AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Cardiotocography (CTG) is a non-invasive and important tool for diagnosing fetal distress during pregnancy. To meet the needs of intelligent fetal heart monitoring based on deep learning, this paper proposes a TWD-MOAL deep active learning algorithm based on the three-way decision (TWD) theory and multi-objective optimization Active Learning (MOAL). During the training process of a convolutional neural network (CNN) classification model, the algorithm incorporates the TWD theory to select high-confidence samples as pseudo-labeled samples in a fine-grained batch processing mode, meanwhile low-confidence samples annotated by obstetrics experts were also considered. The TWD-MOAL algorithm proposed in this paper was validated on a dataset of 16 355 prenatal CTG records collected by our group. Experimental results showed that the algorithm proposed in this paper achieved an accuracy of 80.63% using only 40% of the labeled samples, and in terms of various indicators, it performed better than the existing active learning algorithms under other frameworks. The study has shown that the intelligent fetal heart monitoring model based on TWD-MOAL proposed in this paper is reasonable and feasible. The algorithm significantly reduces the time and cost of labeling by obstetric experts and effectively solves the problem of data imbalance in CTG signal data in clinic, which is of great significance for assisting obstetrician in interpretations CTG signals and realizing intelligence fetal monitoring.
Humans ; Pregnancy ; Female ; Cardiotocography/methods* ; Deep Learning ; Neural Networks, Computer ; Algorithms ; Fetal Monitoring/methods* ; Heart Rate, Fetal ; Fetal Distress/diagnosis* ; Fetal Heart/physiology*

Objective To develop a 3D visualization endoscopic navigation system based on CT portal angiography (CTPA) and explore its clinical value in assisting precise treatment of esophageal and gastric varices (EGV). Methods Patients with EGV needing treatment in the Department of Gastroenterology of Zhongshan Hospital, Fudan University from September 2021 to April 2023 were collected. Preoperative examinations including CTPA and hematological examinations were performed, and a 3D visualization endoscopic navigation system was developed to assist endoscopic treatment. Real time comparison was made between the endoscopic 3D portal vein system image reconstructed by intelligent imaging and the actual endoscopic observation of the vascular morphology inside the cavity. The responsible blood vessels that are prone to bleeding were embolized using a sandwich injection method of “lauromacrogol+tissue adhesive+lauromacrogol”. For patients with portal shunting, ultrasound-guided coil insertion was performed. Postoperative endoscopic ultrasound or CTPA was used reexamination to evaluate vascular embolism and complications. Results A total of 13 patients successfully underwent endoscopic ultrasound-guided variceal embolization. The average maximum inner diameter of target veins was (3.3\begin{document}$ \pm $\end{document}1.3) cm; on average, implanted coil number was 1(0,2) in each patient, with median dosages of lauromacrogol and tissue adhesive were 9.5(7.8,10.0) mL and 1.5(1.0,2.1) mL respectively. Postoperatively, endoscopic ultrasound detecting confirmed complete occlusion of all target veins. At 8 weeks after treatment, none of the patients experienced rebleeding. At 24 weeks after treatment, rebleeding occurred in 3 patients, on postoperative days 107, 126 and 147, respectively. Conclusion The 3D visualization endoscopic navigation system based on CTPA can effectively and safely assist preoperative diagnosis and intraoperative localization of target blood vessels, which is beneficial for the precise treatment of EGV patients.

OBJECTIVE To establish an UHPLC-MS method for simultaneous determination of 9 bile acids components in Shedan Chuanbei liquid. To analyze the differences of bile acids components from different manufacturers and different batches of product. METHODS Thermo Fisher Scientfic Bremen HYPERSIL GOLD(2.1 mm×100 mm, 1.9 µm) was selected as the chromatographic column. The mobile phase was 0.1% formic acid-water and methanol with gradient elution at a flow rate of 0.2 mL·min−1, and the column temperature was 40 ℃. HESI negative ion mode was used for mass spectrometry, and PRM scanning mode was used for mass spectrometry data. RESULTS The calibration curves of 9 biles acids were linear in their own range(r≥0.999 2). The average recoveries ranged from (95.5±1.52)% to (103.1±3.81)%. The RSD ranged from 1.1% to 5.5%. Nine bile acids components including taurocholic acid, tauroursodesoxycholic acid, 7-ketone-3α,12-α-hydroxyl cholanic acid, taurochenodeoxy-cholic acid, sodium taurodeoxycholate, cholic acid, sodium taurocholate, chenodeoxycholic acid and deoxycholic acid were tentatively identified from 19 batches of test samples. Taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate sodium were detected in all the test batches. CONCLUSION This method is simple and stable, and has certain reference value for improving the quality control and evaluation of Shedan Chuanbei liquid.

Objective:To explore the clinical effect of perforator pedicled propeller flap (PPPF) in reconstruction of soft tissue defect in ankle and foot, as well as the role of preoperative ultrasonography in assistance of the location of perforators in donor site.Methods:From January 2017 to June 2023, the Department of Microorthopedics of the Second Affiliated Hospital of Luohe Medical College of Higher Education applied PPPF to reconstruct small and medium-sized soft tissue defects in the ankle and foot for 26 patients. The patients were 17 males, 9 females, aged 18 to 68 years old with 46 years old in average. The defect sites were 3 in forefoot and 6 in midfoot and combined with different degrees of tendon and bone exposure, 17 in ankle and heel and combined with various degrees of bone exposure, 12 with ankle open injury and 5 with Achilles tendon exposure. The area of soft tissue defects ranged from 2.5 cm×1.5 cm to 16.0 cm × 6.5 cm. The width of injury was measured before surgery, and a HHD was used to detect the perforators proximal to the defect site, and then high-frequency CDU was used to locate and confirm the location of the perforator and its alignment, blood flow and diameter. The line drawn between the 2 perforators was set as the axis of flap. The donor site was assessed by a "pinching and lifting" method to determine a direct closure of donor site or to have it closed by a flap transfer. The sizes of flap were from 2.8 cm×1.5 cm to 24.0 cm×7.5 cm. Twenty-two donor sites were directly closed and 4 received flap transfers. Four flaps had sutures with the skin nerves in the recipient site. Masquelet technique was performed in 6 patients with bone defects in the surgery. Patients received outpatient reviews with 1-2 weeks of intervals in the first 2 months after surgery, and X-ray reviews per 1-2 months for those with bone implants until bone healing.Results:All flaps survived successfully without any special treatment after surgery, except 1 flap that had blood vessel congestion and showed swelling and poor blood supply to the distal flap at 24 hours after surgery. The blood vessel congestion was revised by removal of part of the suture at the tip of flap pedicle. One week later, the tip of the flap remained with a small area of necrosis, which was then healed after dressing changes. A total of 21 patients were included in postoperative follow-up with 4 months to 3 years. All of the flaps had satisfactory appearance, colour and texture, and without any ulceration. Three cases of nerve suture were also included in follow-up. According to the assessment criteria of British Medical Research Council (BMRC), the sensory recovery of the flaps was found of S 2 in 1 flap and S 3 in 2 flaps. According to the American Orthopaedic Foot and Ankle Society (AOFAS), the ankle-hindfoot function scores, there were excellent in 16 patient and good in 5 patients. Conclusion:With the assistance of ultrasound, the PPPF can be effectively used in reconstruction of soft tissue defects in ankle and foot.

Objective To explore the lipid-lowering effect of Qige Decoction before and after compatibility through the combination of pharmacodynamics and liver metabolomics,and to provide new research strategies for exploring the scientific notation of traditional Chinese medicine compatibility.Methods According to the pharmacodynamic strategy,three groups of drug administration were set up as Qige Decoction group,Astragali Radix-Puerariae Radix group,and Pericarpium Citri Tangerinae group.Four indices of blood lipids,serum biochemical indicators,and liver morphology and pathology were used to evaluate the intervention effect of Qige Decoction on hyperlipidemic rats.Liver metabolomics technology was used to analyze the effects of Qige Decoction on metabolites before and after compatibility,and multivariate statistical analysis was used to evaluate the differences between groups in terms of differential metabolites and metabolic pathways.Results Compared with the model group,the callback abilities of four indices of blood lipid in the Qige Decoction group were higher than those in Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group,among which the total cholesterol(TC)and triglyceride(TG)levels in the Qige Decoction group decreased(P＜0.05).A total of 86 potential biomarkers were identified by liver metabolomics,with 23,13,and 7 metabolites being significantly different in the Qige Decoction group,Astragali Radix-Puerariae Radix group,and Pericarpium Citri Tangerinae group,respectively(P＜0.05).Metabolic pathway analysis of 29 specific biomarkers with significant callback effects showed that they were related to glycerophospholipid metabolism,linoleic acid metabolism,α-linolenic acid metabolism,sphingolipid metabolism,arachidonic acid metabolism,and unsaturated fatty acid biosynthesis.Qige Decoction mainly regulates glycerophospholipid and linoleic acid metabolism,and uniquely acts on sphingolipid metabolism.Conclusion Qige Decoction has more lipid-lowering targets after compatibility,with better lipid-lowering effects than the Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group.This study provides experimental evidence and research strategies for further revealing the scientific notation of traditional Chinese medicine compatibility.

Objective To investigate the impact of variations in RNA-binding motif protein 20(RBM20)and muscle-restricted coiled-coil(MURC)digenic heterozygosity variation on the structural and biological characteristics of human cardiomyocyte AC 16(an adult left ventricular myocardial cell line).Methods Cardiomyocyte AC 16 cell lines were constructed with control,negative scramble,wild-type,MURC single-gene mutant,RBM20 single-gene mutant,and RBM20 and MURC digenic mutant groups.The localization of RBM20 and MURC in cardiomyocytes,cell area,cytoskeletal arrangement,cytoskeleton-related proteins,cell polarity,and intracellular calcium concentration were observed using Western blotting,immunofluorescence staining,and reverse transcription polymerase chain reaction.Myocardial apoptosis was detected using flow cytometry.Ki-67 staining and wound healing assays were performed to detect cardiomyo-cyte proliferation and migration,respectively.Results Digenic mutations had a more pronounced impact than single-gene mutations in RBM20 or MURC on the structural and biological characteristics of cardiomyocytes,manifested by increased cell area,upregulated mRNA expression of hypertrophy-related genes,such as myosin heavy chain 7 and alpha-actin,increased cytoskeleton disturbance,decreased flu-orescence intensity of cytoskeletal proteins β-tubulin and Vinculin(all P＜0.01);increased fluorescence intensity of the polarity protein Part 6(P＜0.05);and significantly elevated cardiomyocyte apoptosis rate,decreased proliferative activity,and elevated migration rate and intracellular calcium ion concentration(all P＜0.01).Conclusion The digenic heterozygous variation in RBM20 and MURC may induce changes in the morphological structure and biological characteristics of myocardial cells,including increased cell area,cytoskeleton dis-turbance,cell polarity,increased apoptosis rate and mobility,decreased cell proliferation activity,and calcium processing ability.

To improve the effectiveness of bedside localization of nasointestinal tube(NIT)and facilitate the placement of nasointestinal tube into jejunum,we established a procedure and composed a teaching verse for bedside placement of nasointestinal tube based on relevant classical literature and our own practices.Verse content:enteral nutrition means a successful strategy to improve the outcome in critically ill patient management,never hesitate to place nasointestinal tubes when necessary.There are several methods to deal with it,but popularizing it remains a long way off.Half-sitting and swallowing into the esophagus,freely withdrawing signifies the stomach cavity.Passing through the pylorus using light tension on the tube in the right lateral decubitus position.Arriving at the jejunum with low resistance in the left lateral decubitus position.What are the signs of intragastric coiling?Tube return out of nose is the initial observation,Failure of air insufflation indicates tube coiling.Dyeing location surpasses imaging.Vacuum test is the most sensitive,Sequential change from acid to base is specific.Methylene blue test is dramatical for localization.Combining three methods is enough to navigate.Abdominal plain film is the goldan standard and can still be used in ultrasonic era.3-D image establishes overall view.CT reveals the tube route exactly.The teaching verse has become a powerful tool for clinical teaching of manual nasointestinal tube placement in a concise and easy-to-remember form.