[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。

Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance, making them an invaluable asset in the era of antibiotic resistance. Numerous depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models. Additionally, some formulation approaches have been developed for improved stability and activity of depolymerases. However, depolymerase formulation is limited to liquid dosage form and remains in its infancy, posing a significant hurdle to their clinical translation, compounded by challenges in their applicability and manufacturing. Future development must address these obstacles for clinical utility. Here, after unravelling the history, diversity, and therapeutic use of depolymerases, we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases. Finally, the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

Objective: To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone (GnRH) antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome (OHSS). Methods: A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group (n=51) received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group (n=48) were given cetrorelix of 0.25 mg subcutaneously daily for 3 days. Both groups received support therapy combined with embryo cryopreservation. The incidence of OHSS was surveyed. And the serum concentration of estradiol, LH and progesterone on days 3, 5 and 8 after oocytes retrieval were measured. Results: There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group [11.8%(6/51)] and GnRH antagonist group [10.4%(5/48);P>0.05]. The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were (1 417±3 543) versus (15 210±9 921) pmol/L, (1 692±4 330) versus (18 680±11 567) pmol/L, (239±336) versus (3 582±5 427) pmol/L, respectively;compared with GnRH antagonist group, the estradiol level was significantly lower in the letrozole group (all P<0.01). The luteinizing hormone level in the letrozole group were (0.46±0.40), (0.56±0.55)and (0.67±0.58) U/L on days 3,5 and 8 after oocytes retrieval, which were significantly higher than those of GnRH antagonist group [(0.28±0.28), (0.30±0.19) and (0.45±0.37) U/L, respectively; all P<0.05]. There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group (all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval (P<0.05). Conclusion Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS, faster and cheaper to use, but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.

Objective The paper proposed suggestions and measures for hospital scientific research management by statistical analyzing all the papers published from 2009 to 2013.Method By referring to research database of this hospital and by using Microsoft Excel,this research calculated the frequency distributions of different variables including quantity,publisher,disciplinary subject,and the author title as well as core author.Result 772 papers were published from 2009 to 2013,mainly in local periodicals.75.52％ of the title of first author are high-level or intermediate-level;86 core authors published 378 papers,account for 48.96％ of the total amount.Conclusion The number of research papers is increasing year by year.but the quantity and quality are still low.The research administorsshould take measures to encourage researchers to publish quality papers in periodicals with higher standards.

Objective To evaluate the role of chemokine receptor CXCR4 in spinal dorsal horn in the development of morphine tolerance in rats with bone cancer pain (BCP).Methods Forty female Sprague-Dawley rats,weighing 180-220 g,were equally randomized into 5 groups using a random number table:sham operation group (group S),BCP group (group B),BCP + AMD3100 (specific CXCR4 antagonist) group (group BA),BCP + morphine group (group BM),BCP + morphine + AMD3100 group (group BMA).BCP was induced by injecting Walker 256 mammary gland cancer cell suspension (4 × 105 cells/ml) 5 μl into the bone marrow of the right tibia of rats anesthetized with chloral hydrate.On 6 days after injection of mammary gland cancer cells,AMD3100 2 mg/kg was intraperitoneally injected twice a day for 9 days in BA group,and morphine 10 mg/kg was subcutaneously injected twice a day for 9 days in BM group.AMD3100 was intraperitoneally injected and morphine was subcutaneously injected as previously described at the corresponding time point in BMA group.Before injection of mammary gland cancer cells (T0) and on 4,6,8,10,12 and 14 days after injection of mammary gland cancer cells (T1-6),paw withdrawal threshold to von Frey hair mechanical stimulation (PWMT) was measured.The rats were then sacrificed and L3-5 segments of the spinal cord were removed for determination of c-fos expression in spinal dorsal horn using immunofluorescence.Results Compared with S group,PMWT was significantly decreased at T2-6 in B and BA groups and at T4-6 in BM group,and c-fos expression was up-regulated at T6 in BM group (P ＜0.01).PMWT was significantly higher at T3-5 in BM group and at T3-6 in BMA group than in group B (P ＜ 0.01).Compared with BM group,PMWT was significantly increased at T5,6 and c-fos expression was down-regulated at T6 in BMA group (P ＜ 0.01).Conclusion Chemokine receptor CXCR4 in spinal dorsal horn is involved in the development of morphine tolerance in rats with BCP and the mechanism may be related to activation of c-fos.