Mass spectrometry imaging （MSI） is an emerging molecular imaging technique that combines high spatial resolution and the ability to acquire molecular information. This technology can directly obtain spatial distribution maps of metabolites, proteins, lipids and other molecules in tumor tissues, reveal the abnormal molecular changes during the occurrence and development of liver cancer, and make up for the deficiency of information at the molecular level in traditional imaging （such as CT, MRI）. In liver cancer research, MSI has demonstrated unique advantages and application potential in early diagnosis and screening, precise classification, tumor heterogeneity analysis, and exploration of molecular mechanisms. The principle characteristics of MSI technology and its latest progress in the early diagnosis, classification and molecular mechanism research of liver cancer were reviewed, and the current challenges and future development directions were discussed, which aimed to provide a new perspective and theoretical basis for an in-depth understanding of the pathological mechanism of liver cancer and promoted its precise diagnosis and treatment.

The incidence rate of hepatic fibrosis remains at a high level， and there is still a lack of specific therapeutic drugs， posing a serious threat to human health. As a type of natural active components widely present in plants， flavonoids have multiple physiological functions such as antioxidant， anti-inflammatory， and anti-fibrotic activities， and a large number of studies have confirmed the anti-hepatic fibrosis effect of flavonoids. As for the mechanism of action， flavonoids can target the functions of hepatic stellate cells by inhibiting their proliferation and differentiation， promoting their apoptosis， regulating the level of autophagy， reducing the formation of extracellular matrix， and regulating iron metabolism in hepatic stellate cells， and meanwhile， they can inhibit chronic liver inflammatory response， improve oxidative stress status， regulate intestinal flora balance， and block epithelial-mesenchymal transition， thereby blocking the progression of fibrosis through multiple dimensions. At the level of signaling pathways， flavonoids mainly exert an anti-fibrotic effect by regulating the abnormal activation of the signaling pathways such as transforming growth factor-β1/Smad， Janus kinase/signal transducer and activator of transcription， nuclear factor erythroid 2-related factor 2， nuclear factor-kappa B， phosphatidylinositol 3-kinase/protein kinase B， mitogen-activated protein kinase， Wnt/β-catenin， and adenosine 5'-monophosphate-activated protein kinase. This article summarizes the research advances in the anti-fibrotic effect of flavonoids， in order to provide a theoretical basis for further exploring their medicinal potential.

ObjectiveTo investigate the association of the single nucleotide polymorphism （SNP） of the insulin-like growth factor binding protein-3 （IGFBP3） gene at rs10225396 （A>G） locus with the susceptibility to hepatocellular carcinoma， as well as its potential molecular regulatory mechanisms， and to provide novel genetic biomarkers and a theoretical basis for early screening and precise targeted therapy for hepatocellular carcinoma. MethodsA total of 192 patients with hepatocellular carcinoma who were admitted to The Affiliated Hospital of Yanbian University and Yanbian Cancer Hospital from January 2009 to August 2016 were enrolled as experimental group， and 190 healthy individuals who underwent physical examination in Physical Examination Center of Yanbian Hospital during the same period of time were enrolled as control group. Peripheral blood samples were collected from all subjects， and after DNA was extracted from whole blood， the DNA samples meeting quality standards were sent to Beijing Genomics Institute Research Center Co.， Ltd.， for Mass ARRAY mass spectrometry， while genotyping was completed. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. A binary Logistic regression model was used to analyze the association of the SNP of the IGFBP3 gene at rs10225396 locus with the susceptibility to hepatocellular carcinoma， and odds ratio （OR） and 95% confidence interval （CI） were calculated to assess the risk of developing hepatocellular carcinoma in individuals carrying different genotypes. ResultsThere were two alleles （G and A） at the rs10225396 locus of the IGFBP3 gene， yielding the three genotypes of AA， AG， and GG， and its genotype distribution was consistent with the Hardy-Weinberg equilibrium （χ²=0.072， P=0.789）. The stratified genetic analysis showed that carriers of the IGFBP3 rs10225396 AA genotype had a significant increased risk of hepatocellular carcinoma among individuals of age <63 years， male sex， smoking history， drinking history， and the Chinese Korean population （all P<0.001）. The binary Logistic regression analysis showed that after adjustment for related risk factors in the codominant model， the population with genotype AG and GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）， and in the dominant model， the population with genotype AG+GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）. ConclusionThrough a genotyping analysis of hepatocellular carcinoma patients and healthy individuals in Yanbian Korean Autonomous Prefecture of Jilin Province， China， this study shows that genotype AA at rs10225396 locus of the IGFBP3 gene is significantly associated with the susceptibility to hepatocellular carcinoma， and this genotype can significantly increase the risk of developing hepatocellular carcinoma with the presence of specific risk factors， which provides a potential genetic marker for early screening and precise treatment of hepatocellular carcinoma.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

Objective To investigate the effects of clesmatine on the myelination and neural oscillation-related firing activities during sleep in the hippocampus of adult APP/PS1 mice.Methods Oral administration of clemastine in drinking water was given to APP/PS1 mice for 3 months to enhance myelination in adulthood.Based on the treatment regimens,the mice were randomly assigned into APP/PS1 group,APP/PS1+clemastine group,and wild-type(WT)group.Local field potentials combined with three-dimensional acceleration of the head and neck were employed to determine the brain states,that is,wakefulness,non-rapid eye movement(NREM)sleep,REM sleep.In vivo multi-electrode arrays were utilized to continuously monitor neuronal firing activities in the dorsal hippocampus across the 3 sleep states.Results ① Oral clemastine administration via drinking water significantly increased MBP+protein expression levels in APP/PS1+Clemastine mice than the APP/PS1 controls(P<0.001).② Clemastine administration did not alter the time proportions of NREM sleep,REM sleep and wakefulness during the daytime phase in APP/PS1 mice(Ps>0.05).③ Clemastine administration obviously reduced the mean firing rate of hippocampal pyramidal cells(P<0.05)while increasing that of hippocampal interneurons(P<0.05)in APP/PS1 mice.④ Clemastine administration increased the occurrence rate of hippocampal sharp wave-ripple(SWR)oscillations during NREM sleep and specifically reduced the firing rate of pyramidal cells during SWR oscillations in APP/PS1 mice(P<0.05).⑤ Clemastine administration had no significant effect on the hippocampal neuronal firing activity during theta oscillation in REM sleep in APP/PS1 mice(Ps>0.05).Conclusion Clemastine administration not only enhances the adult myelination,but also rescues both the SWRs and associated hippocampal neuronal firing during NREM sleep in APP/PS1 mice.

ObjectiveTo investigate the effect of 1，25（OH）₂D₃ on the level of peroxisome proliferator-activated receptor-γ （PPAR-γ） in the liver， the phenotype of hepatic macrophages， and liver inflammation in a rat model of nonalcoholic steatohepatitis （NASH）， as well as the mechanism of 1，25（OH）₂D₃ improving liver inflammation. MethodsAfter 1 week of adaptive feeding， 24 specific pathogen-free Wistar rats were randomly divided into normal group ［choline-supplemented L-amino acid-defined （CSAA） diet］， normal+1，25（OH）₂D₃ group ［CSAA diet+1，25（OH）₂D₃］， model group ［choline-deficient L-amino acid-defined diet （CDAA） diet］， and model+1，25（OH）₂D₃ group ［CDAA diet+1，25（OH）₂D₃］， with 6 rats in each group. The dose of 1，25（OH）₂D₃ was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were measured， liver histopathology was observed， and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages， and ELISA was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in liver tissue， and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups， and the least significant difference t-test was used for further comparison； the Pearson method was used for correlation analysis. ResultsCompared with the normal group， the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT （P=0.019 and P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P<0.001）， as well as a significant increase in the level of TNF-α （P<0.001） and a significant reduction in the level of IL-4 in liver tissue （P=0.025）. The 1，25（OH）₂D₃ group had significant reductions in the serum levels of ALT （P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P=0.001）， the level of IL-1β （P<0.001） and a significant increase in the level of M2 hepatic macrophages （P=0.017）， the level of IL-10 （P=0.039）， the level of IL-4 （P<0.001）， the level of PPAR-γ （P=0.016）. There were significant interactions between CDAA diet-induced NASH model and 1，25（OH）₂D₃ in serum the levels of AST and ALT （P=0.007 and P=0.008）， the SAF scores of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， the level of M2 hepatic macrophages （P=0.008）， the ratio of M1 and M2 of hepatic macrophages （P=0.005）， the level of TNF-α （P<0.001）， the level of IL-10 （P=0.038）， the level of IL-4 （P<0.001） and the level of PPAR-γ （P=0.009）. The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages （r=-0.415， P=0.044） and was positively correlated with M2 hepatic macrophages （r=0.435， P=0.033）， IL-10 （r=0.433， P=0.035）， and IL-4 （r=0.532， P=0.007）. ConclusionThis study shows that 1，25（OH）₂D₃ improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.

Objective:To investigate the application value of nasolabial flaps in addressing tissue defects after resection of benign and malignant nasal vestibular lesions. Methods:The clinical data of patients with benign and malignant nasal vestibular lesions were analyzed retrospectively. There were 4 cases of squamous cell carcinoma, 2 cases of black hairy nevus and 1 case of chronic proliferative inflammatory lesions, all of which were repaired by adjacent nasolabial flap. Results:After 6 months of follow-up, none of the patients developed nasal vestibular contracture or nostril stenosis, and postoperative nasal ventilation function was good. Conclusion:The preoperative design of individual nasolabial flaps is very important for maintaining maxillofacial aesthetics, protectingthe nasolabial framework, and preserving postoperative nasal ventilation function.
Humans ; Retrospective Studies ; Middle Aged ; Nose Neoplasms/surgery* ; Surgical Flaps ; Male ; Female ; Adult ; Nose/surgery* ; Plastic Surgery Procedures/methods* ; Carcinoma, Squamous Cell/surgery* ; Aged ; Skin Transplantation

Objective To investigate the relationship between the expression of platelet autophagy related factors and peritoneal metastasis of gastric cancer.Methods The data of 360 patients with gastric cancer who underwent surgery in Hunan Provincial People's Hospital from January 2021 to May 2023 were reviewed.Patients were divided into non-peritoneal metastasis group(n=322)and peritoneal metastasis group(n=38)according to whether peritoneal metastasis occurred or not.The following information was collected:patient's personal information(i.e.age,sex,body mass index)and tumor characteristics(i.e.location,size,pathological type,histopathological differentiation,lymphatic infiltration).Platelets were collected from all subjects,and the levels of autophagy-associated protein 7(ATG7),benzalkonium chloride 1(BECN1),microtubule-associated protein 1 light chain 3(LC3)and sequestosome 1(p62)were measured by enzyme-linked immunosorbent assay(ELISA).Results Among the 360 patients included,peritoneal metastasis was detected in 38 cases.Compared with the non-peritoneal metastasis group,the peritoneal metastasis group exhibited decreased BMI(P<0.05),while the tumor size,non-ulcerative tumor,number of lymph node metastasis,infiltration depth,number of cases of lymphatic invasion,platelet count,platelet LC3-Ⅱ level,platelet ATG7 level and CEA level were increased(P<0.05).Multivariate logistic regression analysis showed that BMI(OR=1.094),lymphatic invasion(OR=2.658),and LC3-Ⅱ(OR=3.793)and ATG7(OR=2.010)were independent influencing factors for peritoneal metastasis in patients with gastric cancer(P<0.05).LC3-Ⅱ>2.59ng/ml had the highest ability to predict peritoneal metastasis in patients with gastric cancer(AUC=0.932),followed by ATG7(AUC=0.916).Conclusions Elevated levels of platelet LC3-Ⅱ and ATG7 are independently related to peritoneal metastasis in patients with gastric cancer,and can be used to predict the occurrence of peritoneal metastasis,which is helpful to guide individualized treatment.

Poloxamer， as a non-ionic surfactant， exhibits a unique triblock [polyethylene oxide-poly （propylene oxide）-polyethylene oxide] structure， which endows it with broad application potential in various fields， including solid dispersion technology， nanotechnology， gel technology， biologics， gene engineering and 3D printing. As a carrier， it enhances the solubility and bioavailability of poorly soluble drugs. In the field of nanotechnology， it serves as a stabilizer etc.， enriching preparation methods. In gel technology， its self-assembly behavior and thermosensitive properties facilitate controlled drug release. In biologics， it improves targeting efficiency and reduces side effects. In gene engineering， it enhances delivery efficiency and expression levels. In 3D printing， it provides novel strategies for precise drug release control and the production of high-quality biological products. As a versatile material， poloxamer holds promising prospects in the pharmaceutical field.

OBJECTIVE: To review clinical application and research progress of different types of intelligent responsive hydrogels in repairing articular cartilage injury. METHODS: The animal experiments and clinical studies of different types of intelligent responsive hydrogels for repairing articular cartilage injury were summarized by reviewing relevant literature at home and abroad. RESULTS: The intrinsic regenerative capacity of articular cartilage following injury is limited. Intelligent responsive hydrogels, including those that are temperature-sensitive, light-sensitive, enzyme-responsive, pH-sensitive, and other stimuli-responsive hydrogels, can undergo phase transitions in response to specific stimuli, thereby achieving optimal functionality. These hydrogels can fill the injured cartilage area, promote the proliferation and differentiation of chondrocytes, and expedite the repair of the damaged site. With advancements in cartilage tissue engineering materials research, intelligent responsive hydrogels offer a novel approach and promising potential for the treatment of cartilage injuries. CONCLUSION Intelligent responsive hydrogel is a kind of flexible, controllable, efficient, and stable polymer, which has similar structure and functional properties to articular cartilage, and has become one of the important biomaterials for cartilage repair. However, there is still a lack of unified treatment standards and simple and efficient preparation technology.
Hydrogels/therapeutic use* ; Cartilage, Articular/injuries* ; Tissue Engineering/methods* ; Humans ; Animals ; Chondrocytes/cytology* ; Biocompatible Materials/chemistry* ; Tissue Scaffolds/chemistry*