ObjectiveTo investigate the association between metabolic associated fatty liver disease （MAFLD） and the risk of atherosclerotic cardiovascular disease （ASCVD）， and to provide data support for the prevention and treatment of such metabolic-associated diseases in clinical practice. MethodsAn observation cohort was established for the workers of Kailuan who underwent physical examination for the first time from June 2006 to October 2007 and had complete liver assessment data， without the history of malignant tumor， MAFLD or ASCVD. According to the presence or absence of MAFLD， the patients were divided into non-MAFLD group with 67 565 patients and MAFLD group with 29 004 patients， and according to the presence or absence of ASCVD， the patients were divided into non-ASCVD group with 69 141 patients and ASCVD group with 481 patients. The group t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between the two groups. The χ² test was used for comparison of categorical data between the two groups. The life-table method was used to calculate the cumulative incidence rates of new-onset ASCVD and MAFLD； the Kaplan-Meier method was used to plot the survival curves of the cumulative incidence rates of ASCVD in the MAFLD group and the non-MAFLD group and the cumulative incidence rates of MAFLD in the ASCVD group and the non-ASCVD group， and the log-rank test was used for comparison of cumulative incidence rates between two groups. A multivariate Cox proportional-hazards regression model analysis was used to investigate the impact of MAFLD on the risk of ASCVD and the impact of ASCVD on the risk of MAFLD. ResultsCompared with the non-MAFLD group， the MAFLD group had significantly higher levels of body mass index （BMI）， waist circumference， systolic blood pressure （SBP）， diastolic blood pressure （DBP）， resting heart rate， alanine aminotransferase， uric acid （UA）， fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol， low-density lipoprotein cholesterol， and high sensitivity C-reactive protein （hs-CRP）， as well as significanty lower levels of estimated glomerular filtration rate （eGFR） and high-density lipoprotein cholesterol （all P <0.05）. Compared with the non-ASCVD group， the ASCVD group had significantly higher levels of BMI， waist circumference， SBP， DBP， UA， FBG， TG， and hs-CRP and a significantly lower level of eGFR （all P<0.05）. The incidence rate of new-onset ASCVD continued to increase over time in the MAFLD group and the non-MAFLD group， while the incidence rate of new-onset MAFLD firstly increased and then remained stable over time in the ASCVD group and the non-ASCVD group. There were 4 263 cases （14.70%） of new-osnet ASCVD in the MAFLD group， with an incidence density of 12.90 per 1 000 person-years， while there were 6 529 cases （9.66%） of new-osnet ASCVD in the non-MAFLD group， with an incidence density of 8.24 per 1 000 person-years， and there were significant differences in the incidence density and cumulative incidence rate of ASCVD between the two groups （χ²=519.09 and 531.80， both P<0.05）. There were 148 cases （30.77%） of new-onset MAFLD in the ASCVD group， with an incidence density of 40.10 per 1 000 person-years， while there were 32 194 cases （46.56%） of new-onset MAFLD in the non-ASCVD group， with an incidence density of 57.59 per 1 000 person-years， and there were significant differences in the incidence density and cumulative incidence rate of MAFLD between the two groups （χ²=19.29 and 30.78， both P<0.05）. The corrected multivariate Cox proportional-hazards regression model analysis showed that MAFLD was a risk factor for new-onset ASCVD （hazard ratio ［HR］=1.11， 95% confidence interval ［CI］： 1.06 — 1.16， P<0.001）， while ASCVD was a protective factor against new-onset MAFLD （HR=0.72， 95%CI： 0.61 — 0.85， P<0.001）. ConclusionThere is a significant association between MAFLD and ASCVD， with an increase in the risk of ASCVD in the MAFLD population and a reduction in the risk of MAFLD in the ASCVD population.

[摘 要] 目的：探讨年轻乳腺癌独特的DNA甲基化特征，筛选与预后相关的甲基化位点，构建并验证预后预测模型，并通过多组学整合及关键蛋白验证评估其临床价值。方法：收集癌症基因组图谱（TCGA）数据库中的乳腺癌样本DNA甲基化及临床数据，筛选年轻乳腺癌特有的甲基化位点。采用随机森林、LASSO回归及单因素和多因素Cox比例风险回归分析构建预后模型。使用受试者工作特征（ROC）曲线、校准曲线和一致性指数（C-index）评估模型性能，并比较高、低风险组间的多组学特征差异，在独立队列中通过免疫组化法检测模型关键基因LAMA5的蛋白表达，分析其与预后的关系。结果：年轻乳腺癌相较于老年乳腺癌，在启动子区域（尤其是CpG岛）呈现显著低甲基化特征。通过多步骤差异分析获得3 489个年轻乳腺癌特有的甲基化位点，经Cox比例风险回归筛选出12个与总生存期（OS）独立相关的位点，其中启动子区、基因体区和基因间区位点各4个。基于筛选出的12个甲基化位点构建的预测模型，在TCGA训练集中显示出良好的区分度，高风险组总生存期显著更差（P = 0.002 5），5、8和10年OS预测曲线下面积（AUC）达0.88～0.94。多组学分析显示，高风险组丝裂原活化蛋白激酶（MAPK）信号通路激活，TP53基因突变频率更高，雌激素受体α蛋白表达较低。将TP53突变状态及雌激素受体1（ESR1）mRNA表达水平等关键多组学指标纳入模型，构建综合列线图，其预测效能进一步提升。组织芯片验证显示，模型关键基因LAMA5蛋白表达阴性患者的OS更差（P = 0.046），且富集于三阴性乳腺癌，与模型高风险组的临床病理特征一致。结论：整合启动子和非启动子区域信息的基于12个甲基化位点的模型可用于年轻乳腺癌患者的预后分层。联合年龄、TP53突变及ESR1 mRNA表达水平构建的综合列线图显示出较单一甲基化模型更高的预测效能。

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Objective:To evaluate the effects of different volumes of ropivacaine for iliopsoas muscle plane block on quadriceps strength in patients undergoing hip arthroplasty.Methods:In this prospective study, 75 patients of either sex, aged 40-80 yr, with a body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing elective hip arthroplasty from June to December 2023 at Baoding First Central Hospital, were randomized into 3 groups ( n=25 each) by using a computer-generated randomization sequence: ropivacaine 5 ml group (group Ⅰ), ropivacaine 10 ml group (group Ⅱ), and ropivacaine 15 ml group (group Ⅲ). Before induction of anesthesia, iliopsoas muscle plane block was performed with 0.5% ropivacaine 5, 10 and 15 ml in Ⅰ, Ⅱ and Ⅲ groups, respectively. The lateral femoral cutaneous nerve block was carried out using 0.5% ropivacaine 5 ml in all the three groups. The quadriceps muscle strength and status of quadriceps motor block in the affected limb were assessed on admission to postanesthesia care unit (PACU) and at 2, 4, 6, 24 and 48 h after surgery. The consumption of dezocine, score for patient′s satisfaction with analgesia, and occurrence of complications were recorded. Results:Compared with group Ⅰ, the quadriceps muscle strength scores were significantly decreased on admission to PACU and at 2, 4 and 6 h postoperatively in group Ⅲ, the rate of quadriceps motor block was significantly increased on admission to PACU in group Ⅱ, and the rate of quadriceps motor block was significantly increased on admission to PACU and at 2 and 4 h postoperatively in group Ⅲ ( P<0.05), and the consumption of dezocine was significantly decreased in group Ⅱ and group Ⅲ ( P<0.05). Conclusions:The recommended volume of ropivacaine for iliopsoas plane block is 10 ml in patients undergoing hip arthroplasty.

Objective:To analyze the effect of continuous positive airway pressure (CPAP) on maternal and neonatal outcomes in pregnant women with obstructive sleep apnea syndrome (OSAS), especially on the incidence of hypertensive disorder in pregnancy (HDP) in women with moderate to severe OSAS.Methods:A total of 180 pregnant women with OSAS who were diagnosed through sleep monitoring during pregnancy due to high-risk factors of OSAS and registered in Peking University People′s Hospital from January 2021 to May 2024 were selected as the study subjects. Clinical data were collected from medical records for retrospective analysis. According to whether they received standardized treatment with CPAP, they were divided into the CPAP treatment group (42 cases) and the control group (138 cases). The CPAP treatment group consisted of 9 pregnant women with moderate to severe OSAS, while the control group consisted of 34 pregnant women with moderate to severe OSAS. The maternal and neonatal outcomes, the incidence of HDP, placental weight after delivery and placental weight/neonatal birth weight ratio were compared between the two groups.Results:(1) The average gestational age of pregnant women in the CPAP treatment group was higher than that in the control group [(38.7±1.0) vs (38.0±1.4) weeks], the proportion of infants small for gestational age (SGA) in the CPAP treatment group was lower [0 (0/42) vs 12.3% (17/138)], and the birth weight of infants in the CPAP treatment group was bigger [(3 396±475) vs (3 082±710) g); the differences between the two groups were statistically significant (all P<0.05). There were no significant differences between the CPAP treatment group and the control group in terms of delivery mode, rates of postpartum hemorrhage and preterm birth, umbilical artery blood gas analysis pH<7.1, lactate≥6.0 mmol/L, base excess<-12.0 mmol/L and the incidence of gestational diabetes mellitus and HDP (all P>0.05). (2) The placental weight of the CPAP treatment group was significantly lower than that of the control group [(554.0±70.6) vs (615.7±119.1) g], the placental weight/newborn birth weight ratio of the CPAP treatment group was significantly lower than that of the control group (median: 0.17 vs 0.19), and the differences were statistically significant (all P<0.05). (3) The incidence of HDP in pregnant women with moderate to severe OSAS in the CPAP treatment group was lower than that in the control group [1/9 vs 61.8% (21/34)], and the difference was statistically significant ( P<0.05). Conclusions:CPAP treatment could prolong the gestational age in pregnant women with OSAS, reduce the incidence of SGA, increase the birth weight of infants, and reduce the incidence of HDP in pregnant women with moderate to severe OSAS, and is worth promoting in clinical practice. The improvement of neonatal outcomes by CPAP treatment is closely related to the placenta, which is worthy of further exploration.

Objective:Effects of Qingsui Xiaoyan Decoction on osteoclast differentiation of RAW264.7 cells.Methods:Receptor activator of nuclear factor kappa B ligand (RANKL) was used to induce differentiation of RAW264.7 cells into osteoclasts. CCK-8 method was used to screen experimental drug concentrations and analyze the cytotoxicity of drug intervention on RAW264.7 cells. TRAP staining method was used to quantitatively detect the effects of Qingsui Xiaoyan Decoction on osteoclast differentiation ability. RT-PCR technology was used to detect the mRNA expressions of osteoclast differentiation genes TRAP, MMP-9, CK, CTR. Western blot was used to detect osteoclast-related protein expressions of NF-κBP65, IκB-αTRAP, and TRAP.Results:After 72 hours of intervention, 0.800, 4.000, 20.000, and 100.000 mg/ml of Qingsui Xiaoyan Decoction could inhibit cell proliferation ( P<0.05). Compared with the model group, the number of TRAP-positive cells decreased ( P<0.05) in the 5, 20, 80, and 160 μg/ml Qingsui Xiaoyan Decoction groups. Additionally, the mRNA levels of TRAP, MMP-9, CK, and CTR decreased ( P<0.05), the expression of NF-κB p65 and TRAP proteins decreased ( P<0.05), and the expression of IκB-α protein increased ( P<0.05). Conclusions:Qingsui Xiaoyan Decoction can inhibit the expressions of TRAP, MMP-9, CK, CTR genes and TRAP protein, reduce the degradation of I κ B - α protein by inhibiting the NF - κ B signaling pathway, inhibit the expression of NF - κ B p65 protein, and thus inhibit the differentiation of RAW264.7 into osteoclasts.

Reactive oxygen species (ROS) are major contributors to radiation therapy-induced side effects in cancer patients. A fusion antioxidant enzyme comprising glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and a transmembrane peptide has been shown to effectively mitigate ROS-induced damage. To enhance its targeting capability, the fusion protein was further modified by incorporating a matrix metalloproteinase-2/9 substrate peptide (X) and the transmembrane peptide R9, yielding the antioxidant enzyme GST-SOD1-X-R9 (GS1XR). This modification reduced its transmembrane ability in tumor cells, thereby selectively protecting normal cells from oxidative stress. However, the use of non-human GST poses potential immunogenicity risks. In this study, we employed seamless cloning technology to construct an expression vector containing the human GST gene to replace the non-human GST gene, and then expressed and purified novel fusion antioxidant enzymes GS1R and GS1XR. The protective effects of newly constructed GS1R and GS1XR against hydrogen peroxide (H₂O₂)-induced oxidative damage in L-02 cells were then evaluated using GS1 as a control. Enzymatic activity assays revealed that the specific activity of GST in GS1XR remained unchanged compared to the unmodified protein, while SOD activity was enhanced. Exposure to 200 μmol/L H₂O₂ transiently activated the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway; however, this activation diminished after 24 h, reducing cell viability to 48.4%. Both GS1R and GS1XR effectively scavenged intracellular ROS, directly counteracting oxidative stress and promoting Nrf2 nuclear translocation, thereby activating antioxidant pathways and restoring cell viability to normal levels. The two enzymes showed comparable efficacy. In contrast, GS1, lacking transmembrane capability, was restricted to scavenging extracellular ROS and provided only limited protection. In conclusion, both novel fusion antioxidant enzymes demonstrated significant potential in safeguarding normal cells from ROS-mediated oxidative damage. The findings provide a foundation for further investigation in related field.
Humans ; Oxidative Stress/drug effects* ; Hydrogen Peroxide ; Antioxidants/metabolism* ; Glutathione Transferase/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; Superoxide Dismutase-1 ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/biosynthesis*

This study was aimed at investigating the prevalence of Dabie bandavirus(DBV)infection in suspected cases of se-vere fever with thrombocytopenia syndrome(SFTS)and tick specimens in Cangzhou City from 2023 to 2024,and providing scientific basis for the prevention,control and pathogen surveillance of SFTS in this area.Pathogen detection and virus isolation were performed on suspected SFTS cases and tick specimens collected in Cangzhou City from 2023 to 2024.The next-generation sequencing technol-ogy was used to conduct whole-genome sequencing of DBV.A phylogenetic tree was constructed using software such as MEGA,DNA Star,and homology comparison and amino acid variation site analysis were carried out.Among the 70 suspected SFTS cases,the DBV positive detection rate was 60%(42/70).The positive cases were mainly farmers aged 50-79,concentrated in Yanshan County and Haixing County.402 ticks were pooled into 31 sample tubes,among which 2 tubes tested positive for DBV nucleic acid,with a mini-mum infection rate of 0.50%.A total of 9 human-derived and 2 tick-derived DBV strains were isolated.The whole-genome sequencing results showed that all strains clustered within the F branch,with sequences homology exceeding 99%.There were a total of 10 amino acid variation sites in the RdRP,GP and NSs sequences.Therefore,the distribution of SFTS cases in Cangzhou City exhibited regional clustering.The overall level of DBV infection in ticks in this region was relatively low.It is recommended to further improve the disease early warning mechanism and continue to conduct pathogen surveillance.

Objective:To evaluate the effect of smoking on the sedative potency of remimazolam combined with alfentanil in patients undergoing painless gastroscopy.Methods:This was a prospecctive single-center study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ male patients, aged 30-75 yr, with a body mass index of 18-28 kg/m 2, undergoing elective painless gastroscopy at Baoding First Central Hospital from October to December 2023, were divided into non-smoking group, mild smoking group (smoking index≤200), moderate smoking group (200 1 after 3 min of remimazolam injection or development of bucking, swallowing, body movement and other responses that affected operations during insertion of the endoscope. Results:A total of 85 patients were finally included, with 21 in non-smoking group, 21 in mild smoking group, 20 in moderate smoking group and 23 in heavy smoking group. The ED 50 of remimazolam was significantly higher in smoking groups than in non-smoking group ( P<0.05). The ED 50 of remimazolam gradually increased in mild, moderate and heavy smoking groups ( P<0.05). Conclusions:Smoking can decrease the sedative potency of remimazolam when combined with alfentanil in patients undergoing painless gastroscopy.