[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

Myopia has become a growing public health issue globally, characterized by an earlier age of onset and a rising annual incidence rate, particularly among adolescents. Repeated low-intensity red light therapy(RLRL)has gained widespread attention in recent years as an emerging non-invasive intervention, showing promise for controlling myopia. This article examines the role of the PI3K/AKT signaling pathway in RLRL,specifically advances in promoting choroidal thickening via the phosphorylation mechanism of endothelial nitric oxide synthase(eNOS). Choroidal thickening is recognized as a critical part of myopia control. Activation of the PI3K/AKT/eNOS-NO signaling pathway may attenuate axial elongation by enhancing choroidal blood flow and nutrient supply. Although certain basic and clinical studies have supported this mechanism, many unresolved issues still remain, such as the specific mechanisms of RLRL action, its safety, and its applicability in different populations. This article systematically reviews the relevant research progress, aiming to provide a valuable reference for future studies and explore the application prospects of RLRL in myopia prevention and control.

ObjectiveIdentification and analysis, animal regression test, and drug susceptibility study were conducted on a pathogenic strain causing diarrhea in cynomolgus monkeys, aiming to provide a practical basis for the clinical treatment of Citrobacter freundii. MethodsFresh fecal samples were collected from nine diarrheal cynomolgus monkeys and streaked on Salmonella-Shigella (SS) medium, LB medium, and Columbia blood agar medium, and incubated at 37 ℃ for 24 h. Subsequently, the isolated strain was identified by colony morphology observation, Gram staining, biochemical tests and 16S rRNA gene sequencing, and PCR was used to detect its major virulence genes. After propagation, the isolate was intragastrically administered to healthy cynomolgus monkeys and C57BL/6 mice for animal regression tests to evaluate its pathogenicity. Finally, the disk-diffusion method was used to detect the antimicrobial susceptibility of the isolate. ResultsA single bacterial strain, designated MF071743, was isolated from 9 fecal samples collected from diarrheal cynomolgus monkeys. The isolate formed pink, smooth, round colonies on SS medium; translucent, smooth, moist, shiny colonies with neat edges on LB medium; and smooth, moist, off-white colonies on Columbia blood agar medium. Gram staining revealed that the isolate was a Gram-negative, spore-free short bacillus. Biochemical tests showed that the isolate was positive for motility test, mannitol test, hydrogen sulfide test, methyl red test, citrate utilization test, gas production from glucose test, raffinose test, sorbitol test, and D-xylose test, but negative for phenylalanine test, gluconate test, indole test, Voges Proskauer (VP) test, urease test, lysine test, ornithine test, and adonitol test. The results of 16S rRNA gene sequencing showed that the gene sequence similarity between strain MF071743 and Citrobacter freundii was 99.0%. PCR results showed that this strain carries genes encoding the urease accessory proteins UreD, UreE, and UreF. Animal intragastric administration assays demonstrated that the strain caused loose stools in cynomolgus monkeys, and all C57BL/6 mice died within 72 h. Drug susceptibility test results indicated that the isolate was sensitive to 16 antibiotics, including ceftriaxone, amikacin, gentamicin, ceftazidime, and levofloxacin, while it exhibited resistance to 5 antibiotics, including ampicillin, cefazolin, vancomycin, erythromycin, and cephalexin. ConclusionA strain of Citrobacter freundii with certain drug resistance was isolated from the feces of diarrheal cynomolgus monkeys. The results of this study provide a reference for the diagnosis and treatment of gastrointestinal diseases in captive laboratory monkeys.

OBJECTIVE To establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

OBJECTIVES: To investigate the chain mediating role of family care and emotional management in the relationship between social support and anxiety among rural primary school students. METHODS: A questionnaire survey was conducted among students in grades 4 to 6 from four counties in Hunan Province. Data were collected using the Social Support Rating Scale, Family Care Index Scale, Emotional Intelligence Scale, and Generalized Anxiety Disorder -7. Logistic regression analysis was used to explore the influencing factors of anxiety symptoms. Mediation analysis was conducted to assess the chain mediating effects of family care and emotional management between social support and anxiety. RESULTS: A total of 4 141 questionnaires were distributed, with 3 874 valid responses (effective response rate: 93.55%). The prevalence rate of anxiety symptoms among these students was 9.32% (95%CI: 8.40%-10.23%). Significant differences were observed in the prevalence rates of anxiety symptoms among groups with different levels of social support, family functioning, and emotional management ability (P<0.05). The total indirect effect of social support on anxiety symptoms via family care and emotional management was significant (β=-0.137, 95%CI: -0.167 to -0.109), and the direct effect of social support on anxiety symptoms remained significant (P<0.05). Family care and emotional management served as significant chain mediators in the relationship between social support and anxiety symptoms (β=-0.025,95%CI:-0.032 to -0.018), accounting for 14.5% of the total effect. CONCLUSIONS Social support can directly affect anxiety symptoms among rural primary school students and can also indirectly influence anxiety symptoms through the chain mediating effects of family care and emotional management. These findings provide scientific evidence for the prevention of anxiety in primary school students from multiple perspectives.
Humans ; Female ; Male ; Social Support ; Anxiety/etiology* ; Child ; Students/psychology* ; Emotions ; Logistic Models

OBJECTIVES: The gut microbiota plays a crucial role in the pathophysiology of various types of diabetes. However, the causal relationship between them has yet to be systematically elucidated. This study aims to explore the potential causal associations between gut microbiota and diabetes using a two-sample Mendelian randomization (MR) analysis, based on multiple taxonomic levels. METHODS: Eligible instrumental variables were extracted from the selected genome-wide association study (GWAS) data on gut microbiota. These were combined with GWAS datasets on type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) to conduct forward MR analysis, sensitivity analysis, reverse MR analysis, and validation of significant estimates. Microbial taxa with causal effects on T1D, T2D, and GDM were identified based on a comprehensive assessment of all analytical stages. RESULTS: A total of 2 179, 2 176, and 2 166 single nucleotide polymorphisms (SNP) were included in the MR analyses for gut microbiota with T1D, T2D, and GDM, respectively. MR results indicated causal associations between: Six microbial taxa (Eggerthella, Lachnospira, Bacillales, Desulfovibrionales, Parasutterella, and Turicibacter) and T1D; 9 microbial taxa (Verrucomicrobia, Deltaproteobacteria, Actinomycetales, Desulfovibrionale, Actinomycetaceae, Desulfovibrionaceae, Actinomyces, Alcaligenaceae, and Lachnospiraceae NC2004 group) and T2D; 10 microbial taxa (Betaproteobacteria, Coprobacter, Ruminococcus2, Tenericutes, Clostridia, Methanobacteria, Mollicutes, Methanobacteriales, Methanobacteriaceae, and Methanobrevibacter) and GDM. CONCLUSIONS This study identified specific gut microbial taxa that may significantly increase or decrease the risk of developing diabetes. Some findings were fully replicated in independent validation datasets. However, the underlying biological mechanisms of these causal relationships warrant further investigation through mechanistic studies and population-based research.
Gastrointestinal Microbiome/genetics* ; Humans ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Diabetes Mellitus, Type 2/genetics* ; Diabetes Mellitus, Type 1/genetics* ; Female ; Polymorphism, Single Nucleotide ; Diabetes, Gestational/genetics* ; Pregnancy