Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Objective: To identify the effective needs of college students for dietary nutrition health education content, so as to provide a scientific basis for optimizing the health education strategies in colleges. Methods: The literature analysis method, focus group interviews and Delphi expert consultation method were used to construct a survey questionnaire on dietary nutrition health education for college students. From January to March 2024, a total of 597 college students from six colleges in Shandong Province were selected through convenience sampling to complete the questionnaire independently by scanning the two dimensional code on questionnaire star. The Kano model was used to define the content demands of college students for dietary nutrition education, and the differences in demands were analyzed by calculating satisfied influence (SI) and dissatisfied influence (DSI). Results: The compiled questionnaire was divided into 7 dimensions and 25 items. The overall demand level analysis of college students included 3 essential attribute demands, namely, the recommended intake and various forms of dairy products (34.17%), the role of whole grains in health with their scientific intake forms and recommended amounts (31.99%), and the intake of beans (30.15%); 7 expected attribute demands included the introduction of recommended intensity of different activities (35.01%), how to achieve a healthy weight and the balance between diet and exercise (41.54%), the energy consumed by different exercises in a unit of time ( 38.36 %), the selection of healthy snacks (36.68%), the types of infectious diseases of the digestive system and how to prevent and control them (25.96%), the causes and judgments with manifestations of nutrition related diseases among college students ( 28.14 %), and the hotspots of attention on nutrition related diseases among college students (24.46%); 4 attractive attribute demands contained the introduction of the recommended activity levels for different periods such as daily and weekly (28.81%), the introduction of the importance of activities and the harm of prolonged sitting and ways to avoid it (28.64%), the nutritional value of animal foods and eating suggestions (23.45%), and the scientific intake suggestions for various processed animal foods (22.11%); the remaining were 11 attribute demands with no differences. In the quadrant diagram analysis, the demand items located in the maintenance zone, competitive advantage zone, improvement zone, and minor improvement zone were 5, 5, 8, and 7, respectively. Conclusions College students have different demands in dietary nutrition health education, and whether these demands are met affects their satisfaction in different ways. Among them, education on the intake of dairy products, whole grains, and beans has the greatest impact on satisfaction.

OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

ObjectiveTo establish and characterize an inducible， CD4+ T cell-specific ablation mouse model （CD4-iDTR） using the Cre-loxP and diphtheria toxin receptor （DTR） systems， and to evaluate its depletion efficacy and specificity. MethodsCD4-iDTR mice were generated through cross-breeding， with genotypes confirmed via PCR-based screening. Mice were categorized into an untreated （control） group and a diphtheria toxin （DT） induction group. Flow cytometry was employed to compare the baseline distribution of CD4⁺ T cells between untreated CD4-iDTR and wild-type C57BL/6 mice.In the DT group， CD4⁺ T cell ablation was induced by subcutaneous DT administration. The depletion efficiency in skin tissues and skin-draining lymph nodes （sdLNs） was quantified at 24 h and 1 week post-injection. Furthermore， the proportions of neutrophils， macrophages， dendritic cells， and other CD11b⁺ immune cell subsets in the skin were monitored to assess the model specificity. ResultsGenomic profiling confirmed the successful generation of the CD4-iDTR line. Under steady-state conditions， no significant differences were observed in the frequency or absolute number of CD4⁺ T cells in the skin and sdLNs between CD4-iDTR and C57BL/6 mice （P>0.05）. Following DT induction， the CD4⁺ T cell population in the skin exhibited decline within 24 h and 1 week （P<0.05）， whereas the CD4⁺ T cell counts in sdLNs remained stable. The percentages of cutaneous neutrophils， macrophages， and other CD11b⁺ myeloid populations were not significantly altered following DT treatment （P>0.05）. ConclusionThe CD4-iDTR mouse model is successfully established and bred， achieving efficient， specific， and inducible ablation of cutaneous CD4⁺ T cells without significant interference with the skin immune microenvironment. This model serves as an ideal experimental tool for investigating skin-specific immunological mechanisms.

ObjectiveTo analyze the characteristics and life loss of injury-related deaths among the registered residents in Anji County from 2015 to 2024, and to provide a reference for conducting targeted injury prevention and control efforts. MethodsData on injury-related deaths among the registered residents in Anji County from 2015 to 2024 were collected from the Chronic Disease Surveillance and Management System of Zhejiang Province. Indicators including the crude mortality rate (CMR), standardized mortality rate (SMR), proportion, potential years of life lost (PYLL), average years of life lost (AYLL) and potential years of life lost rate (PYLLR) were calculated. The annual trends in injury mortality were evaluated using average annual percent change (AAPC). ResultsFrom 2015 to 2024, a total of 3 800 injury deaths were reported in Anji County, accounting for 11.94% of all deaths and ranking as the fourth leading cause of death. The CMR was 80.65/100 000 and showed an upward trend (AAPC=3.53%, P=0.003), while the SMR was 50.68/100 000 with no significant trend (AAPC=-1.47%, P=0.196). The CMR was higher in males (95.03/100 000) than in females (66.49/100 000). The top five causes of injury-related deaths were accidental falls, traffic accidents, suicide, drowning and accidental poisoning. The top two injury-related causes of death varied by age group: for the 0‒<15 age group, they were accidental falls, traffic accidents (with drowning tied for second place); for the 15‒<45 age group, they were traffic accidents and suicide; for the 45‒<65 age group, they were traffic accidents and accidental falls; and for the 65‒105 age group, they were accidental falls and traffic accidents. From 2015 to 2024, the total PYLL due to injury deaths was 47 464.00 person-years, the AYLL was 12.49 years, and the PYLLR was 10.07‰. ConclusionFrom 2015 to 2024, the injury crude mortality rate in Anji County was relatively high and showed an upward trend. Targeted interventions based on demographic characteristics and injury types should be implemented to reduce injury mortality.

AIM: To analyze the current status, research hotspots, and development trends of international studies on ocular surface microbiota based on bibliometrics.METHODS: Leveraging the Web of Science database, we conducted a targeted literature search on ocular surface flora. The retrieved data were meticulously screened and weighted to enhance relevance. The bibliometric analysis delved into publication trends, authorship patterns, institutional collaborations, and pivotal research themes. Employing Cite Space software, we visually dissected the landscape of institutional and national partnerships, citation impact, keyword co-occurrences, keyword clustering dynamics, and the emergence of new research trends.RESULTS: A total of 3 884 publications were ultimately included, with an overall upward trend in the number of publications in the field of ocular surface microbiota from 2003 to 2023, with the most rapid growth occurring from 2019 to 2022. The top three regions/countries by publication volume are the United States(1 039 papers), China(570 papers), and India(302 papers). The top three authors by publication volume are Willcox Mark(48 papers), Sharma Savitri(33 papers), and Fleiszig Suzanne M.J(27 papers). The top three institutions by publication volume, all from the United States, are the University of California, L.V. Prasad Eye Institute, and Harvard University. The citation network map of the literature includes 801 nodes and 1 508 connections, with the most frequently cited document being Temporal Stability and Composition of the Ocular Surface Microbiome. The top 5 keywords by frequency of occurrence are, in order, keratitis, bacterial flora, identification, inflammation, and endophthalmitis. The keyword clustering analysis yielded a total of 8 clusters, which are specifically reflected in three aspects: ocular-related diseases, the relationship between ocular surface microbiota and ocular surface structures, and detection methods for ocular surface microbiota. The keyword with the highest burst strength is ciprofloxacin. Keywords that have emerged in recent years and continue to the present include diversity, gut microbiome, and ocular surface microbiome.CONCLUSION: Currently, the study of ocular surface microflora is gaining momentum globally, with a particular focus on the diversity of microflora, the composition of the core microbiome, and its impact on ocular diseases. In the future, research should concentrate on elucidating the functional metabolism of the ocular surface microflora and further investigate the causality and mechanisms by which changes in the ocular surface microflora are related to diseases.

ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals