[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。

OBJECTIVE: This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies. METHODS: Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model. RESULTS: A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM mortality was significantly associated with carbon monoxide. CONCLUSION High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
Diabetes Mellitus, Type 2/epidemiology* ; China/epidemiology* ; Humans ; Risk Factors ; Spatio-Temporal Analysis ; Air Pollutants/analysis* ; Socioeconomic Factors ; Bayes Theorem ; Female ; Male ; Middle Aged

To investigate the clinical utilization of Rituximab biosimilar (Rituximab injection) in order to provide references for evaluating its rationality and economic value in clinical application.

Objective To study the differences in living habit and blood biochemical indicators of male elderly people at different age groups in a"regional longevity"gathering area in Chongqing and the high fre-quency variation of mitochondrial DNA(mtDNA)in the elderly people(≥90 years old).Methods The male elderly people aged ≥60 years old in a"regional longevity"gathering area in Chongqing were randomly select-ed as the study subjects and divided into the group A(60-＜70 years old),group B(70-＜80 years old),group C(80-＜90 years old)and group D(≥90 years old).The differences of vegetable and fruit consump-tion,dairy bean consumption,outdoor activities,sleep time and blood biochemical indexes were compared a-mong different age groups.Then peripheral blood in the above subjects was collected for extracting mtDNA and sequencing.The meaningful mtDNA mutations between the various groups and group D were found out by the bioinformatics analysis.Results There were no statistically significant differences in consumption of vegetables and fruits,consumption of dairy beans,outdoor activities and sleep duration among different age groups(P＞0.05).There were statistically significant differences in erythrocyte and creatinine of blood bio-chemical indexes among the partial groups(P＜0.05).The mitochondria mutation analysis found 4 105 mtD-NA mutation sites,mainly single base mutation,the most common mutation was T＞C(22.57％),followed by C＞T(19.82％)and A＞G(19.36％).The average mutation rate of mtDNA in the group D was the high-est(8.392％),in which 3 mtDNA variants were found to have significant differences between different age groups and group D(P＜0.1),including mtDNA5396-5411CAACGTAAA＞C,mtDNA5414A＞T and mtD-NA5417G＞T.Conclusion There was no significant difference in the living habits of male elderly people of different ages.The mutation rate of mtDNA in the advanced age group was the highest.mtDNA5396-5411CAACGTAAA＞C,mtDNA5414A＞T and mtDNA5417G＞T variations may be related to"regional lon-gevity".

Objective:To investigate the effect of childhood trauma on non-suicidal self-injury (NSSI) behavior in patients with depression.Method:Embase, PubMed, Cochrane Library, PsycINFO, China National Knowledge Infrastructure, Wanfang Data and China Biology Medicine dis were searched from inception to March 2024 for cross-sectional, case-control and cohort studies on childhood trauma and NSSI in patients with depression. Two researchers independently screened studies, extracted data, and assessed quality. The effect indicators were the odds ratio ( OR) of childhood trauma and school bullying to NSSI in the depressed population and the mean difference ( MD) of the childhood trauma subscale scores between the depressed population with and without NSSI. Meta-analysis was performed using Review Manager 5.3 and Stata17 software. Results:A total of 29 articles with 5 095 depressed patients were included. Childhood trauma was significantly associated with NSSI in patients with depression ( OR=2.91, 95% CI=2.01-4.21). Various forms of childhood trauma were related to NSSI behaviors in depressive patients: physical abuse ( MD=0.77, 95% CI=0.47-1.06), emotional abuse ( MD=2.99, 95% CI=2.10-3.88), physical neglect ( MD=1.17, 95% CI=0.47-1.87), emotional neglect ( MD=2.59, 95% CI=1.82-3.36), and sexual abuse ( MD=0.35, 95% CI=0.19-0.51). Additionally, school bullying among extra-family factors was identified as a risk factor for NSSI ( OR=2.16, 95% CI=1.46-3.18). Conclusion:Childhood trauma is a risk factor for NSSI behaviors in patients with depression. Different types of childhood trauma within the family, including various forms of abuse and neglect, and school bullying outside the family are related to NSSI behaviors in this population.

Aim To investigate the mechanism by which sufentanil(Suf)improved hypoxia-reoxygen-ation(H/R)-induced myocardial cell injury by regula-ting hypoxia inducible factor-1α(HIF-1α)and KC-NQ1 opposite strand/antisense transcript 1(Kcnq1ot1).Methods Bioinformatics analysis was conducted to predict the interaction between HIF-1αand Kcnq1ot1.Subsequently,H9c2 cells were divided into multiple treatment groups:Ctrl group,H/R group,and Suf group.Further grouping was based on different transfection conditions,including oe-HIF-1α group,oe-HIF-1α+Suf group,sh-HIF-1α group,and sh-HIF-1α+Kcnq1ot1 group.Cell viability was detected u-sing the MTT assay,cell apoptosis was detected using the TUNEL assay,and the concentrations of CK-MB and HBDH in cell supernatants were measured using ELISA.HIF-1α protein expression in cellswas deter-mined by Western blot,and the mRNA expression level of Kcnq1ot1 was measured by reverse transcription quantitative PCR(RT-qPCR).Additionally,a rat model of myocardial is chemia reperfusion was con-structed to evaluate the therapeutic potential of Suf for myocardial ischemia reperfusion injury in vivo.Results The results of bioinformatics analysis showed a direct interaction between HIF-1α and Kcnq1ot1.Compared with the Ctrl group,the H/R group showed significantly reduced H9c2 cell viability,increased cell apoptosis,and significantly upregulated concentrations of CK-MB and HBDH,along with significantly enhanced expres-sion of HIF-1α and Kcnq1ot1(all P＜0.05).When H9c2 cells were transfected with oe-HIF-1 α,cell via-bility further decreased,apoptosis was worsened,and CK-MB and HBDH concentrations further increased(all P＜0.05);however,these adverse effects were significantly inhibited when combined with Suf inter-vention(all P＜0.05).Additionally,compared with the H/R group,the sh-HIF-1α group showed signifi-cantly improved cell viability,reduced apoptosis and decreased CK-MB and HBDH concentrations(all P＜0.05);however,these improvements were partially re-versed upon transfection with Kcnq1ot1(all P＜0.05).Animal experiments confirmed that Suf could improve myocardial ischemia-reperfusion injury in myo-cardial ischemia-reperfusion injury rats.Conclusions Suf improves myocardial H/R injury by inhibiting the HIF-1α-Kcnq1ot1.

Objective:To analyze the clinical features and long-term prognosis of ANCA-associated vasculitis (AAV) patients with different onset ages.Methods:A total of 243 patients diagnosed with AAV at the First Affiliated Hospital to Nanjing Medical University from May 2009 to January 2025 were retrospectively analyzed. The patients were divided into the elderly group (age≥60 years old) and middle-aged and young patient group (age<60 years old) according to the age of onset. The baseline clinical characteristics and long-term prognosis of the two groups were compared, and the risk factors for progression to end-stage renal disease (ESRD) in elderly AVV patients were analyzed. The clinical characteristics and long-term prognosis of the two groups of patients were compared. The measurement data were analyzed by t-test or rank sum test, and the count data were analyzed by chi-square test. The risk factors for the progression of ESRD in elderly patients with AAV were analyzed by binary multivariate logistic regression. Results:A total of 243 AAV patients were included, among which 174 cases were microscopic polyangiitis (MPA) and 69 cases were granulomatosis with polyangiitis (GPA). In 157 elderly patients, with 72 cases female, 84.1%(132 cases) had MPA. Compared with young and middle-aged patients, renal involvement is more common in elderly patients with AAV [(eldrly group 133 cases, 84.7%) vs. middle-aged and young patient group: 61 cases(70.9%), χ2=6.557, P=0.010]. The proportion of patients with hypertension, thrombosis, stroke, coronary heart disease, and COPD was higher compared to non-elder patients ( P<0.05). Elderly patients with AAV have higher levels of IgA and serum creatinine. Kaplan-Meier survival analysis showed that compared with young and middle-aged patients, elderly AAV patients had a higher all-cause mortality rate within 1 year after disease onset and a higher risk of progressing to ESRD within 1 year ( P<0.05), while the levels of IgM, C3, C4, albumin, and hemoglobin were lower ( P<0.05). 86 patients were middle-aged and young patients, with 54 cases were female and 51.2%(44 cases) had GPA. Ear, nose, and throat involvement was more common than elder patients[elderly group: 26 cases(16.2%) vs. middle-aged and young patient group: 31 cases(36.0%), χ2=10.864, P=0.001]. The median follow-up duration was 18 (7, 60) months. Kaplan-Meier survival analysis showed that compared with middle-aged and young patients, elderly AVV patients had a higher all-cause mortality rate within 1 year after disease onset and a higher risk of progression to ESRD within 1 year ( P<0.05). Multivariate logistic regression analysis revealed that baseline serum creatinine level [ OR(95% CI)=1.008(1.003, 1.012), P<0.001] was an independent risk factor for progression to ESRD in elderly patients. Conclusion:Elderly patients with AAV have more severe organ damage, higher all-cause mortality within one year, and a higher risk of progression to ESRD within one year after disease onset close monitoring of high-risk elderly patients should be strengthened.

Objective:To investigate the radioactivity levels and variation trends of 90Sr in drinking water and food around the Qinshan Nuclear Power Plant in operation. Methods:From 2012 to 2022, the source, factory, and tap water was collected within 30 km around the Qinshan Nuclear Power Plant during the wet and dry seasons (i.e., May and October, respectively) each year to determine the 90Sr concentration in water. According to the dietary habits of local residents, four kinds of food, including rice, cabbage, mullet, and crucian carp, were collected to determine and analyze the 90Sr radioactivity concentration in food using the bis-(2-ethylhexyl) phosphoric acid extraction chromatographic method. Results:From 2012 to 2022, the 90Sr radioactivity concentrations in the source, factory, and tap water around the Qinshan Nuclear Power Plant ranged from 3.73 to 11.89 mBq/L, 2.95 to 9.83 mBq/L, and 3.12 to 8.70 mBq/L, respectively, showing nonsignificant fluctuations over the years. The 90Sr radioactivity concentrations in rice, cabbage, mullet, and crucian carp ranged from 0.02 to 0.46 Bq/kg (dry weight), 0.26 to 1.07 Bq/kg (fresh weight), 0.38 to 1.05 Bq/kg (fresh weight), and 0.08 to 1.32 Bq/kg (fresh weight), respectively, all below the national standard limits. Conclusions:From 2012 to 2022, the 90Sr radioactivity levels in drinking water and food around the Qinshan Nuclear Power Plant were at the background level and remained stable.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.