[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 and aims:Liver fibrosis is a prevalent pathological stage of various chronic liver diseases and has the potential to progress to liver cirrhosis and hepatocellular carcinoma.However,experimental models for in vivo research are limited.Unexpectedly,increased liver inflammation and fibrosis were previously observed in mice treated with aluminum adjuvant(commercial Imject Alum,a mixture of Al(OH)3 and Mg(OH)2).Our study aimed to reveal the pathogenesis and pathological features of Imject Alum-induced liver injury and evaluate its potential as an experimental model of fibrotic liver disease.Methods and materials:C57BL/6J mice were randomly divided into the following four groups:(ⅰ)control group,which received phosphate-buffered saline injections on days 1,12,26,40,and 54;(ⅱ)Imject Alum(Al(OH)3 160 mg/kg)D26 group,which was administered with Imject Alum(Al(OH)3 160 mg/kg)on days 1,12,and 26;(ⅲ)Imject Alum(Al(OH)3 80 mg/kg)D54;and(ⅳ)Imject Alum(Al(OH)3 160 mg/kg)D54 groups,which were treated with 80 mg/kg and 160 mg/kg of Imject Alum(Al(OH)3),respectively,on days 1,12,26,40,and 54.All reagents were delivered by intraperitoneal injection.Serum biochemical pa-rameters,liver pathology,and expression of genes related to inflammation and fibrogenesis were eval-uated.Transcriptome sequencing was performed.The genetic characteristics of the Imject Alum-induced liver lesions in the existing fibrosis model and patients with cirrhosis were determined.Results:Administration of Imject Alum(Al(OH)3 160 mg/kg)at certain points for 54 days led to extensive hepatic inflammation and fibrosis,accompanied by disturbed bile acid metabolism in mice.Moreover,Imject Alum aggravated liver inflammation and injury by activating the pyroptosis-related inflamma-some pathway.Transcriptome analysis revealed that Imject Alum-induced liver lesions had differentially expressed genes that were significantly enriched in pathways related to inflammation,fibrogenesis,and multiple metabolic processes.Moreover,Imject Alum-induced liver lesions exhibited gene signatures similar to those of existing fibrosis models and patients with cirrhosis.Conclusions:Aluminum adjuvant(Imject Alum;Al(OH)3 160 mg/kg)administration at certain points for 54 days resulted in notable liver injury,inflammation,and fibrosis.This model had similar gene expression characteristics with existing fibrosis models and liver samples from patients with cirrhosis.Overall,aluminum adjuvant(Imject Alum)-induced mouse model may be a novel approach for estab-lishing a liver fibrosis animal model.

Objective To explore the effect of stratified out-of-hospital health management led by case health manager on the health behaviour ability of the patients with chronic diseases.Methods A convenience sampling method was employed to select 481 patients with chronic diseases who underwent physical examinations at outpatient department of a Tier-IIIA hospital from April 2022 to April 2023.A health management team led by case health managers conducted questionnaire survey to investigate the individual characteristics of the patients,established personal record based on the physical examination,and implemented stratified out-of-hospital health management for the patients.The intervention lasted for 12 months.The health behaviour ability and chronic disease self-management efficacy of the patients before and after the intervention were compared with.Results After the case manager-led stratified out-of-hospital health management,the health behaviour ability of patients with chronic diseases was stronger than that before the implementation,the self-management efficacy of chronic diseases was better than that before the implementation,and the patients'satisfaction was higher than that before the implementation(all P<0.001).Conclusion Stratified out-of-hospital health management led by a case health manager can improve the health behaviour ability and self-management efficacy of the patient with chronic diseases,thereby improve the patients'satisfaction.

Objective:To analyze the latent profile characteristics of self-management ability in patients with metabolic-associated fatty liver disease (MAFLD) and explore its influencing factors.Methods:This was a cross-sectional study. A total of 311 patients with metabolic-associated fatty liver disease (MAFLD) were selected from the First Affiliated Hospital of Sun Yat-sen University (including those receiving treatment and undergoing physical examinations) between August and October 2024. Data were collected using a general information questionnaire, the self-management Scale for Patients with Non-Alcoholic Fatty Liver Disease, and the Social Support Rating Scale. After excluding 51 patients due to incomplete questionnaire responses or logical inconsistencies, 260 patients were finally included in the analysis. Latent profile analysis was used to identify potential categories of patients′ self-management abilities. With the latent categories as the dependent variable and items with P<0.05 in univariate analysis as independent variables, a multivariate logistic regression analysis (with the "poor self-management group" as the reference group) was performed to explore the influencing factors. Results:Among the 260 participants included in the study, three potential categories of self-management behaviors were finally identified, namely the active self-management group with 106 cases (40.8%), the moderate self-management group with 118 cases (45.4%), and the passive self-management group with 36 cases (13.8%).Results of multivariate logistic regression analysis showed that, compared with the passive self-management group:Patients who resided in rural areas ( OR=0.130, 95% CI: 0.040-0.420), often stayed up late ( OR=0.200, 95% CI: 0.060-0.590), or had an average daily sleep duration of≤5 hours ( OR=0.160, 95% CI: 0.050-0.510) had a significantly lower probability of belonging to the "active self-management group";In contrast, patients with an education level of senior high school or above ( OR=7.530, 95% CI: 1.740-34.160) or a higher total score of social support ( OR=1.120, 95% CI: 1.030-1.210) had a significantly higher probability of being in the "active self-management group" (all P<0.05). Conclusion:There is heterogeneity in self-management ability among patients with metabolic associated fatty liver disease (MAFLD). Residential area, educational level, frequency of staying up late, average daily sleep duration, and social support are influencing factors of patients′ self-management ability.

Diamond-Blackfan anemia(DBA),also known as congenital pure red cell aplasia,is a rare genetic disorder characterized by bone marrow failure,congenital anomalies,and severe red blood cell abnormalities.The rarity of the condition,and consequently limited patient pool and scarcity of research models,means that the pathogenic mechanisms associated with genetic mutations in DBA remain uncertain,and the clinical treatment options are limited.This review synthesizes the findings from zebrafish,mouse,and human cellular models of DBA mutations.We clarify the pathogenic mechanisms and monitor the progression of drugs into clinical trials,thereby aiding further in-depth explorations into the etiology and therapeutic advancements for DBA.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

Diamond-Blackfan anemia(DBA),also known as congenital pure red cell aplasia,is a rare genetic disorder characterized by bone marrow failure,congenital anomalies,and severe red blood cell abnormalities.The rarity of the condition,and consequently limited patient pool and scarcity of research models,means that the pathogenic mechanisms associated with genetic mutations in DBA remain uncertain,and the clinical treatment options are limited.This review synthesizes the findings from zebrafish,mouse,and human cellular models of DBA mutations.We clarify the pathogenic mechanisms and monitor the progression of drugs into clinical trials,thereby aiding further in-depth explorations into the etiology and therapeutic advancements for DBA.

Objective:To analyze the latent profile characteristics of self-management ability in patients with metabolic-associated fatty liver disease (MAFLD) and explore its influencing factors.Methods:This was a cross-sectional study. A total of 311 patients with metabolic-associated fatty liver disease (MAFLD) were selected from the First Affiliated Hospital of Sun Yat-sen University (including those receiving treatment and undergoing physical examinations) between August and October 2024. Data were collected using a general information questionnaire, the self-management Scale for Patients with Non-Alcoholic Fatty Liver Disease, and the Social Support Rating Scale. After excluding 51 patients due to incomplete questionnaire responses or logical inconsistencies, 260 patients were finally included in the analysis. Latent profile analysis was used to identify potential categories of patients′ self-management abilities. With the latent categories as the dependent variable and items with P<0.05 in univariate analysis as independent variables, a multivariate logistic regression analysis (with the "poor self-management group" as the reference group) was performed to explore the influencing factors. Results:Among the 260 participants included in the study, three potential categories of self-management behaviors were finally identified, namely the active self-management group with 106 cases (40.8%), the moderate self-management group with 118 cases (45.4%), and the passive self-management group with 36 cases (13.8%).Results of multivariate logistic regression analysis showed that, compared with the passive self-management group:Patients who resided in rural areas ( OR=0.130, 95% CI: 0.040-0.420), often stayed up late ( OR=0.200, 95% CI: 0.060-0.590), or had an average daily sleep duration of≤5 hours ( OR=0.160, 95% CI: 0.050-0.510) had a significantly lower probability of belonging to the "active self-management group";In contrast, patients with an education level of senior high school or above ( OR=7.530, 95% CI: 1.740-34.160) or a higher total score of social support ( OR=1.120, 95% CI: 1.030-1.210) had a significantly higher probability of being in the "active self-management group" (all P<0.05). Conclusion:There is heterogeneity in self-management ability among patients with metabolic associated fatty liver disease (MAFLD). Residential area, educational level, frequency of staying up late, average daily sleep duration, and social support are influencing factors of patients′ self-management ability.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

Objective To explore the effect of stratified out-of-hospital health management led by case health manager on the health behaviour ability of the patients with chronic diseases.Methods A convenience sampling method was employed to select 481 patients with chronic diseases who underwent physical examinations at outpatient department of a Tier-IIIA hospital from April 2022 to April 2023.A health management team led by case health managers conducted questionnaire survey to investigate the individual characteristics of the patients,established personal record based on the physical examination,and implemented stratified out-of-hospital health management for the patients.The intervention lasted for 12 months.The health behaviour ability and chronic disease self-management efficacy of the patients before and after the intervention were compared with.Results After the case manager-led stratified out-of-hospital health management,the health behaviour ability of patients with chronic diseases was stronger than that before the implementation,the self-management efficacy of chronic diseases was better than that before the implementation,and the patients'satisfaction was higher than that before the implementation(all P<0.001).Conclusion Stratified out-of-hospital health management led by a case health manager can improve the health behaviour ability and self-management efficacy of the patient with chronic diseases,thereby improve the patients'satisfaction.