Liver fibrosis is caused by various factors such as viral infection， alcohol intake， and metabolism-related damage， leading to the replacement of normal tissue by fibrous scars. As a regulatory factor for cell proliferation， insulin-like growth factor 1 （IGF-1） participates in the regulation of cell cycle， the promotion of cell proliferation and differentiation， and the inhibition of cell apoptosis by binding to its receptor insulin-like growth factor-1 receptor （IGF-1R）. Studies have shown that the IGF-1/IGF-1R signaling pathway can regulate the process of liver fibrosis by affecting the senescence and apoptosis of hepatocytes， the activation and proliferation of hepatic stellate cells， and the dysfunction of endothelial cells. In addition， the IGF-1/IGF-1R signaling system can also regulate multiple mechanisms such as DNA damage repair， cell proliferation， lipid metabolism， cell senescence， and oxidative stress， thereby providing new strategies and potential targets for the prevention and treatment of liver fibrosis. This article summarizes the mechanism of action of IGF-1/IGF-1R and its signal transduction system in mediating liver fibrosis by regulating DNA damage repair in different cells， in order to provide a theoretical basis for the treatment of liver fibrosis.

The interstitial cells of Cajal (ICC) generate spontaneous pacemaker activities responsible for producing slow waves in the gut smooth muscles. Prostaglandin E2 (PGE2 ) is one of the most important prostanoids in the gut, playing a crucial role in multiple physiological and pathological processes. Because information regarding the effects of PGE2 on colonic ICC is limited, we investigated the effects of PGE2 and its underlying signaling pathways in murine colonic ICC. Whole-cell patch-clamp recordings and reverse transcription polymerase chain reaction (RT-PCR) analyses were performed to evaluate the effects of PGE2 on mouse colonic ICC. PGE2 had a dual effect on pacemaker potential in the current-clamp mode. RT-PCR data suggested the expression of EP3 and EP4 receptors in colonic ICC. Low PGE2 concentrations induced membrane depolarization and generation of pacemaker activities. And this effect is mimicked by sulprostone (an EP3 agonist). The low PGE2 concentration-induced effect was inhibited by anoctamin-1 (ANO1) or a T-type Ca2+ channel blocker. Conversely, high PGE2 concentrations induced membrane hyperpolarization and blocked pacemaker potential generation. However, this inhibitory effect was blocked by an ATP-sensitive potassium (K ATP) channel blocker but not by other K+ channel blockers. Low concentrations of PGE2 activated EP3 receptors, leading to excitation of pacemaker activity through regulation of ANO1 and T-type Ca2+ channels in colonic ICC. In contrast, higher concentrations of PGE2 activated EP4 receptors and opened ATP-sensitive K+ channels, resulting in inhibition of pacemaker activity in colonic ICC.

Metabolic associated fatty liver disease （MAFLD） is a highly prevalent chronic liver disease worldwide， and the mechanism underlying its progression to metabolic associated steatohepatitis and liver fibrosis remain unclear. Endoplasmic reticulum stress （ERS） and ferroptosis （Fer） are deeply involved in the pathological evolution of MAFLD. This article systematically reviews the core regulatory mechanisms of ERS and its role in regulating lipid metabolism， inflammation response， and cell apoptosis in MAFLD. It also analyzes the core mechanism of Fer and discusses the predisposing factors for Fer in the pathological microenvironment of MAFLD， as well as the role of Fer in exacerbating hepatocyte death and activating the progression of liver fibrosis. This article proposes that the crosstalk between ERS and Fer is a key driver for the progression of MAFLD， which provides new references and ideas for the clinical intervention of MAFLD.

ObjectiveTo study the chemical constituents of Bidens pilosa and the in vitro antiproliferative activity of some compounds against gastric cancer cells. MethodsThe chemical constituents were isolated and purified by methods such as silica gel column chromatography， preparative thin layer chromatography， medium pressure preparation chromatography， semi-preparative high performance liquid chromatography（HPLC） and recrystallization， their structures were identified on the basis of physicochemical properties， spectral data and circular dichroism spectra. Thiazole blue（MTT） assay was used to determine the in vitro inhibitory activityies of some isolated compounds against human gastric cancer SGC-7901 cells， and molecular docking was used to predict their potential targets. ResultsTwenty-five compounds were isolated from the petroleum ether fraction of B. pilosa and identified as bidpillignan A（1）， 5α， 8α-epidioxy-（22E， 24R）-ergosta-6， 22-diene-3β-ol（2）， 3β-hydroxysitost-5-en-7-one（3）， （20R）-6β-hydroxystigmasta-4， 22-dien-3-one（4）， 3β-hydroxylstigmasta-5， 22-dien-7-one（5）， （22E， 24S）-24-methyl-5α-choleata-7， 22-diene-3β， 5α， 6β-triol（6）， stigamast-5-ene-3β， 7α-diol（7）， stigmast-5， 22-diene-3β， 7α-diol（8）， 7β-hydroxysitosterol（9）， stigmasterol（10）， artabotrol（11）， cosmosoic acid（12）， ent-4（15）-eudesmene-1β， 6α-diol（13）， clovandiol（14）， 1H-indole-3-carboxaldehyde（15）， 6， 7-dimethoxycoumarin（16）， 3'， 4'-dimethoxyquercetin（17）， 8， 8'-bis-（dihydroconiferyl）-diferuloylate（18）， hydroxydihydrobovolide（19）， 2-deacetyl-11β， 13-dihydroxyxanthinin（20）， loliolide（21）， pubescone（22）， （+）-dehydrovomifoliol（23）， 2， 3-dihydroxypropyl palmitate（24） and n-hexadecane acid（25）. Among them， compound 1 was a new compound， compounds 3-9， 11-12， 18-20， 22-23 were first isolated from Bidens genus plants， and compounds 13 and 14 were isolated from this plant for the first time. Compounds 17 and 18 showed good in vitro proliferation inhibitory activities against SGC-7901 cells with the half inhibitory concentrations（IC₅₀） of 3.11， 7.22 μmol·L^-1， respectively. Molecular docking results showed that the potential targets of the two exerting anti-gastric cancer activity might be vascular endothelial growth factor receptor 2（VEGFR2） and poly（adenosine diphosphate-ribose） polymerase 7（PARP7）. ConclusionOne new compound， 14 genus first compounds， and 2 species first compounds were isolated from B. pilosa， among which compounds 17 and 18 processed anti-gastric cancer cell proliferation activity in vitro， and the targets may be VEGFR2 and PARP7.

Objective To investigate the correlation between the expression of microRNA-4319(miRNA-4319)and microRNA-4262(miRNA-4262)in early gastric carcinoma tissue and postoperative recurrence after endoscopic submucosal dissection(ESD).Methods From May 2018 to March 2020,396 patients with early gastric carcinoma who underwent ESD were regarded as the disease group,meantime,98 patients with normal gastric mucosa gastritis confirmed by pathological examination were as the control group.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)method was applied to detect the relative expression levels of miRNA-4319 and miRNA-4262 in tissues;follow up on postoperative recurrence of early gastric carcinoma patients,and the expression levels and clinical pathological characteristics of miRNA-4319 and miRNA-4262 were compared between recurrent and non recurrent patients.Multivariate Logistic regression analysis was applied to analyze the influencing factors of recurrence in early gastric carcinoma patients after ESD;receiver operating characteristic curve(ROC curve)was applied to analyze the predictive value of miRNA-4319 and miRNA-4262 in early gastric carcinoma tissue for recurrence after ESD.Results The expression levels of miRNA-4319 and miRNA-4262 in the disease group were lower than those in the control group,the differences were statistically significant(P＜0.05);The expression levels of miRNA-4319 and miRNA-4262 in the recurrence group were decreased,and the proportion of submucosal invasion was increased,the differences were statistically significant(P＜0.05).The depth of invasion to the submucosal level(OR=3.158,95％CI:1.395～7.151)was a risk factor for recurrence after ESD in patients with early gastric carcinoma(P＜0.05),and miRNA-4262 ≥ 0.76(OR=0.561,95％CI:0.370～0.852)and miRNA-4319 ≥ 0.69(OR=0.482,95％CI:0.255～0.911)were protective factors for recurrence after ESD in patients with early gastric carcinoma(P＜0.05);The area under the curve(AUC)of miRNA-4319,miRNA-4262 and their combination for predicting recurrence after ESD in patients with early gastric carcinoma was 0.889(95％CI:0.854～0.918),0.914(95％CI:0.882～0.940)and 0.964(95％CI:0.940～0.980),respectively,which was superior to the individual predictions of miRNA-4319 and miRNA-4262 respectively(P＜0.05).Conclusion MiRNA-4319 and miRNA-4262 are low expressed in tissues of early gastric carcinoma patients,they are closely related to postoperative recurrence after ESD.

OBJECTIVE To investigate the in vitro activity of Chansu injection against SARS-CoV-2 infection and determine whether bufalin is the primary active component responsible for its efficacy.METHODS The half-maximal effective concentration(EC50)of Chansu injection and bufalin against SARS-CoV-2 infection was determined using the CellTiter-Glo cell viability assay.qPCR was performed to assess the effects of Chansu injection and bufalin on mRNA levels of SARS-CoV-2 NP protein,inflammatory factors,and interferons in virus-infected cells.A cell-cell membrane fusion model was established,and the impact of the drugs on membrane fusion between HEK-293T and HEK-293T-ACE2 cells was evaluated using a luciferase reporter gene assay.RESULTS Chansu injection exhibited anti-SARS-CoV-2 virus infection activity,with an EC50 of 85.56 ng·mL-1.Chansu injec-tion significantly reduced the mRNA levels of viral NP protein(P<0.05),IFN-λ2/3(P<0.05),ISG-15 and RIG-I(P<0.000 1)in SARS-CoV-2 infected Calu-3 cells,and the mRNA levels of inflammatory factors IL-6 and TNF-α were significantly reduced(P<0.000 1).The EC50 of bufalin in inhibiting SARS-CoV-2 virus-infected cells was 13.3 nmol·L-1,which might be the main active component of Chansu injection in resisting SARS-CoV-2 virus-infected cells.Chansu injection could significantly inhibit the cell membrane fusion mediated by the S protein of SARS-CoV-2 virus,thereby blocking the virus invasion.CONCLUSION Chansu injection demonstrates in vitro anti-SARS-CoV-2 activity by suppressing NP protein expression,reducing inflammatory cytokine lev-els,and blocking viral entry through membrane fusion inhibition.Bufalin is likely the key active component responsible for its anti-SARS-CoV-2 effects.

Objective To investigate the correlation between the expression of microRNA-4319(miRNA-4319)and microRNA-4262(miRNA-4262)in early gastric carcinoma tissue and postoperative recurrence after endoscopic submucosal dissection(ESD).Methods From May 2018 to March 2020,396 patients with early gastric carcinoma who underwent ESD were regarded as the disease group,meantime,98 patients with normal gastric mucosa gastritis confirmed by pathological examination were as the control group.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)method was applied to detect the relative expression levels of miRNA-4319 and miRNA-4262 in tissues;follow up on postoperative recurrence of early gastric carcinoma patients,and the expression levels and clinical pathological characteristics of miRNA-4319 and miRNA-4262 were compared between recurrent and non recurrent patients.Multivariate Logistic regression analysis was applied to analyze the influencing factors of recurrence in early gastric carcinoma patients after ESD;receiver operating characteristic curve(ROC curve)was applied to analyze the predictive value of miRNA-4319 and miRNA-4262 in early gastric carcinoma tissue for recurrence after ESD.Results The expression levels of miRNA-4319 and miRNA-4262 in the disease group were lower than those in the control group,the differences were statistically significant(P＜0.05);The expression levels of miRNA-4319 and miRNA-4262 in the recurrence group were decreased,and the proportion of submucosal invasion was increased,the differences were statistically significant(P＜0.05).The depth of invasion to the submucosal level(OR=3.158,95％CI:1.395～7.151)was a risk factor for recurrence after ESD in patients with early gastric carcinoma(P＜0.05),and miRNA-4262 ≥ 0.76(OR=0.561,95％CI:0.370～0.852)and miRNA-4319 ≥ 0.69(OR=0.482,95％CI:0.255～0.911)were protective factors for recurrence after ESD in patients with early gastric carcinoma(P＜0.05);The area under the curve(AUC)of miRNA-4319,miRNA-4262 and their combination for predicting recurrence after ESD in patients with early gastric carcinoma was 0.889(95％CI:0.854～0.918),0.914(95％CI:0.882～0.940)and 0.964(95％CI:0.940～0.980),respectively,which was superior to the individual predictions of miRNA-4319 and miRNA-4262 respectively(P＜0.05).Conclusion MiRNA-4319 and miRNA-4262 are low expressed in tissues of early gastric carcinoma patients,they are closely related to postoperative recurrence after ESD.

Purpose To evaluate the predictive value of multifunctional parameters of single photon emission computed tomography gated myocardial perfusion imaging(SPECT G-MPI)for major adverse cardiovascular events(MACE)in chronic kidney disease(CKD)with abnormal stress myocardial perfusion.Materials and Methods A total of 99 patients diagnosed with CKD from June 2017 to March 2024 who underwent stress and rest G-MPI indicating abnormal myocardial perfusion in Beijing Anzhen Hospital,Capital Medical University.The American Heart Association 17-segment 5-point method and PHASE software were used to obtain the left ventricular myocardial perfusion,functional and synchronization parameters.According to the occurrence of MACE,the patients were divided into MACE group and non-MACE group.Cox regression was used to analyze the predictors related to MACE.The receiver operator characteristic curve was used to analyze the performance of predictors,the survival curves were obtained by the Kaplan-Meier method,Log-rank test was used to compare the differences in different groups.Results Finally,we enrolled 99 CKD patients with abnormal stress myocardial perfusion.35 patients(35.35%)developed MACE during the follow-up period.Cox regression analysis showed that stress phase bandwidth(SPBW)(HR=1.015,95%CI 1.002-1.028)and sum difference score(SDS)(HR=1.105,95%CI 1.008-1.211)were independent risk factors for predicting MACE(both P<0.05).The optimal cut-off value of SPBW and SDS for predicting MACE were 69° and 6 points,the area under the curve was 0.801 and 0.778,respectively.The incidence of MACE in the SPBW≥69° group and SDS≥6 points group was higher than that in SPBW<69° group and SDS<6 points group(66.6%vs.13.2%,53.3%vs.20.4%,both P<0.05).Conclusion SPECT G-MPI multifunctional parameters can be used to predict the prognosis of CKD patients with abnormal stress myocardial perfusion.SPBW and SDS are independent risk factors for MACE in these patients.

Objective:To analyze the clinical and genetic features of a child with Primary ciliary dyskinesia (PCD) due to compound heterozygous variants of the CCDC39 gene and a 22q11.21 deletion, and to explore the potential role of the two types of variants in the formation of complex phenotypes. Methods:A child presented at the Shanxi Children′s Hospital in March 2025. due to multiple congenital anomalies was selected as the study subject. Peripheral blood samples were taken from the child and her parents and subjected to whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Effect of splicing variant was predicted using SpliceAI, and pathogenicity was assessed based on the ACMG guidelines. Copy number variation (CNV) analysis was also performed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No.: IRB-WZ-2025-019).Results:The patient has exhibited multiple features including severe pneumonia, bronchiectasis, localized pulmonary emphysema, scoliosis, tetralogy of Fallot, and atrial septal defect. Genetic testing revealed that she has harbored compound heterozygous variants of the CCDC39 gene, namely c. 1167+ 1G>A and c. 1009A>T, which were inherited from her father and mother, respectively, with the latter being a novel likely pathogenic variant. In addition, a heterozygous deletion of approximately 708 kb at 22q11.21 was detected. Conclusion:The coexistence of CCDC39 gene variants and a 22q11.21 deletion may underlay the development of complex clinical phenotypes in this child.

Objective:This study aims to initially establish a scoring system for comprehensively reflecting the severity of intracranial atherosclerotic lesions and to explore the correlation between this score and atherosclerotic risk factors as well as stroke events.Methods:This study retrospectively analyzed patients who underwent head and neck computer tomography angiography(CTA)examinations and had head MRI examinations within one month before or after the CTA examination from January 2021 to August 2024 in Beijing Hospital.An intracranial atherosclerosis disease score(ICADS)system was constructed based on the degree and number of vascular stenosis.The relationship between ICADS and atherosclerotic risk factors was explored by grouping patients according to the quartile of ICADS.Patients were divided into acute stroke group and non-acute stroke group to compare differences in ICADS and cerebrovascular disease risk factors between the two groups, and to investigate the correlation between stroke events and ICADS.Results:There were statistically significant differences in the proportions of patients with hypertension and diabetes among different ICADS groups.Multiple linear regression analysis showed that hypertension( B=1.17, 95% CI: 0.20-2.14, P<0.05)and diabetes( B=2.75, 95% CI: 1.85-3.64, P<0.001)were risk factors for higher ICADS.The ICADS was higher in the acute stroke group than in the non-acute stroke group(9 vs.6, P<0.001), and a higher ICADS was identified as a risk factor for stroke( OR=1.10, 95% CI: 1.07-1.14, P<0.001). Conclusions:ICADS can comprehensively reflect the severity of intracranial atherosclerotic lesions and is correlated with stroke events, making it useful for clinical screening of high-risk patients for stroke.