[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。

Objective:To reveal the evolutionary characteristics of tissue engineering strategies for spinal cord injury repair from basic research to clinical application, based on the core database of Web of Science.Methods:Key words such as ′′scaffold′′, ′′growth factors′′, ′′stem-cells′′ and ′′progenitors′′ were searched for in the core database of Web of Science before December 31, 2024, with different combinations of keywords used. The search range was set to ′′Topic′′, and the category was ′′Article′′. The original literature data were screened, sorted and formatted using Excel and self-made R program. High-frequency words and annual scientific output were analysed using the Bibliometrix software package. The literature bird online analysis tool was used to screen the high-impact team and draw the author relationship map.Results:A total of 62 142 articles were retrieved, involving multiple disciplines such as biology and medicine. scaffold (17 times), growth factors (9 times) and stem-cells (37 times) were the three most frequently occuring tissue engineering elements in the spinal cord injury. In terms of scientific output in the field of spinal cord injury mechanism research, the number of articles on stem cell-related research began to exceed that of biological scaffolds and growth factors in 2001 (7 articles campared to 1 and 5 articles), and this increase has continued. For over 20 years, the number of stem cell-related articles has consistently outnumbered those on biological scaffolds and growth factors, with the disparity widening over time. Since 2010, the number of articles on growth factor-related research has shown a downward trend, while the number of articles on biological scaffold-related research has increased steadily. Since 2012, the number of articles on biological scaffold-related research (33 articles) has consistently exceeded that of growth factors (22 articles). In the scientific output of clinical research in the field of spinal cord injury, the number of articles on stem cell-related research has gradually increased since 2002 (4 articles), and has consistently outnumbered those on biological scaffolds and growth factors. Since 2011, the number of articles on growth factor-related research has decreased, while the number of articles on biological scaffold-related research has increased. Since 2016, the number of articles on biological scaffold-related research (6 articles) has been higher than that of growth factors (3 articles). Before December 31, 2024, although the number of articles on stem cells was higher than those on growth factors and biological scaffolds (22 and 20 articles), the difference was far less significant than that for mechanism research (101 and 90 articles). The median scientific output of the three-element composite (48 articles) and its respective applications (37 stem cells articles, 33 growth factors articles, 17 biological scaffolds articles) in the field of tissue engineering all appeared in 2011. The scientific output of the three-element composite application in the field of spinal cord injury research was the highest in 2010 (9 articles). Taking 2010 as a boundary point, the research process can be divided into an early and a late stage. Early research focused on a single element, whereas late stage research turned to the composite application of all three elements. Related research results showed a rapid growth trend. Around 2010, the number of articles on the application of the three elements in the field of spinal cord injury was 2 445. The field entered a new period of rapid development around this time, with a growth rate of 9.15%, and has remained stable since then. Around 2010, the discovery and application of induced pluripotent stem cells also began to receive significant attention (496 articles), and related research has remained active ever since. The top five most influential researchers in the field of spinal cord injury neurorestoration were Dai JW (Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China), Gage FH (Solke Institute of Biology, USA), G?tz M (Biomedical Center of the University of Munich, Germany), Song HJ (Johns Hopkins University School of Medicine, USA), and Shoichet MS (University of Toronto, Canada). Notably, only Dai JW team has published clinical studies exhibiting a head effect in the field.Conclusions:Based on the core database of Web of Science, the development of spinal cord injury was explored. Basic research into biological scaffolds, stem cells and growth factors has developed rapidly, with stem cells and biological scaffold material research being particularly active. The three elements are gradually tending towards multi-strategy combined application. Although research objectives in spinal cord injury have advanced from exploring the basic research of the three elements to clinical transformation, the efficiency with which research results are transformed into clinical practice remains low.

Objective:To improve the understanding of the clinical manifestation of immunoglobulin G 4-related disease (IgG 4-RD) with neurological involvement. Methods:Patients presenting with neurological symptoms and biopsy-confirmed IgG 4-RD were enrolled between March 2014 and March 2024 from the Department of Neurology of Xuanwu Hospital of Capital Medical University. Medical record data of all patients were retrospectively reviewed, including clinical manifestations, laboratory findings, radiological results, pathology, treatments, and outcomes. RD were enrolled between March Results:Nine patients (five males, four females; median age at onset: 63 years) were included in the study. Neurological manifestations consisted of pachymeningitis in six cases, peripheral nerve involvement in two, and brain parenchyma involvement in one. Four patients displayed isolated neurologic symptoms. The most common clinical manifestations were headache and cranial nerve palsy, each involving five cases. Magnetic resonance imaging showed thickening and enhancement of the dura mater in the six patients with pachymeningitis. Four of these cases involved the posterior cranial fossa, 3 presented with an inflammatory pseudotumor, and 2 involved the spinal cord. Four patients with pachymeningitis had normal serum IgG 4 concentrations. Eight patients exhibited elevated serum C-reactive protein or erythrocyte sedimentation rates, with some also showing decreased complement C3 and C4 levels. Cerebrospinal fluid immunoglobulin was elevated in all nine cases. In all cases, histopathologic biopsy results showed extensive infiltration of lymphocytes and plasma cells, with the latter displaying IgG 4+abnormalities. All patients received glucocorticoid therapy, with six also receiving immunosuppressants. All patients were followed up for a median of 30 months, with outcomes including two complete remissions, five partial remissions, one unchanged condition, and one death. Six patients experienced a relapse. Conclusions:Isolated hypertrophic pachymeningitis is the most common manifestation of IgG 4-RD, often occurring in the absence of elevated serum IgG 4 levels. Peripheral nerve and brain parenchyma involvement can also be seen. Clinical manifestations are non-specific, and histopathologic biopsy is frequently required for diagnosis. Although the disease responds well to hormone treatment, recurrence is common. Early combined immunosuppressive therapy can improve prognosis.

The new cultural construction of high-quality development of public hospitals proposes a patient-oriented ap-proach.People with disabilities,represented by the hearing-impaired community,faces many difficulties in the process of seeking medical care,and their needs have not been adequately addressed.This inadequacy adversely affects the development of harmoni-ous doctor-patient relationships and the patient medical experience.This study takes the deaf assistance outpatient clinic,first es-tablished by Shanghai East Hospital as an example to elaborate the practice of cultural brand construction under the leadership of Party building.Medical social workers,healthcare professionals,and volunteers work together to build a cultural brand through institutional guarantees,detailed care,and the establishment of a full process service system.This is expected to provide refer-ences for the construction of hospital cultural brands..

Objective:To investigate the effect of astragalus polysaccharide(APS)on macrophage phagocytosis of P.aerugino-sa and its related mechanism.Methods:The effect of APS on the activity of macrophages was detected by CCK-8 assay.The effect of APS on macrophage phagocytosis related signal pathways were detected by Western blot.Gentamicin protection test and flow cytometry were employed to evaluate the effect of APS on macrophage phagocytosis of P.aeruginosa.Then the macrophages were pretreated with the inhibitors of TLR4,NF-κB,STAT3,MAPK and PI3K to assess the mechanism mediating APS on macrophage phagocytosis.Results:APS promotes the activity of macrophages,and significantly promoted the phagocytosis of P.aeruginosa by macrophages.Fur-thermore,macrophage phagocytosis of P.aeruginosa was significantly inhibited by TLR4 inhibitors(TAK242)and PI3K inhibitors(LY294002),but not affected by NF-κB,STAT3 and MAPK inhibitors.Conclusion:APS has no toxicity on macrophages,and can promote the phagocytosis of macrophages to P.aeruginosa,the underlying mechanism may be related to TLR4/PI3K pathway.

Objective To explore the application of graded nursing based on humanistic care in frail elderly patients with chronic obstructive pulmonary disease(COPD).Methods A total of 138 patients with COPD treated in Qinhuai Branch,The General Hospital of Eastern Theater Command from October 2020 to April 2023 were randomly assigned into two groups by a random number table,with 69 patients in each group.The control group received routine nursing care based on humanistic care,and the observation group were given routine nursing and graded nursing care according to the frailty scale.Clinical indicators,self-efficacy,treatment compliance and quality of life were compared between the two groups.Results After intervention,the partial pressure of carbon dioxide(PaCO2),partial pressure of oxygen(PaO2),blood oxygen saturation(SpO2),and the scores of self-decision-making,self-stress reduction and positive attitude of the two groups were improved,especially in the observation group(P<0.05).The compliance rate of observation group was higher than that of control group(97.10%vs.84.06%,P<0.05).The scores of vitality(VT),physical pain(BP),physiological function(RP),social function(SF),emotional function(RE),physiological function(PF),mental health(MH)and overall health(CH)in the observation group were higher than those in the control group(P<0.05).Conclusion The combined application of graded nursing based on frailty scale and humanistic care in COPD patients can effectively improve the quality of routine nursing,patient's self-efficacy,treatment compliance,illness status,and quality of life.

The new cultural construction of high-quality development of public hospitals proposes a patient-oriented ap-proach.People with disabilities,represented by the hearing-impaired community,faces many difficulties in the process of seeking medical care,and their needs have not been adequately addressed.This inadequacy adversely affects the development of harmoni-ous doctor-patient relationships and the patient medical experience.This study takes the deaf assistance outpatient clinic,first es-tablished by Shanghai East Hospital as an example to elaborate the practice of cultural brand construction under the leadership of Party building.Medical social workers,healthcare professionals,and volunteers work together to build a cultural brand through institutional guarantees,detailed care,and the establishment of a full process service system.This is expected to provide refer-ences for the construction of hospital cultural brands..

Objective:To improve the understanding of the clinical manifestation of immunoglobulin G 4-related disease (IgG 4-RD) with neurological involvement. Methods:Patients presenting with neurological symptoms and biopsy-confirmed IgG 4-RD were enrolled between March 2014 and March 2024 from the Department of Neurology of Xuanwu Hospital of Capital Medical University. Medical record data of all patients were retrospectively reviewed, including clinical manifestations, laboratory findings, radiological results, pathology, treatments, and outcomes. RD were enrolled between March Results:Nine patients (five males, four females; median age at onset: 63 years) were included in the study. Neurological manifestations consisted of pachymeningitis in six cases, peripheral nerve involvement in two, and brain parenchyma involvement in one. Four patients displayed isolated neurologic symptoms. The most common clinical manifestations were headache and cranial nerve palsy, each involving five cases. Magnetic resonance imaging showed thickening and enhancement of the dura mater in the six patients with pachymeningitis. Four of these cases involved the posterior cranial fossa, 3 presented with an inflammatory pseudotumor, and 2 involved the spinal cord. Four patients with pachymeningitis had normal serum IgG 4 concentrations. Eight patients exhibited elevated serum C-reactive protein or erythrocyte sedimentation rates, with some also showing decreased complement C3 and C4 levels. Cerebrospinal fluid immunoglobulin was elevated in all nine cases. In all cases, histopathologic biopsy results showed extensive infiltration of lymphocytes and plasma cells, with the latter displaying IgG 4+abnormalities. All patients received glucocorticoid therapy, with six also receiving immunosuppressants. All patients were followed up for a median of 30 months, with outcomes including two complete remissions, five partial remissions, one unchanged condition, and one death. Six patients experienced a relapse. Conclusions:Isolated hypertrophic pachymeningitis is the most common manifestation of IgG 4-RD, often occurring in the absence of elevated serum IgG 4 levels. Peripheral nerve and brain parenchyma involvement can also be seen. Clinical manifestations are non-specific, and histopathologic biopsy is frequently required for diagnosis. Although the disease responds well to hormone treatment, recurrence is common. Early combined immunosuppressive therapy can improve prognosis.

Objective:To investigate the effect of astragalus polysaccharide(APS)on macrophage phagocytosis of P.aerugino-sa and its related mechanism.Methods:The effect of APS on the activity of macrophages was detected by CCK-8 assay.The effect of APS on macrophage phagocytosis related signal pathways were detected by Western blot.Gentamicin protection test and flow cytometry were employed to evaluate the effect of APS on macrophage phagocytosis of P.aeruginosa.Then the macrophages were pretreated with the inhibitors of TLR4,NF-κB,STAT3,MAPK and PI3K to assess the mechanism mediating APS on macrophage phagocytosis.Results:APS promotes the activity of macrophages,and significantly promoted the phagocytosis of P.aeruginosa by macrophages.Fur-thermore,macrophage phagocytosis of P.aeruginosa was significantly inhibited by TLR4 inhibitors(TAK242)and PI3K inhibitors(LY294002),but not affected by NF-κB,STAT3 and MAPK inhibitors.Conclusion:APS has no toxicity on macrophages,and can promote the phagocytosis of macrophages to P.aeruginosa,the underlying mechanism may be related to TLR4/PI3K pathway.

Objective:To discuss the method for establishing the rat models of irritable bowel syndrome(IBS)by chronic water avoidance stress(WAS)method,and to evaluate its feasibility.Methods:Thirty male Wistar rats were randomly divided into control group(n=10)and model group(n=20).The rats in model group were induced by WAS method for 1 h everyday,lasting for 10 consecutive days;the rats in control group underwent no interventions.After modeling,the general conditions and body weights of the rats in two groups were observed and recorded.The elevated plus maze(EPM)test was used to detect the percentages of the number of open arm entries(OE)and the time spent in open arms(OT)of the rats in two groups;the abdominal withdrawal reflex(AWR)test was used to assess the visceral sensitivity of the rats in two groups;electrocardiography was used to detect the heart rate variability(HRV)of the rats in two groups;electromyography(EMG)of the external oblique muscle was used to detect the colorectal pain sensitivity thresholds of the rats in two groups;multi-channel physiological signal recorder was used to monitor the slow wave frequency of the colon of the rats in two groups.Results:There were no death rats in both groups during the modeling period.After modeling,the rats in model group exhibited poor mental status,reduced spontaneous activity,hypoactivity,disordered and dull fur,irritability,and unclean anal areas;whereas,the rats in control group showed no significant changes in the mental state,spontaneous activity,fur,and perianal area.Compared with control group,the body weight of the rats in model group was significantly decreased(P<0.05).The EPM test results showed that compared with control group,the OE percentage and OT percentage of the rats in model group were significantly decreased(P<0.01).The AWR test results showed that 12 rats in model group scored≥3 points,indicating that the successful rate in creating the visceral pain models was 60%.Compared with control group,the low frequency(LF)signals and the ratio of LF/high frequency(HF)of the rats in model group were significantly increased(P<0.01),and the HF was significantly decreased(P<0.05).The EMG results showed that compared with control group,the coloretal pain sensitivity threshold of the colon of the rats in model group was significantly decreased(P<0.01),and the slow wave frequency of the colon was significantly increased(P<0.01).Conclusion:The WAS method for establishing the rat model of IBS effectively demonstrates the changes in behavior and mental state,increased the visceral sensitivity,accelerated colonic slow wave frequency,and autonomic nervous system imbalance;the WAS method can serve as an effective modeling approach for observing and evaluating the related drugs and interventions on treatment of IBS.