The intestine is a complex symbiotic system, and the gut microbiota is closely related to host health. Studies have indicated that the gut microbiota influences physiological functions of the host by producing a variety of metabolites, which act as signaling molecules and substrates for metabolic reactions in the host. Dysbiosis of the gut microbiota affects the abundance of gut microbiota-derived metabolites, thereby influencing host health by disrupting signal transduction in multiple organs. Additionally, dietary compounds can shape the gut microbiota, affecting gut microbiota-derived metabolite levels and regulating host metabolism. This article introduces the methods for mining gut microbiota-derived metabolites, reviews the roles of these metabolites in metabolic diseases and related dietary interventions. Which provides a perspective on the prevention and treatment of metabolic diseases by targeting these metabolites, enriching the knowledge on the role of gut microbiota in the regulation of host metabolism.
Gastrointestinal Microbiome/physiology* ; Humans ; Dysbiosis/microbiology* ; Metabolic Diseases/metabolism* ; Diet

Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.

Objective:To explore the effectiveness and safety of endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD).Methods:A retrospective analysis was conducted on data of 16 patients who underwent EUS-PD because of endoscopic retrograde pancreatography (ERP) failure, poor effectiveness or anatomical changes and couldn't undergo the routine ERP in Nanjing Drum Tower Hospital from June 2018 to July 2022. The technical success of EUS-PD, clinical efficacy and post-procedure adverse events were analyzed.Results:In the 16 patients, there were 14 males and 2 females, with age of 50.69±12.95 years. A total of 19 times of EUS-PD operations were included, 3 of them were rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), 15 transgastric or transenteric EUS-guided stent placement and 1 was EUS-guided nasopancreatic duct placement. Technical success was achieved in 84.21% (16/19) patients, and among whom 93.75% (15/16) achieved clinical success. The overall incidence of postoperative adverse events was 52.63% (10/19) including 47.37% (9/19) abdominal pain, 15.79% (3/19) fever and 15.79% (3/19) postoperative pancreatitis. All adverse effects were relieved after general conservative treatment and no primary disease or surgery-related death occurred. The mean follow-up was 17.6 (8.2,22.3) months and 93.75% (15/16) of the patients were followed up. By the time of follow-up, 76.92% (10/13) of the patients who had successfully received EUS-PD had no recurrence of abdominal pain or distension.Conclusion:EUS-PD is a safe and effective alternative therapy for those with pancreatic diseases with ERP failure, poor efficacy or anatomical changes.

The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.

Objective : To explore a non⁃invasive assay for screening osteosarcoma patients with positive programed death receptor⁃1 ( PD⁃1) /programmed death receptor ligand⁃1 ( PD⁃L1) signaling pathway expression Methods : The subcutaneous tumor bearing mouse model of human Osteosarcoma cells ( OS⁃732) was established by the method of tumor formation , and toxicity test was performed to verify the toxicity of PD⁃L1 antibody to mouse organs . 124 I ⁃anti⁃PD⁃L1 monoclonal antibody molecular probe was further synthesized , and OS⁃732 rats were injected with 18 . 5 MBq 124 I ⁃anti⁃PD⁃L1 probe in tail vein to start OS⁃732 osteosarcoma Micro Positron E mission Tomography/ Computed Tomography (Micro⁃PET/CT) imaging. Results : OS⁃732 osteosarcoma model was successfully constructed , immunohistochemistry confirmed the presence of PD⁃L1 expression in OS⁃732 osteosarcoma , and Micro⁃PET/CT imaging was successfully performed at different time points (2 , 24 and 48 h after probe injection) to achieve non⁃invasive real⁃time observation of PD⁃L1 in OS⁃732 osteosarcoma . Conclusion In this study , the 124 I ⁃anti⁃PD⁃L1 monoclonal antibody molecular probe was constructed in vitro , and Micro PET /CT imaging verified that the probe successfully targeted the PD⁃L1 receptor of OS⁃732 Osteosarcoma , and showed clear immune imaging , indicating that it is hopeful to achieve non⁃invasive screening of Osteosarcoma patients with PD⁃L1 positive expression in clinical practice , and this technology might benefit the majority of Osteosarcoma patients .

Objective:To evaluate the role of G-protein coupled receptor 37 (GPR37) in cognitive dysfunction in a mouse model of neuropathic pain.Methods:SPF-grade healthy male C57BL/6 mice and GPR37 knockout (GPR37-KO) mice, aged 3 months, with a body weight of approximately 20 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (Con group), neuropathic pain group (NPP group), GPR37-KO+ control group (GPR37-KO Con group) and GPR37-KO+ neuropathic pain group (GPR37-KO NPP group). The mouse model of neuropathic pain was established by ligation of the sciatic nerve. The thermal paw withdrawal latency (TWL) and mechanical paw withdrawal threshold (MWT) were measured at 7 days after surgery. The open field test and Morris water maze test were performed at 28 days after surgery. The mice were subsequently sacrificed, and the medial prefrontal cortex (mPFC) was obtained for determination of the level of phosphorylated calcium/calmodulin-dependent protein kinase Ⅱ(p-CAMKⅡ) and expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95). Results:Compared to Con group, no significant changes were found in the parameters in GPR37-KO Con group ( P>0.05), and TWL was significantly shortened, MWT was decreased, the time the animal spent in central area was prolonged and the platform-crossing times were increased in the open field test, and the escape latency was prolonged and platform-crossing times were decreased in the Morris water maze test, and the expression of p-CAMKⅡ, BDNF and PSD-95 in the mPFC was down-regulated in NPP group ( P<0.05). Compared with NPP group, TWL was significantly shortened, MWT was decreased, the time the animal spent in central area was prolonged and the platform-crossing times were increased in the open field test, and the escape latency was prolonged and platform-crossing times were decreased in the Morris water maze test, and the expression of p-CAMKⅡ, BDNF and PSD-95 in the mPFC was down-regulated in GPR37-KO NPP group ( P<0.05). Conclusions:GPR37 is involved in the development of cognitive dysfunction in mice with neuropathic pain, and the mechanism may be related to its modulation of synaptic plasticity.

Nitrate is the main form of inorganic nitrogen that crop absorbs, and nitrate transporter 2 (NRT2) is a high affinity transporter using nitrate as a specific substrate. When the available nitrate is limited, the high affinity transport systems are activated and play an important role in the process of nitrate absorption and transport. Most NRT2 cannot transport nitrates alone and require the assistance of a helper protein belonging to nitrate assimilation related family (NAR2) to complete the absorption or transport of nitrates. Crop nitrogen utilization efficiency is affected by environmental conditions, and there are differences between varieties, so it is of great significance to develop varieties with high nitrogen utilization efficiency. Sorghum bicolor has high stress tolerance and is more efficient in soil nitrogen uptake and utilization. The S. bicolor genome database was scanned to systematically analyze the gene structure, chromosomal localization, physicochemical properties, secondary structure and transmembrane domain, signal peptide and subcellular localization, promoter region cis-acting elements, phylogenetic evolution, single nucleotide polymorphism (SNP) recognition and annotation, and selection pressure of the gene family members. Through bioinformatics analysis, 5 NRT2 gene members (designated as SbNRT2-1a, SbNRT2-1b, SbNRT2-2, SbNRT2-3, and SbNRT2-4) and 2 NAR2 gene members (designated as SbNRT3-1 and SbNRT3-2) were identified, the number of which was less than that of foxtail millet. SbNRT2/3 were distributed on 3 chromosomes, and could be divided into four subfamilies. The genetic structure of the same subfamilies was highly similar. The average value of SbNRT2/3 hydrophilicity was positive, indicating that they were all hydrophobic proteins, whereas α-helix and random coil accounted for more than 70% of the total secondary structure. Subcellular localization occurred on plasma membrane, where SbNRT2 proteins did not contain signal peptides, but SbNRT3 proteins contained signal peptides. Further analysis revealed that the number of transmembrane domains of the SbNRT2s family members was greater than 10, while that of the SbNRT3s were 2. There was a close collinearity between NRT2/3s of S. bicolor and Zea mays. Protein domains analysis showed the presence of MFS_1 and NAR2 protein domains, which supported executing high affinity nitrate transport. Phylogenetic tree analysis showed that SbNRT2/3 were more closely related to those of Z. mays and Setaria italic. Analysis of gene promoter cis-acting elements indicated that the promoter region of SbNRT2/3 had several plant hormones and stress response elements, which might respond to growth and environmental cues. Gene expression heat map showed that SbNRT2-3 and SbNRT3-1 were induced by nitrate in the root and stem, respectively, and SbNRT2-4 and SbNRT2-3 were induced by low nitrogen in the root and stem. Non-synonymous SNP variants were found in SbNRT2-4 and SbNRT2-1a. Selection pressure analysis showed that the SbNRT2/3 were subject to purification and selection during evolution. The expression of SbNRT2/3 gene and the effect of aphid infection were consistent with the expression analysis results of genes in different tissues, and SbNRT2-1b and SbNRT3-1 were significantly expressed in the roots of aphid lines 5-27sug, and the expression levels of SbNRT2-3, SbNRT2-4 and SbNRT3-2 were significantly reduced in sorghum aphid infested leaves. Overall, genome-wide identification, expression and DNA variation analysis of NRT2/3 gene family of Sorghum bicolor provided a basis for elucidating the high efficiency of sorghum in nitrogen utilization.
Nitrate Transporters ; Nitrates/metabolism* ; Sorghum/metabolism* ; Anion Transport Proteins/metabolism* ; Phylogeny ; Protein Sorting Signals/genetics* ; Nitrogen/metabolism* ; DNA ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism*

Biomechanical model of musculoskeletal system has accurate human anatomy and good biological fidelity. It can accurately and effectively reveal the biomechanical state and predict the internal mechanical response of musculoskeletal system. Therefore, it has been widely used in biomechanical study of musculoskeletal system, diagnosis and treatment of bone diseases, implant optimization design and preoperative planning. In 2021, the latest advances in biomechanical modeling method of musculoskeletal system mainly included three aspects, i.e., individualized finite element modeling, statistical model modeling and musculoskeletal system modeling. On this basis, the latest relevant literatures were summarized in this review to illustrate the progress and main applications of the above modeling method, and the future development direction of musculoskeletal modeling was discussed.

Objective:To develop an online interactive cytopathological training program, and to evaluate it for improving the cytopathological diagnostic ability of endoscopists in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreas.Methods:A total of 5 500 cytopathological images were collected from 194 patients with pancreatic solid mass who underwent EUS-FNA in Nanjing Drum Tower Hospital from August 2018 to August 2019. The cell type in each cytopathological picture was labeled by senior cellular pathologists, which was used to build a learning and testing platform for online interactive cytopathological training. Five endoscopists without cytopathological background were invited to participate in this training. Sensitivity, specificity, positive predictive value and negative predictive value of endoscopists in differential diagnosis of cancer and non-cancer before and after training were compared to evaluate the effect of the online interactive cytopathological training program on improving the ability of endoscopists in diagnosis of cytopathology.Results:A cytopathological training platform for endoscopists to learn and take online test was successfully built. Before training, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of diagnosis of cancer and non-cancer for endoscopists were 0.55 (95% CI: 0.53-0.58), 0.32 (95% CI: 0.30-0.35), 0.43 (95% CI: 0.41-0.45), 0.44 (95% CI: 0.41-0.47) and 0.43 (95% CI: 0.42-0.45), respectively. After training, the above indicators were 0.96 (95% CI: 0.95-0.97), 0.70 (95% CI: 0.68-0.73), 0.74 (95% CI: 0.72-0.76), 0.95 (95% CI: 0.94-0.96) and 0.81 (95% CI: 0.80-0.83), respectively, which were significantly improved compared with those before ( P<0.001). Conclusion:The online interactive cytopathological training program can improve the understanding and diagnostic ability of endoscopists in pancreatic cytopathology, help to implement rapid on-site evaluation in the process of EUS-FNA, and improve the diagnostic efficiency of EUS-FNA.

Objective:To evaluate the safety and feasibility of double endoscopic bypass, namely endoscopic ultrasound-guided gastroenterostomy (EUS-GE) combined with endoscopic ultrasound-guided biliary drainage (EUS-BD), for malignant gastric outlet and biliary obstruction.Methods:A retrospective analysis was conducted on data of 10 patients with malignant gastric outlet and biliary obstruction who were not suitable for surgery or endoscopic retrograde cholangiopancreatography (ERCP) and treated by double endoscopic bypass in Nanjing Drum Tower Hospital from August 2017 to October 2020. The completion of therapy, clinical efficacy and post-procedure adverse events were analyzed.Results:Ten patients with different malignant cancer successfully underwent EUS-GE and EUS-BD, with procedure time of 60.5±22.3 min (30-100 min). There were no postoperative adverse events. EUS-GE was clinically successful in all 10 cases. Of the 10 EUS-BD cases, 9 were clinically successful, and 1 did not meet the criteria of clinical success. The median follow-up was 71 (37-120) days. None of the 10 patients had recurrent gastric outflow tract obstruction or biliary tract obstruction.Conclusion:Double endoscopic bypass is feasible and effective for patients with malignant gastric outlet and biliary obstruction and without surgery or ERCP opportunity.