[摘 要] 目的：探讨同源异型盒蛋白D11（HOXD11）对Ki-67的转录调控作用及其对喉鳞状细胞癌（LSCC）细胞恶性生物学行为的影响和机制。方法：结合高通量测序数据，通过GEO、UALCAN数据库分析HOXD11在LSCC中差异表达。收集2022年1月至2025年1月联勤保障部队第九八〇医院手术切除的60例LSCC患者的癌及癌旁组织标本，以及人LSCC细胞系AMC-HN-8、TU-177、TU-686和人正常喉上皮细胞（HNLEC），构建敲低或过表达HOXD11的细胞系，将细胞分为对照组、HOXD11敲低组及HOXD11过表达组。通过RT-qPCR法检测HOXD11和Ki-67基因在LSCC组织和细胞中mRNA表达水平，免疫组织化学（IHC）法分析两者在LSCC组织中的蛋白表达及分布，WB法进一步验证蛋白差异表达。采用MTS、克隆形成实验及Transwell实验分别检测敲低或过表达HOXD11对LSCC细胞增殖、迁移与侵袭的影响。通过双萤光素酶报告基因实验和染色质免疫沉淀（ChIP）实验验证HOXD11对Ki-67启动子活性的调控作用。结果：GEO和UALCAN数据库分析表明，HOXD11在LSCC中高表达（P < 0.01）。在LSCC组织中HOXD11和Ki-67 mRNA和蛋白表达均显著高于癌旁组织（均P < 0.01），同时，两者表达水平之间存在正相关（r = 0.26，P < 0.05）；LSCC细胞系中HOXD11 mRNA表达显著高于HNLEC（均P < 0.01）。敲低HOXD11显著抑制LSCC细胞的增殖、迁移和侵袭能力（均P < 0.01），而过表达HOXD11则促进细胞的这些恶性生物学行为（均P < 0.01）。双萤光素酶报告基因实验及ChIP实验均证实，HOXD11可直接结合到Ki-67启动子区上，调控其表达（P < 0.01）。回复实验显示，过表达Ki-67可部分逆转敲低HOXD11对LSCC细胞增殖、迁移与侵袭的抑制作用（均P < 0.01）。结论：HOXD11在LSCC组织及细胞系中均呈高表达，其机制在于通过直接调控Ki-67的转录活性，从而增强LSCC细胞的增殖、迁移及侵袭能力。

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.

Achieving the functional cure （clinical cure） of hepatitis B is the primary goal of current clinical hepatology and novel drug research and development. In 2023， the Center for Drug Evaluation， National Medical Products Administration， issued Technical guidance for clinical trials of therapeutic drugs for chronic hepatitis B virus infection to establish a top-level regulatory framework. Supporting Q&A documents for public consultation were released in July 2026 to provide practical policy guidance for the research and development of novel hepatitis B drugs， which has far-reaching implications for clinical investigators， innovative pharmaceutical enterprises， and the development of hepatology.

Food safety problems caused by foodborne pathogenic bacteria pose a serious threat to public health,creating an urgent need to develop testing methods and techniques with excellent performance and are simple to use and of affordable cost.Traditional testing methods,such as isolation and culture,morphological observation,biochemical identification,and serological tests,have many limitations,including complex procedures,reliance on specialized technical equipment and personnel,and long turnaround time,rendering them inadequate for meeting current and future testing demands.Therefore,it is particularly important to develop simple,rapid,and highly sensitive methods for analyzing pathogenic bacteria.The fusion of nucleic acid aptamers and nanozymes brings new ideas for the rapid testing of pathogenic bacteria.On one hand,aptamers offer specific recognition capability for target bacteria and can be combined with various nucleic acid signal amplification techniques.On the other hand,the enzyme-like catalytic activity and signal amplification effect of many nanomaterials provide a basis for highly sensitive testing.This review highlights the application potential of nanozyme?aptamer coupling systems in the field of microbial analysis by briefly summarizing the latest research progress in the use of nanozymes combined with aptamers for the detection of foodborne pathogenic bacteria.First of all,two main approaches to conjugating nanozymes with aptamers are introduced.Then,the testing mechanisms and typical applications of nanozyme?aptamer coupling systems for foodborne pathogenic bacteria are discussed.Finally,future development trends and existing challenges are disucssed from four perspectives,including specificity,high sensitivity,high throughput,and intelligent detection.This review aims to provide a useful reference for the fusion of nanozymes and aptamers and for the development of on-site rapid testing techniques for foodborne pathogens,and to encourage broader academic interest to further advance this promising research field.

Objective To explore the effect of nuclear respiratory factor 1(NRF1)activation of ATP binding cas-sette transporter C1(ABCC1)transcription on cisplatin resistance in lung adenocarcinoma cells and its potential mechanisms.Methods The expression levels of ABCC1 in lung adenocarcinoma tumor tissues were analyzed by on-cogenomic datasets.Cells were grouped into:sh-NC,sh-ABCC1,sh-NC+oe-NC,sh-NRF1+oe-NC and sh-NRF1+oe-ABCC1.Real-time polymerase chain reaction(RT-qPCR)was used to detect the expression of ABCC1 in lung adenocarcinoma cells.Cisplatin-resistant lung adenocarcinoma cell strains were constructed to detect the expression level of ABCC1.Cell proliferation,migration and invasion were assessed by colony formation and Transwell assay.The IC50 values of drug-resistant lung adenocarcinoma cells treated with different doses(0,0.001,0.002,0.004,0.008,0.016 and 0.032 mg/mL)of cisplatin were detected by CCK-8 assay.Western blot was used to detect the protein expression of epithelial-mesenchymal transition markers(E-cadherin,N-cadherin).Dual luciferase and ChIP assays were performed to verify the binding relationship between NRF1 and ABCC1.Results ABCC1 was highly expressed in lung adenocarcinoma tumor tissues and cells.Compared with cisplatin-sensitive lung adenocarci-noma cells,ABCC1 was highly expressed in cisplatin-resistant lung adenocarcinoma cells,and knockdown of ABCC1 significantly inhibited cell proliferation,migration and invasion,and increased the expression of E-cadherin(P<0.05)and decreased the expression of N-cadherin(P<0.05).Knockdown of ABCC1 significantly increased the sensitivity of lung adenocarcinoma cells to cisplatin(P<0.05).In addition,dual luciferase and ChIP experi-ments confirmed the binding relationship between NRF1 and ABCC1 promoter de-binding,and NRF1 could activate the transcription of ABCC1.Knockdown of NRF1 attenuated the inhibitory effect of over-expressed ABCC1 on the proliferation,migration,invasion and cisplatin-resistance of lung adenocarcinoma cells(P<0.05).Conclusions This study revealed the effect of the NRF1/ABCC1 axis enhancement is a potential strategy to overcome the barrier of cisplatin-resistance in chemotherapy of lung adenocarcinoma.

Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.

Objective:To study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.

[Objective]To investigate the protective effect of overexpressed miRNA-200a&c on Angiostrongylus cantonensis-induced demyelinating optic neuritis in Balb/c mice.[Methods]SPF-grade Balb/c mice(2-3 weeks old)were divided into four groups:a normal group,and three A.cantonensis-infected groups at 7,14,and 21 days post-infection(dpi).Body weight,survival status,neurobehavioral scores,and visual function scores were recorded.Visual evoked potential(VEP)was used to detect visual damage,and transmission electron microscope(TEM)was applied to observe ocular structural changes.On day 7 post-infection,mice were stereotactically injected with exogenous miRNA-200a&c mimics into the lateral ventricle,and then divided into four groups:normal control,A.cantonensis-infected(AC-21 dpi),A.cantonensis-infected+negative control(AC+NC),and A.cantonensis-infected+overexpressed miRNA-200a&c(AC+miRNA-200a&c)mimics.VEP and TEM were repeated to assess visual damage and ocular structural changes.Immunofluorescence was performed to quantify retinal ganglion cells(RGCs)and oligodendrocytes(OLs)in the optic nerve.[Results]At 21 dpi,some mice exhibited complete eyelid closure(32.52±4.67)%or ocular atrophy(15.79±3.23)%,weight loss(P＜0.05)and altered consciousness.Neurobehavioral scores significantly decreased(P＜0.01),with a 68%decline in rotarod performance;some mice even displayed hemiplegia,slowed movement,ataxia,and directional deficits.Additionally,a subset of mice showed diminished sensory responses,unilateral vision loss(83%reduction in optokinetic threshold),and impaired visual function(P＜0.05).VEP results revealed a mild prolongation of latency in infected mice at 21 dpi(P＜0.05),predominantly affecting one eye.Following overexpression of miRNA-200a&c,compared with the 21 dpi group,VEP showed significantly shortened P1 latency(P＜0.05);TEM showed alleviated cytoplasmic swelling of RGCs,and improved compactness and uniformity of myelin sheath(P＜0.05);immunofluorescence showed increased numbers of RGCs and OLs with improved cell alignment(P＜0.05).[Conclusions]A.cantonensis infection induces demyelinating optic neuritis in Balb/c mice.Overexpression of miRNA-200a&c alleviates the resulting damage and ameliorates ocular injury.

Hypericum attenuatum Choisy.is dry whole grass of the genus Hypericum L.,is a kind of commonly used folk medicinal herbs more than 2400 years.And it is often used to treat heart disease,hemostasis,scald.Based on a review of domestic and international literature,the main chemical components of Hypericum attenuatum Choisy.include PPAPs,flavonoids,and volatile oil,of which PPAPs and xanthone have received the attention of a large number of scholars because of their complex and novel structures and unique pharmacological effects.Modern pharmacological studies have shown that Hypericum attenuatum Choisy.exerts various pharmacological activities,including anti-arrhythmia,reducing blood sugar,anti-tumor,anti-virus,anti-inflammation,as well as the treatment of depression.As a valuable folk medicine,there is relatively little related traditional Chinese medicine products,this review focus on its phytochemistry,and pharmacology,providing a comprehensive perspective and novel ideas for exploring its current and potential applications.

Objective To explore the repair effect and mechanism of human amniotic mesenchymal stem cells(hAMSCs)on endometrial injury.Methods hAMSCs were isolated using a two-enzyme digestion and then cultured.The third-passage(P3)cells were harvested to detect the surface markers by flow cytometry and to identify their trilineage differentiation potentials.Eighteen nulliparous female SD rats(8～9 weeks old,weighing 250～280 g)were randomly divided into 3 groups(n=6):normal control group,model group,and hAMSCs group.A rat model of intrauterine adhesions(IUA)was established in SD rats by using curettage combined with lipopolysaccharide(LPS)infection.In 2 weeks after modeling,the hAMSCs group received a bilateral uterine horn transplantation of 0.2 mL hAMSCs(1.0×10? cells/mL),while the model group received a same volume of PBS into both uterine horns.All rats were sacrificed in 2 weeks after transplantation.HE and Masson staining was used to observe endometrial thickness and gland number as well as endometrial fibrosis area.RT-qPCR and Western blotting were performed to detect the mRNA and protein levels of TGF-β1,Smad3,Smad7,epithelial-mesenchymal transition(EMT)markers(E-cadherin,Vimentin),fibrosis factor α-SMA,and endometrial estrogen receptor(ER)and progesterone receptor(PR)in endometrial tissues.Results The obtained cells were identified as hAMSCs due to the characteristics of surface markers and differentiation potentials.Compared with the normal control group,the model group showed decreased endometrial thickness,reduced gland number,increased fibrosis area,and enhanced mRNA and protein levels of fibrosis-related factors TGF-β1,Smad3,Vimentin,and α-SMA(P<0.01),while down-regulation of fibrosis-inhibiting molecule Smad7,the EMT marker E-cadherin,and endometrial receptors ER and PR at both mRNA and protein levels(P<0.01).hAMSCs transplantation increased endometrial thickness and gland number,decreased fibrosis area,and down-regulated mRNA expression of the aforementioned fibrosis-related factors(P<0.01),and up-regulated the mRNA expression levels of Smad7,E-cadherin,ER,and PR(P<0.01).The hAMSCs group also exhibited obviously down-regulated protein levels of TGF-β1,Smad3,and α-SMA(P<0.05),while enhanced protein levels of Smad7 and PR(P<0.05).Conclusion Intrauterine transplantation of hAMSCs can promote the repair of endometrial injury,and inhibits endometrial EMT and fibrosis through the TGF-β1/Smad7 signaling pathway.