Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective: To explore the association between sleep quality and dry eye symptoms in adolescents,so as to provide the evidence for reducing the prevalence of dry eye symptoms. Methods: The study population was adolescents aged 12-24 years from the Psychology and Behavior Investigation of Chinese Residents (PBICR) survey, which was conducted from 20 June to 31 August 2022. A stratified random sampling and quota sampling method was used to select 6 456 adolescents within mainland China. The Ocular Surface Disease Index (OSDI) and Brief version of the Pittsburgh Sleep Quality Index (B-PSQI) were used to assess dry eye symptoms and sleep quality. Multiple Logistic regression model was used to explore the relationship between sleep quality and dry eye symptoms in adolescents. The influence of gender on the association was explored by using interaction terms. Results: A total of 2 815 adolescents reported having dry eye symptoms, with a prevalence of 43.6%. Logistic regression analysis results showed an increased risk of exacerbation of dry eye symptoms in adolescents with poor sleep quality. The OR (95% CI ) for mild, moderate, and severe dry eye symptoms groups were 1.39(1.16-1.67), 1.52(1.28-1.81), and 2.35(2.02-2.72), respectively, compared with the ocularly normal group ( P <0.05). There was a significant interaction between sleep quality and gender on dry eye symptoms in adolescents ( P <0.01). Conclusions Sleep quality is associated with dry eye symptoms in adolescents, and those with poor sleep quality have a higher risk of dry eye symptoms. The effect of sleep quality on dry eye symptoms is greater in boys.

Objective:To explore the clinical efficacy of biopsy forceps polypectomy with submucosal injection for diminutive colorectal polyps.Methods:The patients with diminutive colorectal polyps (long diameter≤5 mm in size) who received polypectomy in Quanzhou First Hospital Affiliated to Fujian Medical University from May 2021 to May 2022 were prospectively recruited and divided into the observation group (biopsy forceps polypectomy with submucosal injection) and the control group (traditional biopsy forceps polypectomy). The location, morphology, long diameter, the complete polypectomy rate under direct vision, the time of resection and endoscopy withdrawal, pathological results, specimen collection rate, the incidence of complications and endoscopic treatment cost were analyzed. The clinical efficacy of the two methods were compared.Results:A total of 292 patients were included in the study, with 146 in the observation group and 146 in the control group. There were 258 polyps in the observation group and 252 polyps in the control group. The complete polypectomy rate was higher in the observation group than that in the control group [100.0% (258/258) VS 90.1% (227/252), χ2=26.915, P=0.001] with clear vision. The incidence of complications in the observation group was lower than that in the control group (1/146 VS 13/146, χ2=10.804, P=0.001) , along with the lower treatment cost (173.7±15.9 yuan VS 184.0±53.8 yuan, Z=-2.777, P=0.005). The resection time in the observation group was longer than that in the control group, but the difference was not statistically significant [10 (9,11) min VS 9 (9,11) min, Z=-0.528, P=0.597]. There was no significant difference in the polyp position, long diameter, morphology, pathological classification, or the specimen collection rate between the two groups ( P>0.05). Conclusion:Biopsy forceps polypectomy with submucosal injection is safe for diminutive colorectal polyps, and it demonstrates a higher complete polypectomy rate, lower complication rates, and reduced treatment costs compared with traditional biopsy forceps polypectomy. It is a new perspective for managing diminutive colorectal polyps.

Objective:To explore the clinical efficacy of biopsy forceps polypectomy with submucosal injection for diminutive colorectal polyps.Methods:The patients with diminutive colorectal polyps (long diameter≤5 mm in size) who received polypectomy in Quanzhou First Hospital Affiliated to Fujian Medical University from May 2021 to May 2022 were prospectively recruited and divided into the observation group (biopsy forceps polypectomy with submucosal injection) and the control group (traditional biopsy forceps polypectomy). The location, morphology, long diameter, the complete polypectomy rate under direct vision, the time of resection and endoscopy withdrawal, pathological results, specimen collection rate, the incidence of complications and endoscopic treatment cost were analyzed. The clinical efficacy of the two methods were compared.Results:A total of 292 patients were included in the study, with 146 in the observation group and 146 in the control group. There were 258 polyps in the observation group and 252 polyps in the control group. The complete polypectomy rate was higher in the observation group than that in the control group [100.0% (258/258) VS 90.1% (227/252), χ2=26.915, P=0.001] with clear vision. The incidence of complications in the observation group was lower than that in the control group (1/146 VS 13/146, χ2=10.804, P=0.001) , along with the lower treatment cost (173.7±15.9 yuan VS 184.0±53.8 yuan, Z=-2.777, P=0.005). The resection time in the observation group was longer than that in the control group, but the difference was not statistically significant [10 (9,11) min VS 9 (9,11) min, Z=-0.528, P=0.597]. There was no significant difference in the polyp position, long diameter, morphology, pathological classification, or the specimen collection rate between the two groups ( P>0.05). Conclusion:Biopsy forceps polypectomy with submucosal injection is safe for diminutive colorectal polyps, and it demonstrates a higher complete polypectomy rate, lower complication rates, and reduced treatment costs compared with traditional biopsy forceps polypectomy. It is a new perspective for managing diminutive colorectal polyps.

Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed with α-,β-,y-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm iso-mers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+y-CD+Cu-H]+with separation resolution(Rp-p)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+y-CD+Ca-H]+with Rp-p of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R2＞0.99)was ob-tained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.

Objective: To study the effects of different concentrated sulfuric acid etching durations on the shear bond strength between polyether-ketone-ketone (PEKK) and dentin, providing a scientific basis for the clinical bonding procedures of PEKK prosthesis. Methods: Forty-four PEKK specimens were prepared and randomly divided into four groups: group A was the control group, which was only polished with abrasive papers, group B, group C and group D were experimental groups, which were etched by 98% concentrated sulfuric acid for 5 s, 30 s and 60 s, respectively. In addition, one sample was randomly selected from each group, and the profile was prepared by a slow cutting machine. The surface morphology of the profile was observed under SEM. After the four groups of specimens and dentin were bonded by resin, they were soaked in distilled water at 37 ℃ for 24 h. After the shear bonding strengths were measured, the fracture interfaces of the specimens were examined by the scanning electron microscopy and stereomicroscopy, and failure models of bonding were analyzed. Results: After acid etching treatments, the cross-sectional images in group B presented uniform spongy shapes, while the cross-sectional images in group C and group D showed destructive pore structures. The shear bond strengths of group B (16.84 ± 1.84) MPa, group C (12.33 ± 1.22) MPa and group D (6.44 ± 1.18) MPa were higher than that of group A (3.99 ± 1.06) MPa (P < 0.05). The highest shear bond strength was observed in group B (16.84 ± 1.84) MPa. Conclusion The surface treatment of 98% sulfuric acid etching for 5 s manifested the best bond strength between PEKK and dentin.

Diabetic nephropathy (DN) is one of the major microvascular complications in diabetic patients, and it is also the main global cause of chronic kidney disease(CKD) and end-stage renal disease(ESRD). Albuminuria and estimated glomerular filtration rate (eGFR) are currently recognized as clinically diagnosed early DN, but their sensitivity and specificity are poor. Therefore, it is very important to find new biomarkers to reflect the potential diabetic nephropathy in the clinical silent period.

Abstract China has one of the world’s highest prevalence of myopia in children and adolescents, and children are developing myopia earlier. Myopia has become a important issues affecting children and adolescents health, as well as a significant public health concern. There has been continuing debate over the role of nature and nurture in the aetiology of myopia, growing evidence showed that environmental factors has a determine effect on myopia.The randomized controlled trials has assured the relationship between time outdoors and myopia. Based on reviewed published articles, survey and intervention studies and school health practices, according to the principle of school organization, student participation and family cooperation, the authors proposed outdoors activities as initiative for myopia prevention and control in children and adolescents. The detail recommendation contents, levels were list out.