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.

Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

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 role of inositol 1, 4, 5 triphosphate receptor 1 (IP3R1)-regulated changes in mitochondria-associated endoplasmic reticulum membrane (MAM) structure in the long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal mice.Methods:Sixty SPF-grade healthy neonatal C57BL/6J mice of either sex, aged 6 days, weighing 6-10 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), multiple sevoflurane anesthesia group (group S), and IP3R antagonist 2-APB+ multiple sevoflurane anesthesia group (group I+ S). Group S and group I+ S inhaled 3% sevoflurane anesthesia for 2 h starting from 6, 8 and 10 days after birth. In group I+ S, 2-APB 3 mg/kg was intraperitoneally injected before each sevoflurane anesthesia. The open field test was performed at day 31 after birth to assess the spontaneous mobility. The Morris water maze test was performed at days 31-36 after birth to assess the cognitive function. Mice were sacrificed at the end of the water maze test, hippocampal CA1 region was isolated and hippocampal tissues were obtained for determination of the intracellular calcium ion concentration ([Ca 2+ ] i) and rate of necroptosis (using Flow cytometry) and expression of IP3R1, G protein-coupled receptor 75 (GRP75), receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated human mixed-series protein kinase-like structural domains (p-MLKL) (by Western blot). Transmission electron microscopy was performed to observe and record the partial length of MAMs, endoplasmic reticulum circumference and mitochondrial circumference. Results:There were no statistically significant differences in the speed, distance, and time of staying at the center in open field tests among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged on postnatal days 33-35, the number of crossing the original platform was reduced, the necroptosis rate in the hippocampal CA1 region and [Ca 2+ ] i were increased, the expression of IP3R, GRP75, RIPK1, RIPK3 and p-MLKL was up-regulated, and the ratio of MAMs partial length/endoplasmic reticulum perimeter and ratio of MAMs partial length/mitochondria perimeter in hippocampal neurons were elevated in group S ( P<0.05). Compared with group S, the escape latency was significantly shortened on postnatal days 32-35, the number of crossing the original platform was increased, the necroptosis rate in the hippocampal CA1 region and [Ca 2+ ] i were decreased, the expression of IP3R, GRP75, RIPK1, RIPK3 and p-MLKL was down-regulated, and the ratio of MAMs partial length/endoplasmic reticulum perimeter and ratio of MAMs partial length/mitochondria perimeter in hippocampal neurons were decreased in group I+ S ( P<0.05). Conclusions:Structural changes in MAMs in the hippocampal CA1 region mediated by the up-regulation of IP3R1 expression are involved in the process of long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal mice.

Objective:To evaluate the relationship between sevoflurane preconditioning-induced reduction of cognitive impairment and hippocampal necroptosis after cardiopulmonary bypass (CPB) in rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 6 months, weighing 400-450 g, were divided into 4 groups ( n=15 each) using the random number table method: control group (group C), sevoflurane group (Sev group), CPB group and CPB+ sevoflurane preconditioning group (CPB+ Sev group). The rats were exposed to 0.4% sevoflurane for 2 h in CPB+ Sev group and Sev group. The CPB model was established at 30 min after the end of sevoflurane preconditioning in CPB+ Sev group. The open field test was performed to assess the autonomic movement ability on the 2nd day after CPB. The Morris water maze test was used to assess the cognitive function on the 3rd day after CPB. The hippocampal tissues were removed after the end of the Morris water maze test for determination of the necroptosis rate and cytosolic calcium concentration of hippocampal neuron ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated receptor-interacting protein kinase 1 (p-RIPK1), phosphorylated RIPK3 and phosphorylated mixed-lineage kinase-like domain (p-MLKL) (by Western blot) and for microscopic examination of the ultrastructure of hippocampal neurons (by transmission electron microscopy). Results:There was no statistically significant difference in the parameters of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, the time of staying at the original platform quadrant was shortened, the hippocampal necroptosis rate and [Ca 2+ ] i were increased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was up-regulated ( P<0.05), the organelles of hippocampal neurons swelled, lysosomes broke, and some chromatin in nuclei dissoluted in CPB group. Compared with CPB group, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, the hippocampal necroptosis rate and [Ca 2+ ] i were decreased, the expression of p-RIPK1, p-RIPK3 and p-MLKL was down-regulated ( P<0.05), and the damage to the ultrastructure of hippocampal neurons was sinificantly reduced in CPB+ Sev group ( P<0.05). Conclusions:The mechanism by which sevoflurane preconditioning attenuates cognitive impairment may be related to the inhibition of calcium overload-mediated hippocampal necroptosis in a rat model of CPB.

Objective:To evaluate the role of RhoA/ROCK2 pathway in electroacupuncture (EA) preconditioning-induced reduction of the perioperative neurocognitive disorder (PND) in aged rats.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using the random number table method: sham operation group (group S), PND group, EA preconditioning group and EA preconditioning plus RhoA agonist arachidonic acid group (EA+ AA group). The PND model was prepared using exploratory laparotomy performed under 3% sevoflurane anesthesia. In PND, EA and EA+ AA groups, EA preconditioning was initiated 5 days before operation as follows: Bilateral acupoints Zusanli, Hegu and Neiguan were stimulated with sparse-dense waves at 2/15 Hz and an electric current intensity of 1 mA, applied for 30 min a day for 5 consecutive days. Arachidonic acidin 10 mg/kg was intraperitoneally injected at 30 min before surgery in group AA. The open field test was conducted at 3 days postoperatively to measure the autonomous motor function, and the Morris water maze test was conducted at 3-7 days postoperatively to evaluate the cognitive function. After the end of Morris water maze test, the rats were sacrificed, and the hippocampal tissue in CA1 region was obtained for determination of the apoptosis rate of cells and concentrations of cytoplasmic calcium ion ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated RhoA (p-RhoA), ROCK2, and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:There was no statistically significant difference in each parameter of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was marked in PND group. Compared with PND group, the escape latency was significantly shortened, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was significantly attenuated in EA group. Compared with EA group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was aggravated in EA+ AA group. Conclusions:The mechanism by which EA preconditioning reduces PND is related to inhibiting the activation of hippocampal RhoA/ROCK2 signaling pathway and reducing calcium overload-mediated apoptosis in cells of aged rats.

Objective:To evaluate the relationship between superoxide dismutase 2 (SOD2) lactylation and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy-ferroptosis during cerebral ischemia-reperfusion (IR) in mice.Methods:Thirty-six clean-grade male C57BL/6 mice, aged 8-10 weeks, weighing 22-25 g, were divided into 4 groups ( n=9 each) using a table of random numbers: sham operation group (Sham group), cerebral IR group (IR group), IR+ glycolysis inhibitor 2-DG group (IR+ 2-DG group), and IR+ 2-DG+ NCOA4 overexpression group (IR+ 2-DG+ LvNCOA4 group). The model of cerebral IR injury was established by occlusion of the middle cerebral artery for 1 h followed by 24 h of reperfusion using the intraluminal suture method in anesthetized animals. 2-DG 250 mg/kg was intraperitoneally injected at 90 min before ischemia in IR+ 2-DG and IR+ 2-DG+ LvNCOA4 groups. The lentivirus overexpressing NCOA4 2 μl was injected into the ventricles at 7 days before ischemia in IR+ 2-DG+ LvNCOA4 group. The percentage of cerebral infarct volume was determined, the viable neurons were counted, and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) were measured by enzyme-linked immunosorbent assay. The expression of SOD2, lysine 114 lactylation of superoxide dismutase 2 (SOD2-K114la), NCOA4, microtubule-associated protein 1 light chain 3β (LC3B), and acyl-CoA synthetase long-chain family member 4 (ACSL4) was determined by Western blot. Mitochondrial morphology was examined by electron microscopy. Results:Compared with Sham group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, the expression of SOD2-K114la, NCOA4, LC3B and ACSL4 was up-regulated, the expression of SOD2 was down-regulated ( P<0.05), and the mitochondrial injury was aggravated in IR group. Compared with IR group, the percentage of cerebral infarct volume was significantly decreased, the number of viable neurons was increased, the mitochondrial injury was alleviated, the levels of ROS and MDA were decreased, the content of GSH was increased, the expression of SOD2-K114la, NCOA4 and ACSL4 was down-regulated, and the expression of SOD2 and LC3B was up-regulated in IR+ 2-DG group ( P<0.05). Compared with IR+ 2-DG group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, and the expression of NCOA4, LC3B and ACSL4 was up-regulated ( P<0.05), no significant change was found in the expression of SOD2 and SOD2-K114la ( P>0.05), and the mitochondrial injury was aggravated in IR+ 2-DG+ LvNCOA4 group. Conclusions:SOD2 lactylation promotes NCOA4-mediated ferritinophagy-ferroptosis by enhancing oxidative stress, thereby contributing to the cerebral IR injury in mice.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Objective:To predict the monthly incidence of hemorrhagic fever with renal syndrome (HFRS) in Hebei Province by using the generalized additive model (GAM).Methods:The incidence data of HFRS in Hebei from 2006 to 2020 were collected, and the correlation coefficients between meteorological factors and the monthly incidence of HFRS in Hebei were analyzed by Spearman's correlation, and the meteorological factors were lagged by 0-6 orders, and those with the largest absolute values of the correlation coefficients were screened to be included in the multifactorial GAM to evaluate the effects of meteorological factors.Results:The monthly incidence of HFRS had the strongest correlation with monthly mean air temperature at lag order 2, monthly mean wind speed at lag order 0, monthly mean sunshine at lag order 4, monthly mean precipitation at lag order 2 and monthly mean humidity at lag order 1, which were diagnosed by the variance inflation factor and included in the multifactorial GAM, and the results showed significant differences among the factors (all P<0.001), and they showed non-linear relationships with the monthly incidence of HFRS. Mean monthly temperature was an important factor influencing HFRS incidence. Mean monthly air temperature, mean monthly sunshine and mean monthly wind speed were negatively associated with HFRS incidence, whereas mean monthly precipitation and mean monthly humidity were positively associated with HFRS incidence. Conclusions:There was a complex non-linear relationship between meteorological factors and the incidence of HFRS. GAM incorporated with lagged meteorological factors can be used to predict the incidence of HFRS in Hebei.