[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 discuss the correlation of International Society of Urological Pathology (ISUP) pathological grading with 18F-prostate specific membrane antigen (PSMA)-1007 positron emission tomography-computed tomography (PET/CT) parameters and serum total prostate specific antigen (tPSA) in prostate cancer, and assess the clinical value of PET/CT combined with tPSA in predicting the ISUP pathological grade of prostate cancer. Methods:The correlation of ISUP pathological grade with primary parameters of PET/CT images and serum tPSA of 117 patients diagnosed with prostate cancer at Shanxi Cancer Hospital from August 2018 to February 2023 and taken 18F-PSMA-1007 PET/CT imaging were retrospectively analyzed. Univariate and multivariate logistic regressions were used to identify the independent influencing factors for ISUP pathological grading of prostate cancer. The receiver operating characteristic (ROC) curves were used to predict the efficacy between the high and low ISUP grades for prostate cancer. Results:Of the 117 patients, 20 were in ISUP Group 1, 25 in Group 2, 18 in Group 3, 32 in Group 4, and 22 in Group 5. Of these, 63 were in the low-grade group (Groups 1-3) and 54 were in the high-grade group (Groups 4-5). The tumor long diameter was 3.10 (2.05, 4.25) cm, the prostate volume was 40.11 (33.13, 51.85) cm 3, the serum tPSA was 19.71 (12.25, 42.83) ng/ml, the prostate specific antigen density (PSAD) was 0.51 (0.31, 1.01) ng·ml -1·cm -3, the maximum standard uptake value of the lesion (SUVmax) was 15.24 (10.87, 22.03), and the tumor/spleen uptake ratio (TSR) was 1.61 (1.08, 2.15) in the 117 patients. The correlation analysis displayed that the SUVmax, TSR, and tPSA were positively correlated with ISUP groups ( r=0.640, 0.619, and 0.500, P＜0.01). The differences among SUVmax, TSR, long diameter, tPSA, and PSAD were statistically significant when compared among the five ISUP groups ( H=48.98, 45.63, 26.82, 33.95, and 23.81, P＜0.001). The differencesin serum tPSA ( z=5.19), PSAD ( z=4.64), long diameter ( z=3.19), SUVmax ( z=5.57), and TSR ( z=5.53) of the patients between the low-grade group and the high-grade group were statistically significant ( P＜0.01). In multivariate analysis, TSR ( OR=4.172, 95% CI: 2.095-8.308, P＜0.001) and the serum tPSA ( OR=1.042, 95% CI: 1.014-1.070, P＜0.01) were independent influencing factors for ISUP grades. ROC analysis revealed that the area under the curve for the 18F-PSMA-1007 PET/CT parameters SUVmax and TSR to predict low- or high-grade ISUP for prostate cancer was 0.800 (95% CI: 0.717-0.883) and 0.797 (95% CI: 0.713-0.881), respectively. Among the 70 patients who underwent radical prostatectomy, the postoperative recurrence rate of high-grade ISUP patients was higher than that of low-grade patients (54.8% and 25.6%, χ 2=6.21, P＜0.05). Conclusions:18F-PSMA-1007 PET/CT has good application in predicting ISUP grading of prostate cancer. TSR and the serum tPSA are independent predictors for the pathological grade.

Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

Objective To explore the latent profile analysis of oral frailty in elderly patients with multiple chronic conditions and to analyze the influencing factors of different potential profiles in order to provide a theoretical basis for constructing clinical intervention programs.Methods Convenience sampling method was used to select elderly patients with multiple chronic conditions in a tertiary hospital in Hefei City from July to December 2024 as the survey subjects.General information questionnaire,the Chinese version of the Oral Frailty Index-8,Mini-Nutritional Assessment Short-Form,Consumer Health Activation Index and Family APGAR Index Questionnaire were used to conduct the survey,and multivariate logistic regression was used to analyze the influencing factors.Results A total of 418 elderly patients with multiple chronic conditions were included,with a total oral frailty score of(7.21±2.83).Oral frailty in elderly patients with multiple chronic conditions can be classified into 3 potential profiles,namely severe oral frailty-low oral functioning group(60.53％),moderate oral frailty-high social behaviors group(8.85％),mild oral frailty-high oral health behavior group(30.62％).Age,family care,type of chronic disease,type of oral medication,and consumer health activation index were influential factors for different potential profiles(P＜0.05).Conclusion The oral frailty in elderly patients with multiple chronic conditions was heterogeneous.Caregivers should focus on the severe oral frailty-low oral functioning group and the moderate oral frailty-high social behavior group,and develop targeted interventions according to the patients'different profile characteristics and influencing factors to prevent and delay the occurrence of oral frailty.

Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

In recent years, mesenchymal stem cell-derived exosomes (MSC-EXO) have garnered increasing attention in the field of stomatology and have become an established research area in biomedical research. This article reviews the engineering of exosomes derived from mesenchymal stem cells and their application in the field of stomatology, in order to provide new ideas for the development of stomatology. Exosomes are nanoscale membrane vesicles secreted by cells and contain a variety of proteins, RNAs, lipids, and other biomolecules. They are transported through the circulatory system and can interact with other cells to regulate their biological behavior and participate in a variety of physiological and pathological processes. In the treatment of oral diseases, exosomes have shown great potential due to their natural biological activity and versatility. However, studies have found that relying solely on the function of natural exosomes may not fully meet the complex clinical requirements. Therefore, the concept of engineered exosomes has emerged. Engineered exosomes can be modified by bioengineering technology to enhance their targeting, allowing them to reach the lesion site more accurately. At the same time, engineered exosomes can also be surface modified or loaded internally to carry specific therapeutic molecules, such as drugs, gene editing tools or signaling molecules to improve the therapeutic effect. In addition, this engineered treatment can also confer greater stability to exosomes, making them better able to resist clearance by the immune system when circulating in the body, extending their half-life, and improving the effectiveness of treatment. Although engineered exosomes have attracted extensive attention in the fields of stomatology and other fields, their application is still mainly in the stage of basic research. To promote the clinical application of engineered exosomes, it is necessary to provide more sufficient evidence of biocompatibility and clarify their therapeutic effect and mechanism.

Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model， this paper used multiple databases to search for the keywords "heart and spleen deficiency"， "insomnia"， "sleepless"， "disease syndrome-combined animal model"， "model evaluation"， etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment， modeling factors， syndrome model， disease model， macro characterization & macro characterization evaluation scale， micro indicators， etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method， the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease， and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation， which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine （TCM） syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome， along the specific related ideas of "prescription and syndrome， treatment principle and selection of prescription， treatment principle and selection of acupoints， as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice， so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.

Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model， this paper used multiple databases to search for the keywords "heart and spleen deficiency"， "insomnia"， "sleepless"， "disease syndrome-combined animal model"， "model evaluation"， etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment， modeling factors， syndrome model， disease model， macro characterization & macro characterization evaluation scale， micro indicators， etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method， the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease， and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation， which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine （TCM） syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome， along the specific related ideas of "prescription and syndrome， treatment principle and selection of prescription， treatment principle and selection of acupoints， as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice， so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.

Objective To discuss the effect of interleukin-17A(IL-17A)and transforming growth factor-β1(TGF-β1)on the benign tracheal stenosis after tracheal injury in experimental dogs.Methods The trachea stenosis model of healthy Beagle dogs was established by burning the middle part of trachea with electric snare under bronchoscopy guidance.A total of 21 dogs were divided into normal group(n=3,receiving normal feeding),molding group(n=12,after airway modeling every 3 dogs were sacrificed each week for 4 weeks),IL-17A suppression group(n=3,receiving Secukinumab after airway modeling),and IL-17A inhibitor+TGF-β1 inhibitor group(n=3,receiving Secukinumab and SB43154 after airway modeling).Bronchoscopy and CT scan were performed once a week,and the stenosis degree was calculated.RT-qPCR,immunohistochemistry,and HE staining of the obtained tracheal tissues were performed.Results Within 1-4 weeks after molding,in module-making dogs the degree of stenosis of the injured trachea gradually increased,and the expressions of ECM-related proteins,TGF-β1 and IL-17A were up-regulated.After treatment with IL-17A inhibitors,the inflammatory infiltration and granulation tissue hyperplasia were reduced and the early tracheal stenosis was improved(P＜0.05).The combination use of IL-17A inhibitor and TGF-β1 inhibitor had a better remission effect(P＜0.05).Conclusion IL-17A and TGF-β1 may synergistically affect the formation of tracheal stenosis.

Objective A scoping review of studies on pulmonary prehabilitation in cardiac surgery patients was conducted to provide evidence support for the construction of a preoperative pulmonary rehabilitation program for cardiac surgery patients that suitable for China's national conditions.Methods In accordance with the scope review's research methodologies,databases including PubMed,Embase,Web of Science,CINAHL,CNKI and Wanfang were searched by the computer for relevant studies.The deadline for retrieval is from the establishment of databases to June,2024.The included literature was systematically analyzed.Results 26 articles were finally included.Among them,4 were quasi-experiment studies,while the other 22 were randomized controlled trials.Forms of the intervention included comprehensive breathing exercises,inspiratory muscle training,positive expiratory pressure,incentive spirometer training and balloon blowing training.The intervention initiation ranged from 10 weeks to 1 day preoperatively;the outcome measures included postoperative pulmonary complications,lung function metrics,the 6-Minute Walk Test,duration of mechanical ventilation,length of hospital stay,patient-reported outcomes and so on.Conclusion There remains a deficiency in standardized protocols for preoperative pulmonary rehabilitation training among patients undergoing cardiac surgery.High-quality studies should be conducted,and intervention strategies for pulmonary prehabilitation in cardiac surgery patients should be optimized and a unified evaluation standard system should be established.