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.

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.

We summarize the most important advances in RNA delivery and nanomedicine. We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs. The fundamental properties of the key RNA members are described. We introduced recent advances in the nanoparticles to deliver RNA to defined targets, with a focus on lipid nanoparticles (LNPs). We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms, including the treatment of different types of cancer. This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology.

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.

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 explore the clinical features of acute diquat (DQ) poisoning, and further improve the awareness of acute DQ poisoning.Methods:A retrospective analysis was performed on the clinical data of patients with acute DQ poisoning diagnosed in the emergency department of the Second Hospital of Hebei Medical University from January 1, 2019 to December 31, 2021. The clinical data included age, gender, exposure routes, presence of pesticides (drugs) mixture poisoning, dosage of poison, the time from taking poisoning to admitting in the emergency department, clinical manifestations, laboratory data, treatment, hospital days, prognosis and survival days.Results:The number of cases who firstly complained of acute DQ poisoning in the past three years were 19 cases in 2019, 28 cases in 2020, and 51 cases in 2021. A total of 12 patients were excluded due to being diagnosed paraquat (PQ) poisoning by toxicology detection. Finally, 86 cases of acute DQ poisoning were included, including 80 cases of oral DQ poisoning, 1 case of intramuscular injection, 1 case of binocular contact and 4 cases of dermal exposure. In 80 cases of oral DQ poisoning, there were 70 cases of diquat poisoning alone (42 cases survived, 28 cases died) and 10 cases of pesticide mixture poisoning (6 cases survived, 4 cases died). The time from oral poisoning to admitting in the emergency department was 0.5-96.0 hours, with an average of (8.6±5.8) hours. The time of intramuscular injection poisoning to admitting in the emergency department was 3 hours. The time of dermal exposure to admitting in the emergency department was relatively long, with an average of 66.1 hours. The time from oral simple DQ poisoning to death was 12.0-108.0 hours, and the time from oral mixed DQ poisoning to death was 24.0-576.0 hours. A total of 70 patients with oral diquat poisoning alone presented various degrees of multiple organ injuries. All patients presented gastrointestinal symptoms such as nausea and vomiting. Renal injury and central nervous system injury were the most significant and closely related to the prognosis.Conclusions:Acute oral DQ poisoning can cause to multiple organ injuries, and the clinical manifestations are related to the dose of the poison. In severe cases, acute renal failure and refractory circulatory failure occur within 24 hours after poisoning, and severe central nervous system injury with disturbance of consciousness as the primary manifestation occurs within 36 hours, followed by multiple organ failure until death.

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.

Currently, invasive urodynamic testing is the " gold standard" for the diagnosis of bladder outlet obstruction (BOO). However, this test is invasive, easy to cause hematuria, urinary tract infection and other complications, the application conditions are limited.In order to solve this problem, various non-invasive methods to diagnose or predict BOO have been studied.The use of existing inspection indicators such as ultrasound measurement, penile cuff test, near infrared spectroscopy and other new non-invasive methods provide a new research direction for the non-invasive diagnosis of bladder outlet obstruction.

The safety of prophylactic vaccine is one of the key points both in clinical trials and evaluation. Based on the review practice of vaccine registration clinical trials in recent years, we puts forward a series of thoughts and suggestions on the common problems of safety study on vaccine, including the hypothesis of safety study, the consideration of inclusion/exclusion criteria and suspension/termination criteria for study; the routine requirements of safety study and some special issue such as medical laboratory test index, vaccine virus shedding and safety of adjuvant, and further clarifies the requirements of safety observation on sequential enrollment; also emphasized the scientific judgment of causality and the quality of safety monitoring. It can be used for reference by vaccine researchers and to explore appropriate solutions to promote vaccine research & development and risk control in China.

The safety of prophylactic vaccine is one of the key points both in clinical trials and evaluation. Based on the review practice of vaccine registration clinical trials in recent years, we summarized the common problems in safety analysis and report and accordingly puts forward a series of thoughts and suggestions, including discussing the role of statistics in safety analysis, putting forward the framework of safety analysis and report involved analysis content, analysis index and analysis dimension, in which attention is paid to the severity analysis; emphasizing the initiative analysis on risk signal and encouraging the evidence-based initiative safety evaluation. At the same time, this paper discusses the basic principles of the presentation of safety data in the package inserts, as well as the comprehensive consideration of the safety data of each phase of the trial and different subjects. It can be used for reference by sponsor to promote vaccine clinical research and evaluation in China.