ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To investigate the midterm and long-term efficacy of flow-diverter device in treating intracranial aneurysms (IAs) and analyze its clinical outcomes in anterior circulation aneurysms and posterior circulation aneurysms.Methods:This is a retrospective case series study. The data of 566 intracranial aneurysm patients (681 aneurysms) treated with the flow-diverter device at Department of Neurosurgery, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University from January 2018 to January 2021 were retrospectively analyzed. There were 205 males and 361 females, with an age ( M(IQR)) of 55 (14) years (range:18 to 77 years). Twelve patients (12 aneurysms) had ruptured aneurysms before surgery, and 75 patients (172 aneurysms) had multiple aneurysms. Preoperative modified Rankin scale (mRS) >2 points in 16 patients.There were 444 patients (552 aneurysms) in the anterior circulation group and 122 patients (129 aneurysms) in the posterior circulation group. Postoperative follow-up was conducted via outpatient visits or telephone calls at 3 to 12 months after the procedure. Baseline aneurysm parameters, surgical information, and imaging and clinical outcomes were collected. Univariate and multivariate Logistic regression analyses were used to identify independent factors associated with long-term incomplete aneurysm occlusion. Results:Intraoperative use of flow diverter-assisted coil embolization was performed in 221 patients (226 aneurysms), and balloon assistance was used in 20 patients (22 aneurysms).The intraoperative rupture rate was 0.5% (3/566), and the intraoperative thrombosis rate was 0.7% (4/566). The in-hospital mortality rate was 1.2% (7/566). Postoperative complications included subarachnoid hemorrhage in 5 patients (0.9%), intracerebral hemorrhage in 2 patients (0.4%), ischemic stroke in 19 patients (3.6%), and transient ischemic attack in 16 patients (3.0%). Imaging follow-up was available for 447 patients (548 aneurysms) with a follow-up duration of (16.7±6.7) months (range:3 to 45 months). Incomplete aneurysm occlusion occurred in 79 patients (95 aneurysms), accounting for 17.3% (95/548). Parent artery stenosis was observed in 63 patients (72 aneurysms), accounting for 13.1% (72/548). Clinical follow-up was available for 530 patients (644 aneurysms) with a follow-up duration of (29.4±11.3) months (range:3 to 54 months). One case of mRS score >2 points was observed in 18 patients, accounting for 3.4% (18/530). Among them, the rate of incomplete occlusion in the anterior and posterior circulation group was 16.9% (76/450) and 19.4% (19/98), respectively, and the rate of parent artery stenosis was 10.9% (49/450) and 23.5% (23/98), respectively; the rate of mRS score>2 points was 2.4% (10/415) and 7.0% (8/115), respectively. Univariate and multivariate Logistic regression analysis showed that aneurysm neck size ( β=0.075, OR=1.08, P=0.028) and coil use ( β=-1.070, OR=0.034, P=0.001) were independent factors influencing long-term aneurysm occlusion. Conclusions:The flow-diverter device demonstrates good safety and efficacy in the midterm and long-term treatment of overall IAs. However, further research is needed to focus on the midterm and long-term treatment outcomes of aneurysms with relatively wide neck and posterior circulation aneurysms.

Objective The reliability and validity of the SGGC-Net-based motion capture system(SGGC-Net system)and SIMI system for parsing walking gait were compared using a three-dimensional(3D)motion capture system(Vicon)with marker points as a reference standard.Methods Thirty healthy college students were recruited,and their gait characteristics while walking on a treadmill were analyzed.Kinematic data were collected using the Vicon system,and video data were collected synchronously using four cameras to obtain the right shoulder,elbow,hip,knee,and ankle joint angles.Reliability was assessed using intraclass correlation coefficients(ICCs)with 95％confidence intervals and standard error of measurement(SEM).Validity was assessed using multiple correlation coefficients(MCCs)and root mean square errors(RMSEs).Results The ICCs of the maximum and minimum 3D coordinate angles of the upper and lower limb joints of the SGGC-Net system ranged from 0.798-0.990 with an SEM of 0.04°-0.95°,and the ICCs of the SIMI system ranged from 0.650-0.967,with an SEM of 0.31°-1.24°.The ICCs of the SGGC-Net system were higher than those of the SIMI system for all joint angles except for the minimum hip and maximum knee angles.Compared to the joint angle curves derived from the SIMI system,the MCCs of the curves derived from the SGGC-Net system ranged from 0.945-0.996,with RMSEs of 1.44°-4.65°,and the multiple correlation coefficients of the SIMI system ranged from 0.815-0.986,with RMSEs of 2.56°-9.99°.The MCCs of the SGGC-Net system were greater than those of the SIMI system at all angles except for the ankle joint.The RMSEs of the SGGC-Net system were smaller than those of the SIMI system at all angles except for the ankle joints.Conclusions The SGGC-Net system has better reliability and validity than the SIMI system in most of the variables,and it has better repeatability and accuracy in analyzing walking gait.It can be applied to motion capture environments without marker points,such as technical analysis of athletes'movements and clinical gait analysis of special populations.

Objective:To investigate the midterm and long-term efficacy of flow-diverter device in treating intracranial aneurysms (IAs) and analyze its clinical outcomes in anterior circulation aneurysms and posterior circulation aneurysms.Methods:This is a retrospective case series study. The data of 566 intracranial aneurysm patients (681 aneurysms) treated with the flow-diverter device at Department of Neurosurgery, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University from January 2018 to January 2021 were retrospectively analyzed. There were 205 males and 361 females, with an age ( M(IQR)) of 55 (14) years (range:18 to 77 years). Twelve patients (12 aneurysms) had ruptured aneurysms before surgery, and 75 patients (172 aneurysms) had multiple aneurysms. Preoperative modified Rankin scale (mRS) >2 points in 16 patients.There were 444 patients (552 aneurysms) in the anterior circulation group and 122 patients (129 aneurysms) in the posterior circulation group. Postoperative follow-up was conducted via outpatient visits or telephone calls at 3 to 12 months after the procedure. Baseline aneurysm parameters, surgical information, and imaging and clinical outcomes were collected. Univariate and multivariate Logistic regression analyses were used to identify independent factors associated with long-term incomplete aneurysm occlusion. Results:Intraoperative use of flow diverter-assisted coil embolization was performed in 221 patients (226 aneurysms), and balloon assistance was used in 20 patients (22 aneurysms).The intraoperative rupture rate was 0.5% (3/566), and the intraoperative thrombosis rate was 0.7% (4/566). The in-hospital mortality rate was 1.2% (7/566). Postoperative complications included subarachnoid hemorrhage in 5 patients (0.9%), intracerebral hemorrhage in 2 patients (0.4%), ischemic stroke in 19 patients (3.6%), and transient ischemic attack in 16 patients (3.0%). Imaging follow-up was available for 447 patients (548 aneurysms) with a follow-up duration of (16.7±6.7) months (range:3 to 45 months). Incomplete aneurysm occlusion occurred in 79 patients (95 aneurysms), accounting for 17.3% (95/548). Parent artery stenosis was observed in 63 patients (72 aneurysms), accounting for 13.1% (72/548). Clinical follow-up was available for 530 patients (644 aneurysms) with a follow-up duration of (29.4±11.3) months (range:3 to 54 months). One case of mRS score >2 points was observed in 18 patients, accounting for 3.4% (18/530). Among them, the rate of incomplete occlusion in the anterior and posterior circulation group was 16.9% (76/450) and 19.4% (19/98), respectively, and the rate of parent artery stenosis was 10.9% (49/450) and 23.5% (23/98), respectively; the rate of mRS score>2 points was 2.4% (10/415) and 7.0% (8/115), respectively. Univariate and multivariate Logistic regression analysis showed that aneurysm neck size ( β=0.075, OR=1.08, P=0.028) and coil use ( β=-1.070, OR=0.034, P=0.001) were independent factors influencing long-term aneurysm occlusion. Conclusions:The flow-diverter device demonstrates good safety and efficacy in the midterm and long-term treatment of overall IAs. However, further research is needed to focus on the midterm and long-term treatment outcomes of aneurysms with relatively wide neck and posterior circulation aneurysms.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective:To investigate the biological effects of acute high-dose radon exposure on mice.Methods:BALB/c male mice aged 6 to 8 weeks were exposed once in an HD-3 ecological radon chamber with an average radon concentration of 7 × 10 5 Bq/m 3 for 10 h. Mice were weighed, their lung tissues and blood samples were collected at 1, 2 and 3 months after exposure. Control groups were set up at the three time points with four mice in each group. For these mice, the lung tissue pathology was observed using hematoxylin-eosin (HE) staining method, routine blood tests were conducted using a hematology analyzer and the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the serum and lung tissues were measured using corresponding assay kits. Results:The HE staining result revealed that compared to the control groups, the experimental groups exhibited thickening of alveolar walls and increased infiltration of granulocyte, whose degrees, however, reduced over time and displayed no significant difference at 3 months after exposure. There was no significant difference in body weight or blood routine between the experimental and control groups. The detection result revealed decreased SOD levels in the lung tissues at 2 months after exposure, which were (11.34 ± 1.03) U/mgprot and (9.75 ± 0.71) U/mgprot, respectively for the control and experimental groups ( t = 2.54, P < 0.05). The MDA levels in lung tissue increased at 1 month after exposure, which were(2.30 ± 0.24) and (2.77 ± 0.29) nmol/mgprot, respectively for the control and experimental groups ( t = 2.49, P < 0.05). At 3 months after exposure, the SOD and MDA levels differed insignificantly between the control and experimental groups ( P > 0.05). Conclusions:After acute high-dose radon exposure, the mice suffered damage to the lung tissue, with changes in their oxidative stress indicators being detected. However, these effects gradually diminished at 3 months after exposure. Additionally, acute high-dose radon exposure did not give rise to significant changes in the body weight or routine blood result of the mice.

Nonalcoholic fatty liver disease （NAFLD） is one of the most common complications of type 2 diabetes mellitus （T2DM）. Cell death caused by iron-lipid disorder is a new mode of regulating programmed cell death， which is characterized by lipid peroxidation induced by the accumulation of lipid reactive oxygen species and excessive accumulation of iron ions induced by iron metabolism disorders. Among them， iron homeostasis disorder and metabolic pathway disorder are the main causes of iron-lipid disorder， which play an important role in a variety of pathological processes related to cell death. Because the liver is an important organ for iron storage and lipid metabolism， iron-lipid disorder is an ideal target for liver disease， and inhibition of iron-lipid disorder may become a new strategy for the treatment of NAFLD. However， the pathogenic relationship and mechanism between NAFLD and iron-lipid disorder have not been fully elucidated. Based on the complex molecular regulation mechanism of iron-lipid disorder， by expounding the role of iron-lipid disorder in NAFLD and its related mechanism， this paper summarizes the research status of traditional Chinese medicine on the target treatment of NAFLD in recent years， so as to provide a new perspective and point out a new direction for the treatment of NAFLD in the future.