ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

Objective To analyze the current status,research hotspots and development trends in the field of immune responses in the microenvironment after spinal cord injury(SCI). Methods Literatrues about immune responses in the microenvironment after SCI were searched from CNKI and the Web of Science Core Collection,from inception to March,2024.VOSviewer and CiteSpace were used to conduct a vi-sual analysis of authors,countries,institutions,journals,co-cited references and keywords. Results A total of 152 Chinese and 455 English studies were included.The number of publications increased annually,and China and the United States were leading research efforts in this field.In the Chinese literature,Zhu Yue was the most prolific author,and China Medical University was the leading institution.In the English literature,Phil-lip Popovich was the most prolific and highly cited author,and Ohio State University was the leading institution.Journal of Neuroscience and Experimental Neurology were identified as key journals.The research hotspots in both languages focused on immune activation,inflammatory response and functional recovery.Researches on stem cell transplantation,macrophage and traditional Chinese medicine were particularly prominent in the regu-lation of immune responses after SCI. Conclusion Immune responses in the microenvironment have emerged as a central focus in SCI research.The emphasis of current researches is shifting from mechanistic exploration to the investigation of immunomodulatory strate-gies,with several cutting-edge technologies showing significant potential in this regard.Moving forward,increas-ing collaboration across regions and institutions are essential to promote information sharing,accelerate scientific progress,and facilitate clinical translation,ultimately enhance patient rehabilitation outcomes.

Objective:To discuss the postoperative survival of the gastric cancer patients with different expression levels of myeloid ecotropic viral integration site 1(MEIS1),and to analyze the predictive value of MEIS1 expression in the prognosis evaluation of gastric cancer.Methods:In a gastric cancer survival cohort,215 patients who underwent radical gastrectomy were selected.Immunohistochemical staining was used to detect the expression levels of MEIS1 in both gastric cancer and adjacent normal tissues.The relationship between expression level of MEIS1 and the clinicopathological characteristics of the patients were analyzed by x2 test or Fisher's exact probability method;survival curves were plotted by Kaplan-Meier method;the differences in survival of the patients between MEIS1 high expression group and MEIS1 low expression group were compared by Log-rank test;multivariate Cox proportional hazards regression model was used to calculate the hazard ratios(HR)and 95％confidence intervals(CI)to assess the relationship between MEIS1 expression level and the survival of the gastric cancer patients.Results:The immunohistochemical staining result showed that the expression level of MEIS1 in gastric cancer tissue was decreased.The univariate analysis results showed that the patients with high MEIS1 expression had a longer overall survival than those with low expression(P=0.049),and had a better prognosis.The multivariate Cox proprotional hazards regression analysis results showed that the low MEIS1 expression and high TNM stage were the independent risk factors for poor prognosis of the patients with gastric cancer(HR=1.577,95％CI:1.011-2.460,P=0.045;HR=2.709,95％CI:1.708-4.297,P＜0.001).Conclusion:The gastric cancer patients with low expression of ME1S1 have a shorter postoperative overall survival;MEIS1 is a promising biomarker for prognosis assessment of the patients after radical gastrectomy.

AIM:To study the mechanism of Sihei-fang(SHF)in improving pigment deficiency disease(PD)by combining network pharmacology and me-tabolomics.METHODS:Using zebrafish embryos with pigment deficiency disease induced by 1-phe-nyl-2-thiourea(PTU)as an animal model,the ef-fects of SHF extract(0.01,0.02,0.04 mg/mL)on the morphology,melanin area,tyrosinase activity,and melanin content of zebrafish embryos were an-alyzed.Ultra high performance liquid chromatogra-phy-mass spectrometry(UHPLC-MS)was used to screen differential metabolites and obtain relevant metabolic pathways in the SHF treatment of mela-nin deficient zebrafish embryos model.Network pharmacology was used to obtain key targets for SHF treatment of PD and conduct KEGG pathway enrichment analysis.Import The identified differen-tial metabolites and SHF PD intersection targets were imported into the Metscape plugin,to estab-lish a"metabolite reaction enzyme gene"network,and search for key metabolites,targets,and meta-bolic pathways.RESULTS:SHF treatment could in-crease the formation of zebrafish melanin,activate tyrosinase activity,and increase melanin content.Metabolomics analysis obtained 54 differential me-tabolites,and metabolic pathway analysis was con-ducted on these metabolites,involving the biosyn-thesis of phenylalanine,tyrosine,and tryptophan,glycerol phospholipid metabolism,tyrosine metab-olism,linoleic acid metabolism,and aminoacyl tRNA biosynthesis pathways.Network pharmacolo-gy had obtained 55 cross targets of components and diseases.KEGG involved pancreatic cancer,TNF,cancer and other signal pathways.The joint analysis of metabolomics and network pharmacolo-gy identified four key targets:COMT,CYP1B1,TYR,and ALDH2;three key metabolites:L-tyrosine,ho-movanllate,L-lysine;three important metabolic pathways:tyrosine metabolism,valine/leucine/iso-leucine degradation,and lysine metabolism.CON-CLUSION:SHF has a good improvement effect on PD,and combined with metabolomics and network pharmacology,SHF may enhance its influence on the tyrosine metabolism pathway by regulating the metabolite L-tyrosine,thereby promoting the for-mation of melanin.

Nicotinamide mononucleotide (NMN) is an important precursor in conversing nicotinamide adenine dinucleotide (NAD +) in the body. By elevating NAD + level in the body, NMN enhances the hydrogen transfer function of NAD + in biological processes, promotes the synthesis of proteins and polysaccharides, improves substance transportation and regulatory efficiency, and enhances metabolic functions. Specifically, in central nervous system disease, NMN exerts neuroprotective effect through antioxidation, anti-inflammation, mitochondrial protection, and prevention of neuronal and axonal degeneration. This review focuses on the therapeutic role of NMN in common central nervous system diseases and their neuroprotective mechanisms, so as to further understand the role of NMN in central nervous system diseases, and provide references for predicting therapeutic targets and screening therapeutic drugs for central nervous system diseases.

Objective:To identify the differentially expressed long-chain non-coding RNA(lncRNA) and mRNA using ribonucleic acid sequencing(RNA-seq), and construct a competing endogenous RNA(ceRNA) regulatory network in mice with sepsis-associated encephalopathy.Methods:Ten clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups( n=5 each) using a random number table method: sham operation group(group Sham) and sepsis group(group Sepsis). Sepsis was induced by cecal ligation and puncture(CLP) in group Sepsis, while group Sham only underwent laparotomy without CLP. Morris water maze test and contextual fear conditioning test were performed to detect the cognitive function on 1 day before CLP and 3 days after CLP. Three mice were randomly sacrificed in group Sham, and 3 mice with the worst results in the cognitive function test were sacrificed in group Sepsis. The hippocampal tissues were obtained for RNA-seq via the BGISEQ-500 platform, and the differentially expressed mRNA and lncRNA were identified. The differentially expressed mRNAs and lncRNAs were visualized and analyzed by Dr. Tom platform provided by Shenzhen BGI Technology Service Co., Ltd., and the ceRNA regulatory network was constructed using the online visualization tool Cytoscape software. Results:Compared with group Sham, the escape latency was significantly prolonged, and the percentage of time of staying at the target quadrants and percentage of time spent freezing were decreased in group Sepsis( P<0.05). A total of 62 differentially expressed lncRNAs were obtained from RNA-seq, of which the expression of 45 lncRNAs was up-regulated and the expression of 17 lncRNAs was down-regulated.There were 282 differentially expressed mRNAs identified from RNA-seq, of which the expression of 173 mRNAs was up-regulated, and the expression of 109 mRNAs was down-regulated.Gene Ontology enrichment analysis revealed that the differentially expressed mRNAs were involved in biological processes such as memory, learning or memory, inflammatory responses, regulation of aging-related behavioral decline, and regulation of synaptic plasticity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that differentially expressed mRNAs were enriched in IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway and etc. KDA analysis was performed on the differentially expressed mRNAs to identify the key driver genes, and the results showed that Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 were the key SAE genes.A competing endogenous RNA regulatory network was successfully constructed based on 9 lncRNAs, 28 mRNAs and 134 miRNAs in the hippocampus of mice with SAE. Conclusions:The results of RNA-seq find that 10 mRNAs including Ch25h, Il6ra, Lcn2, Sgk1, Nr4a3, Osm, Saa3, Ccl7, Sqle, Dhcr24 and lncRNAs such as Rian, Gm35874 and Gm34347 are key genes regulating SAE in mice. Meanwhile, a ceRNA regulatory network based on lncRNA-miRNA-mRNA is successfully constructed in the hippocampus of mice with SAE.

Objective:To observe whether Cyclosporin A(CSA)treatment may protect acute pancreatitis(AP)mice and related cardiac injury by consequent attenuation of systemic inflammation via regulating macrophage polarization.Methods:RAW264.7 cells were used for in vitro experiments,stimulated with 0,5,10 and 20 nmol/L CSA for 24 hours,and M2 markers were detected by flow cytometry.C57BL/6J mice were used for experiments in vivo.The mice were randomly divided into 3 groups(n=15):control group,AP model group(intraperitoneal injection of L-arginine)and AP+CSA(20 mg/kg)group,CSA was administered in a pre-treated manner.ELISA kit was used to detect the indexes of pancreatic and myocardial injury in mice;HE staining was used to detect the pathological changes of pancreas and heart tissue;TUNEL method was used to detect apoptosis in tissue sections;CETSA was used to determine the relationship between CSA and PKM;The expressions of PKM2,HIF1α,p-STAT1 and p-STAT6 were detected by Western blot.Results:CSA increased the number of M2 macrophages and decreased the number of M1 macrophages in a dose-dependent manner in vitro.CSA pretreatment significantly improved pancreatic structure and myocardial injury in AP mice,decreased pancreatic histopathological score and serum amylase,lipase,TNF-α,CK-MB,LDH and cTnT levels.CSA pretreatment significantly reduced the number of TUNEL positive cells in myocardium of AP mice.Flow cytometry analysis showed that CSA pretreatment significantly inhibited the proportion of CD11c+F4/80+ and promoted the ratio of CD206+F4/80+ in AP induced myocardial macrophages.CETSA analysis showed that PKM2 was the target of CSA.Conclusion:CSA can significantly improve the severity of L-arginine-induced cardiac damage in AP model mice,and its mechanism of action is related to increasing the number of M2 macro-phages and inhibiting the production of proinflammatory cytokines.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Objective:To observe the incidence of syncope in patients with acute and critical cardiovascular diseases and to explore the risk factors of death.Methods:925 cases of acute heart failure, acute myocardial infarction, pulmonary embolism, arrhythmia and aortic dissection rupture who participated in Prospective, Multi-CenterRegistered Research Project for Chinese Syncope Patients from March 2018 to March 2020, admitted to the department of emergency of Nanyang Second General Hospital were selected as the research objects. The incidence and mortality of syncope were recorded, and the patients were divided into syncope group and non-syncope group according to whether they were accompanied by syncope or not. The incidence of syncope in male and female patients with different cardiovascular critical diseases, the age and mortality of cardiovascular critical patients with syncope or not were analyzed and compared. Multivariate Logistic regression analysis was used to analyze the risk factors of death, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of risk factors on the prognosis of patients.Results:The incidence of syncope in 5 kinds of cardiovascular critical patients from high to low was: acute myocardial infarction 3.03% (28/925), arrhythmia 2.70% (25/925), pulmonary embolism 1.51% (14/925), aortic dissection rupture 1.41% (13/925), acute heart failure 0.65% (6/925), with statistically significant differences ( χ2 = 10.765, P = 0.010). There was no significant difference in the incidence of syncope between male and female patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia and acute heart failure. The age of patients with aortic dissection rupture, acute myocardial infarction and arrhythmia in syncope group were significantly higher than those in non-syncope group [aortic dissection rupture (years old): 66.29±15.64 vs. 57.63±14.23, acute myocardial infarction (years old): 69.55±15.13 vs. 62.10±15.75, arrhythmia (years old): 70.48±14.93 vs. 60.29±16.31, all P < 0.05]. The mortality of patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia, acute heart failure in syncope group were significantly higher than those in non-syncope group [pulmonary embolism: 5.81% (5/86) vs. 0.95% (8/839), aortic dissection rupture: 4.65% (4/86) vs. 0.60% (5/839), acute myocardial infarction: 4.65% (4/86) vs. 1.19% (10/839), arrhythmia: 2.33% (2/86) vs. 0.95% (8/839), acute heart failure: 2.33% (2/86) vs. 0.60% (5/839), all P < 0.05]. Multivariate Logistic regression analysis showed that age [odds ratio ( OR) = 2.158, 95% confidence interval (95% CI) was 0.921-4.785, P = 0.000], pulmonary embolism ( OR = 15.391, 95% CI was 8.904-27.314, P = 0.001), aortic dissection rupture ( OR = 13.079, 95% CI was 6.237-25.509, P = 0.000), acute myocardial infarction ( OR = 18.826, 95% CI was 10.420-32.921, P = 0.000), syncope ( OR = 4.940, 95% CI was 1.764-9.287, P = 0.000) were risk factors for the prognosis of patients with acute and critical cardiovascular diseases. ROC curve analysis showed that syncope had a certain predictive value for 28-day prognosis of patients [the area under the ROC curve (AUC) = 0.760, P = 0.000], when the cut-off value was 4.12, the sensitivity was 88.51%, the specificity was 78.05%, the positive predictive value was 81.31%, and the negative predictive value was 84.27%. Conclusions:Syncope is an independent risk factor of death in patients with acute and critical cardiovascular diseases. For patients with syncope as the chief complaint, we should quickly identify the types of acute and critical diseases and assess the risk of sudden death.

An expert consensus about the clinical diagnosis and treatment of dry eye was documented in 2013 by a corneal expert group of Chinese Ophthalmological Society.However, due to the rapid development of diagnostic and therapeutic devices of dry eye, researoh on dry eye has made significont progress in China since then.Consequently, the existing expert consensus cannot meet the needs of clinical practice.It is therefore urgent to develop a series of standardized diagnosis and treatment protocols, and publish a new consensus of experts and an operating guideline.At the same time, basic, clinical, and translational research on dry eye should be promoted to provide better services to the patients with dry eyes.On January 12, 2019 many experts in the field of dry eye in China held a panel discussion of dry eye study in Guangzhou to analyze the current development status and trends in the field of dry eye in China and abroad.In that meeting, opinions and recommendations were put forward based on a new understanding of the definition of dry eye, new concepts of dysfunctional dry eye, advances its diagnosis and classification, refinement and standardization of dry eye treatment, and the future development of dry eye research.