for step－in dosing regimens(eBLRM),which considers the cumulative toxicity probability across different dosing cycles to identify the maximum tolerated schedule(MTS).Methods The Bayesian logistic regression model(BLRM)was extended to obtain a posterior estimate for the cumulative toxicity probability of the last cycle based on accumulated patient data,enabling exploration of dose sequences.Results The performance of eBLRM was evaluated by comparison with the existing methods.Simulation results indicated that eBLRM performed better or equivalent in the proportion of the correct selection of MTS and patients assigned to real MTS under low－toxicity scenarios.In the case of high－toxicity scenarios,eBLRM had a higher proportion of early trial termination due to safety,resulting in slightly inferior performance compared to the existing method.Conclusion The eBLRM method demonstrates relatively good performance,providing a simple and comprehensible dose exploration approach for step－in dosing regimens.

Objective To quantify the intraretinal fluid(IRF)volume in patients with diabetic macular edema(DME)using a deep learning-based three-dimensional segmentation model and to investigate the relationship of IRF volume with visual function and retinal biomarkers based on optical coherence tomography(OCT).Methods A total of 37 pa-tients(42 eyes)with DME who received treatment in the Ophthalmology Department of Sichuan Provincial People's Hospi-tal from July 2022 to September 2024 were prospectively included in this study.A three-dimensional segmentation model was used to automatically quantify the IRF volume within a 6 mm × 6 mm OCT scan at baseline and at the last follow-up.The correlation of visual acuity with IRF volume,central subfield thickness(CST),disorganization of the retinal inner lay-ers(DRIL),hyperreflective foci(HRF),external limiting membrane(ELM),ellipsoid zone(EZ),and vitreomacular in-terface abnormality(VMIA)was analyzed at baseline and the last follow-up.Additionally,the correlation of IRF volume with CST,DRIL,HRF,ELM,EZ,and VMIA was analyzed at both time points.Furthermore,the correlation of the visual acuity at the last follow-up with the IRF volume,CST,DRIL,HRF,ELM,EZ,and VMIA at baseline was analyzed.Results Compared with the baseline value,patients exhibited a significant increase in the best corrected visual acuity(BCVA)(logMAR),a significant decrease in the IRF volume and CST,a significant reduction in the HRF,a significant re-covery in the DRIL,ELM,and EZ(all P＜0.05),and no significant changes in the VMIA(P=1.000)at the last follow-up.At baseline,the BCVA was negatively correlated with the IRF volume,CST,DRIL,and HRF,but positively correlated with the ELM and EZ(all P＜0.05);there was no correlation between the BCVA and VMIA(P=0.069).At the last follow-up,the BCVA was negatively correlated with the DRIL,HRF,and VMIA,but positively correlated with the ELM and EZ(all P＜0.01);the BCVA did not correlate with the IRF volume and CST(P=0.419 and 0.994).At baseline,the IRF volume was positively correlated with the CST(P＜0.001)but negatively correlated with the ELM and EZ(P＜0.01);the IRF vol-ume did not correlate with the DRIL,HRF,and VMIA(all P＞0.05).At the last follow-up,the IRF volume was positively correlated with the CST and HRF(all P＜0.01);however,it was not correlated with the DRIL,ELM,EZ,and VMIA(all P＞0.05).The BCVA at the last follow-up was positively correlated with the BCVA,ELM,and EZ at baseline,but negative-ly correlated with the IRF volume,CST,DRIL,HRF,and VMIA at baseline(all P＜0.05).Conclusion The baseline IRF volume in DME patients is an important influencing factor of visual acuity at baseline and the last follow-up.Hence,the IRF volume may serve as a potential biomarker in the management of DME.

Objective:To establish and assess the quality control and improvement system for metabolic and bariatric surgery in Beijing.Methods:Based on relevant documents from the National Health Commission and the Beijing Municipal Health Commission,and referencing the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) by the American Society for Metabolic and Bariatric Surgery,a quality control system was developed under the Beijing Quality Control and Improvement Center of Metabolic and Bariatric Surgery. The system incorporated on-site evaluations,data registration,and specialized training. From May to December 2023,on-site assessments were conducted at 21 hospitals in Beijing performing bariatric surgery,evaluating personnel qualifications,infrastructure,clinical workflows,and postoperative follow-up. A quality control database was created to collect real-time surgical data,and training was provided for data entry and professional skills. Assessment results were classified as excellent,qualified,or needing improvement,with rectification suggestions offered and follow-up visits conducted to track progress.Results:All 21 hospitals achieved a 100% compliance rate for surgical indications, 16 (76.2%) met standardized surgical operation criteria,and 14 (66.7%) had standardized postoperative management. However,only 5 (23.8%) achieved a 12-month postoperative follow-up rate of ≥60%,and 4 (19.1%) had established specialized databases. Key challenges included insufficient specialized staffing (19.1%), lack of multidisciplinary collaboration (47.6%), inadequate equipment (57.1%), and low follow-up rates (57.1%). The database collected data from over 2 000 patients across 111 fields. After rectification, specialized database coverage rose to 61.9% (13 hospitals). Multi-level training programs developed backbone physicians and specialized nurses,significantly addressing the shortage of specialized personnel.Conclusion:The quality control system established in this study,through the integration of on-site evaluation,data registration,and specialized training,effectively enhances the standardization of surgical practices and data management capabilities.

To explore the effect of Macleaya cordata extract(MCE)on growth performance and serum biochemistry of Sichuan White Geese,and to analyze its mechanism of action by network pharmacology and molecular docking technology combined with animal experiments verification.A total of 90 1-day-old healthy goslings were randomly divided into 5 groups with 18 goslings per group after 5 d of adaptive feeding.The control group(CON)was fed with basal diet,the antibiotic group(CTC)was supplemented with 450 mg/kg chlortetracycline premix,and the low MCE group(MCEL),medium MCE group(MCEM)and high MCE group(MCEH)were supple-mented with 200,300 and 400 mg/kg MCE,respectively.The experimental period was 21 d.On the basis of the above experiments,Network pharmacology and molecular docking technology were used to predict the core targets and signaling pathways of MCE to promote geese growth from the levels of antioxidant,immune and apoptosis,and the expression levels of the core target genes were detected by Real-time fluorescence quantitative PCR.The results showed that compared with the CON group,MCE supplementation could increase the average daily weight gain,decrease the ratio of feed to gain,significantly increase the contents of serum GH,T3,T4,TP and ALB(P＜0.05),and significantly decrease the contents of serum AST and TG(P＜0.05).Network pharmacology analysis predicted 2 active ingredient and 237 active ingredient targets,and concluded that the mechanism of MCE promoting the growth of Sichuan White Geese may be related to the role of 5 key targets such as SRC,HSP90AA1,CASP3,ESR1 and MAPK14,and the action of MAPK,apop-tosis and other signaling pathways.Molecular docking results showed that the active ingredients of sanguinarine and chelerythrine in MCE could act through MAPK14.The validation results of core targets showed that MCE could significantly reduce the mRNA expression levels of CytC,CASP2,CASP3 and CASP9 in spleen(P＜0.05)and significantly increase the mRNA expression levels of Mcl-1(P＜0.05).These results indicated that MCE could promote the growth performance of Si-chuan White Geese by regulating apoptosis,promoting the secretion of serum growth-related hor-mones and improving biochemical indicators.

Objective:To systematically review recent domestic and international literature on the use of extracorporeal membrane oxygenation (ECMO) in obstetric critical care and provide evidence-based support for clinical decision-making.Methods:Literature published between January 1, 2014, and December 31, 2024, in both Chinese and English was retrieved from databases including CNKI, Wanfang Medical Network, Chinese Medical Journal Network, PubMed, and Embase. Data on maternal age, gestational age, diagnosis, ECMO type, ECMO duration, pregnancy outcomes, and maternal and neonatal survival rates were extracted from relevant studies.Results:Among 1 306 retrieved articles, 214 met the inclusion criteria, involving a total of 355 obstetric patients who received ECMO treatment. The majority of patients (58.9%, 209/355) were treated postpartum. The most common indications for ECMO initiation included pulmonary infection (32.7%, 116/355), pulmonary embolism (24.5%, 87/355), pulmonary hypertension (12.4%, 44/355), sepsis (9.6%, 34/355), and peripartum cardiomyopathy (6.2%, 22/355). The modes of ECMO used in the obstetric population were venovenous (VV) in 49.6%(176/355) and venoarterial (VA) in 44.2%(157/355) of cases. The overall maternal survival rate was 82.0%(291/355), while the fetal/neonatal survival rate was 74.4%(264/355). Bleeding was the most common complication (35.5%, 126/355), followed by thrombosis (14.6%, 52/355) and infections related to ventilator or cannulation sites (19.2%, 68/355).Conclusions:ECMO can serve as an effective temporary organ support therapy for critically ill patients during pregnancy and the postpartum period.

Di-(2-ethylhexyl)phthalate(DEHP)is an environmental pollutant commonly found in plastic products and has toxic effects on female reproductive system.DEHP can interfere with the synthesis of progesterone,testosterone and estradiol through female hypothalamic-pituitary-ovarian axis,aggravate insulin resistance and obesity by affecting glucose and lipid metabolism,and cause ovarian damage through inducing oxidative stress,excessive autophagy and pyroptosis of oocyte or granulosa cells.It can also alter epigenetic genes relating to follicular development and prevent follicles from mature.These factors are closely contribute to the pathogenesis of polycystic ovary syndrome.We systematically summarizes the mechanism of DEHP interfering with ovarian function and inducing polycystic ovary syndrome,in order to provide help for the prevention and treatment of female reproductive injury from environmental pollutant.

This study investigated the specific immune response of BALB/c mice that was induced by a circular RNA (circRNA) vaccine expressing the herpes simplex virus type II (HSV-2) glycoprotein D (gD). The aim was to evaluate the immunological potential of this vaccine and lay a foundation for developing an mRNA vaccine against HSV-2. PCR and homologous recombination were employed to integrate the gD gene obtained from the pT7AMP-gD ectodomain plasmid into pUC57 to generate the recombinant plasmid pUC57-circ-gD, which was then sequenced and characterized. In vitro transcription and cyclization were performed on the template DNA to generate pUC57-circ-gD mRNA. To validate the formation of circular RNA, we cleaved the pUC57-circ-gD mRNA with RNase R and employed RT-PCR to validate the cyclization. The pUC57-circ-gD mRNA was then transfected into 293T cells. After 72 h, the cell supernatant was collected, and Western blotting was employed to measure the protein level of gD. Subsequently, the mRNA was encapsulated in lipid nanoparticles (LNPs) by microfluidic encapsulation. BALB/c mice were administrated with the encapsulated mRNA, and blood was collected from the fundus venous plexus after 21 and 35 days, and from the enucleated eyeballs after 49 days. Enzyme-linked immunosorbent assay was employed to measure the titers of antibodies, including virus-neutralizing antibodies. After 49 days, spleens were harvested and assessed for secretion of interferon-gamma (IFN-γ) by solid-phase enzyme-linked immunospot. The results showed successful construction and sequencing of the recombinant plasmid. RNase R digestion confirmed the presence of circular RNAs. Western blotting of the 293T cells transfected with the mRNA showed clear specific bands. The quality of the vaccine was tested by size exclusion chromatography-high performance liquid chromatography, which showed that the purity of the vaccine was about 90%. The mRNA-LNP showcased the particle size of 82.76 nm and an encapsulation rate of approximately 98%. Following three-dose vaccination, all immunized mice exhibited steady weight gain with 100% survival rate throughout the 28-day observation period, indicating no significant acute toxicity associated with the vaccine formulation. The immunized mice showed dose-dependent increases in serum IgG antibody titer and IFN-γ secretion by splenocytes and they were resistant to virus attacks. These findings indicate good immunogenicity and persistence of the pUC57-circ-gD mRNA vaccine, providing a reference for further studies on circRNA vaccines.
Animals ; Mice, Inbred BALB C ; RNA, Circular ; Mice ; Humans ; Herpesvirus 2, Human/genetics* ; Viral Envelope Proteins/genetics* ; Antibodies, Viral/blood* ; HEK293 Cells ; Female ; Nanoparticles ; Plasmids

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal