[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。

To address the constrains imposed by insufficient hydrogen peroxide (H2O2) and high glutathione (GSH) expression in tumor cells on the efficacy of chemodynamic therapy (CDT), zeolitic imidazolate framework-8 (ZIF-8) loaded with disulfiram (DSF) and 3-amino-1,2,4-triazole (3-AT) was synthesized via a one-pot approach. Subsequently, hyaluronic acid (HA)-modified cupric peroxide (CuO2) was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH (3-AT/DSF@ZIF-8@CuO2-HA). This nanoplatform disrupts the intratumoral H2O2 homeostasis, depletes GSH, and synchronously delivers DSF and Cu2+ via cascade catalysis, thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy. The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility. Its particle size and Zeta potential were 196.5 nm and −19.5 mV, respectively. It possessed a microporous structure with a specific surface area of 81.8600 m2/g, and demonstrated efficient loading capacity for DSF and 3-AT, achieving drug loading efficiencies of 5.91% and 45.07%, respectively. Moreover, ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions. In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration- and incubation time-dependent manner. Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells. Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells. DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species (ROS) generation, thereby enhancing CDT efficacy. Live/dead staining experiments showed that ADZCH efficiently induced apoptosis, with the proportion of dead cells reaching 94.74%, demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.

Objective: To explore the temporal variation in physical health status among college students, analyze the correlation and dose response relationship between body mass index (BMI) and physical fitness indicators, so as to provide a scientific basis for physical health intervention among college students in universities. Methods: A total of 4 910 freshmen in the 2021 grade at Xi an Jiaotong University were selected. The BMI and changes in five physical fitness indicators (50 meter run, endurance run, standing long jump, sit and reach, and pull up or 1 minute sit up) were continuously assessed during follow up evaluations from 2021 to 2024. One way analysis of variance, generalized estimating equation (GEE), and other statistical methods were used to analyze the trends in temporal variation among the physical fitness indicators as well as the correlation characteristics and dose response relationship between BMI and physical fitness. Results: In 2021 the overweight and obesity rates among male freshmen were 20.36 % and 8.62%, respectively, and 12.91% and 2.91% among female freshman, respectively. From 2021 to 2024 the BMI of male and female students showed an upward trend with a significant increase( F =87.29,3.69,both P <0.05). The physical fitness indicators for both male and female students, including the 50 meter run, standing long jump, pull up and 1 minute sit up, first increased and then decreased, the endurance run performance decreased, and the sit and reach performance first decreased and then increased. The GEE model showed that BMI was negatively correlated with the performance of standing long jump, pullup/1 minute sit up, and sit and reach in both male and female students（ β =-1.72，-0.34，-0.15；-0.94，-0.26，-0.12）, and positively correlated with the time of 50 meter run and endurance run（ β =0.05，3.16；0.03，1.86）（all P ＜0.05）. The increase in BMI was associated with physical fitness decline in a non linear dose response relationship, while the sit and reach performance reached a peak at a BMI of approximately 22 kg/m 2, then decreased with the further increase in BMI. Conclusions A significant negative correlation is demonstrated between BMI and physical fitness indicators and male students are more sensitive to changes in BMI. College students should be guided to actively manage their weight and attach importance to physical exercise to improve their physical health.

Objective:To explore the prognosis and influencing factors of early-onset neonatal sepsis (EONS), and provide the guidance for early clinical prevention and treatment.Methods:The clinical data of 147 children with EONS in Shijiazhuang Maternal and Child Health Hospital from January 2019 to December 2023 were retrospectively analyzed. The baseline data and prognosis data (good prognosis and poor prognosis) were recorded. Multivariate Logistic regression analysis was used to analyze the risk factors of poor prognosis in children with EONS. R3.5.3 software package was used to build a nomogram model for predicting poor prognosis in children with EONS, and the rms package was used to calculate the consistency index ( C- index), and Bootstrap self-sampling was used for internal verification. Results:Among the 147 children with EONS, 41 children (27.89%) had poor prognosis, and 106 children (72.11%) had good prognosis. The incidence of thrombocytopenia, incidence of bacterial meningitis, procalcitonin and lactate in children with poor prognosis were significantly higher than those in children with good prognosis: 68.29% (28/41) vs. 17.92% (19/106), 43.9% (18/41) vs. 1.89% (2/106), (70.36 ± 13.45) ng/L vs. (42.76 ± 10.37) ng/L and (6.18 ± 2.05) mmol/L vs. (4.22 ± 1.05) mmol/L, and there were statistical differences ( P<0.01); there were no statistical difference in gender composition, gestational age, birth weight, 1 min Apgar score, delivery mode, white blood cell, C-reactive protein, creatinine and the incidences of placental abruption, amniotic fluid contamination, maternal infection, necrotizing enterocolitis between the two groups ( P>0.05). Multivariate Logistic analysis result showed that thrombocytopenia, bacterial meningitis, high procalcitonin and high lactate were the independent risk factors for poor prognosis in children with EONS ( OR = 9.595, 22.657, 1.213 and 2.614; 95% CI 1.094 to 20.055, 1.833 to 41.328, 0.745 to 0.937 and 0.990 to 1.209; P<0.05 or <0.01). A nomogram model was constructed to predict poor prognosis in children with EONS, using thrombocytopenia, bacterial meningitis, procalcitonin and lactate as predictive factors. The nomogram model predicted that the correction curve for poor prognosis in children with EONS tended towards the ideal curve ( C- index = 0.987, 95% CI 0.975 to 0.998). Conclusions:The children with EONS have a higher risk of adverse prognosis, which may be related to their comorbidities with thrombocytopenia, bacterial meningitis, high procalcitonin and high lactate at diagnosis. The nomogram model established based on the indexes has a good predictive effect on the disease prognosis.

Objectives:This study aims to investigate the expression changes of transient receptor potential vanilloid type 1 (TRPV1) channel and inflammatory factors in the peripheral blood of patients with schizophrenia, and to evaluate their potential value for diagnostic prediction.Methods:This cross-sectional study was conducted at Renmin Hospital of Wuhan University from September 2023 to June 2024. A total of 35 patients with schizophrenia (patient group) from the outpatient/inpatient departments and 35 age-and sex-matched healthy individuals (control group) were recruited. Psychiatric symptoms and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The between-group comparisons of the total scores of these two instruments were calculated using independent samples t-tests. Fasting peripheral blood samples were collected from all participants. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated for subsequent analysis. TRPV1 protein expression was quantified by Western blotting, while inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10), were measured using enzyme-linked immunosorbent assay (ELISA). The between-group differences in TRPV1 and inflammatory cytokines were analyzed using the analysis of covariance (ANCOVA), controlling for age and sex. Pearson correlation analysis was employed to examine relationships between continuous variables, controlling for years of education, age, and sex. The diagnostic performance of TRPV1 and inflammatory cytokines for schizophrenia was assessed using receiver operating characteristic (ROC) curve analysis. Results:Significant between-group differences were observed in BACS total and subscale scores ( t=2.57-9.72, all P<0.01). Compared with the control group, the patient group exhibits significantly decreased expression of TRPV1, IL-4, and IL-10 ( t=6.78, 2.75, 2.53, all P<0.01), increased expression of TNF-α, IL-2, and IL-6 ( t=4.08, 2.64, 2.63, all P<0.01), and an increased IL-6/IL-10 ratio ( t=3.18, P<0.01). Correlation analyses revealed that in the patient group, the TRPV1 expression level was negatively correlated with levels of TNF-α and IL-6, and positively correlated with levels of IL-4 and IL-10 ( r=-0.589, -0.234, 0.341, 0.293, all P<0.05). In the patient group, the TRPV1 expression level was negatively correlated with the negative symptom score of PANSS ( r=-0.299, P<0.05), and the IL-6 level was positively correlated with the negative symptom score, the general pathology score, and the total score of PANSS ( r=0.387, 0.356, 0.321, all P<0.05). The TRPV1 level was positively correlated with the total score of BACS in both the control group and the patient group ( r=0.144, 0.828, all P<0.01). The IL-6/IL-10 ratio was positively correlated with the total score of PANSS and negatively correlated with the total score of BACS in the patient group ( r=0.623, -0.333, all P<0.05). The area under the ROC curve for the combination of TRPV1 level and IL-6/IL-10 ratio was 0.98 (95% confidence interval=0.96 to 1.00). Conclusions:Patients with schizophrenia exhibit reduced expression levels of TRPV1 along with an imbalanced inflammatory response. The combined assessment of TRPV1 level and IL-6/IL-10 ratio has demonstrated a high predictive and diagnostic value for schizophrenia.

Objective To analyze the serum 25-hydroxy vitamin D[25(OH)D]levels and vitamin D nutri-tional status of 0-14 years old children in Hangzhou,and to provide scientific basis for the prevention of vita-min D deficiency.Methods A total of 26 225 healthy children aged 0 to 14 who were tested in Hangzhou Dian Medical Diagnosis Center from January 1,2021 to December 31,2023 were selected as the study objects.The 25(OH)D levels were detected by direct chemiluminescence method,and the 25(OH)D levels and vitamin D nutritional status of children with different genders,ages and seasons were analyzed and compared.Results The level of 25(OH)D in girls was slightly higher than that in boys,and the difference was statisti-cally significant(P＜0.05).With the increase of age,the level of 25(OH)D continued to decline,and the pro-portion of vitamin D deficiency and vitamin D insufficiency gradually increased.The level of 25(OH)D was the highest in children＜3 years old and the lowest in children 10-14 years old.There was statistical significance in the proportion of vitamin D nutritional status between boys and girls aged 10 to 14(P＜0.05).In the four seasons,children's 25(OH)D level is the highest in spring and the lowest in summer.The difference of 25(OH)D level and vitamin D nutritional status in different seasons was statistically significant(P＜0.05).The proportion of vitamin D deficiency and vitamin D insufficiency in winter was higher than that in other seasons,and the difference was statistically significant(P＜0.05).Conclusion The nutritional status of vitamin D in 0-14 year old children in Hangzhou is good,but the importance of vitamin D supplementation for children should not be ignored,and active publicity and education should be carried out to prevent vitamin D deficiency.

Objective:To establish a risk prediction model based on least absolute shrinkage and selection operator (LASSO) regression for procalcitonin (PCT), milk fat globule-epidermal growth factor 8 (MFG-E8) and CXC chemokine ligand 9 (CXCL9) in elderly patients with liver cancer after transcatheter arterial chemoembolization (TACE) .Methods:A total of 150 elderly patients with liver cancer who underwent TACE treatment in Shishi City Hospital, Fujian Province and 910th Hospital of the Chinese People's Liberation Army Joint Logistic Support Force from August 2020 to August 2023 were selected as the study subjects. Patients with infection after TACE were included in the infected group and those without infection were included in the non-infected group according to whether the patients had infection during the postoperative hospitalization. The baseline data of patients were collected and compared. LASSO regression was used to screen the factors that may affect the infection after TACE in elderly patients with liver cancer and binary logistic regression analysis was performed. According to the results of regression analysis, a nomogram model was constructed based on the regression analysis results and the nomogram was internally validated using Bootstrap and receiver operator characteristic (ROC) curves.Results:There were 18 cases of infection in 150 elderly patients with liver cancer after TACE, with an incidence of 12.00%. There were statistically significant differences in focal rupture and bleeding ( χ2=5.92, P=0.015), ascites ( χ2=6.70, P=0.010), skin or mucosal damage ( χ2=6.67, P=0.010) between the infected group ( n=18) and the non-infected group ( n=132). The levels of serum PCT [ (1.17±0.32 ) μg/L vs. (0.91±0.14) μg/L], MFG-E8 [ (194.29±45.85) pg/ml vs. (158.76±28.63) pg/ml] and CXCL9 [ (948.49±52.38) pg/ml vs. (886.05±50.07) pg/ml] were higher than those in the non-infected group, with statistically significant differences ( t=4.13, P<0.001; t=4.55, P<0.001; t=4.94, P<0.001). Four factors related to infection after TACE intervention in patients with liver cancer were finally selected by LASSO regression model, skin or mucosal damage, PCT, MFG-E8, CXCL9 levels. Binary logistic regression analysis showed that skin or mucosal damage ( OR=13.48, 95% CI: 1.29-140.47, P=0.030), high levels of serum PCT ( OR=1.13, 95% CI: 1.05-1.22, P=0.001), MFG-E8 ( OR=1.04, 95% CI: 1.01-1.07, P=0.003), CXCL9 ( OR=1.05, 95% CI: 1.02-1.08, P=0.001) were risk factors for infection after TACE in elderly patients with liver cancer. Based on skin or mucosa damage, PCT, MFG-E8 and CXCL9, a nomogram prediction model for postoperative infection in elderly patients with liver cancer after TACE intervention was established. Calibration curve showed that the C-index of postoperative infection predicted by the nomogram model in elderly patients with liver cancer after TACE intervention was 0.939, indicating the model had good discrimination. ROC curve analysis showed that the area under the curve (AUC) predicted by the nomogram model for infection after TACE intervention in elderly patients with liver cancer was 0.960 (95% CI: 0.926-0.995, P<0.001), which had certain predictive value. The specificity, sensitivity and Youden index were 0.864, 0.944 and 0.808, respectively. Conclusions:Skin or mucosal damage, high levels of serum PCT, CXCL9 and MFG-E8 are closely related to postoperative infection in elderly patients with liver cancer after TACE, and the prediction model constructed based on this has better predictive performance for postoperative infection.

Objective To explore the efficacy of Yishen Yangyin Gujing Prescription[derived from Zuogui Wan(Bolus for Replenishing Kidney-Yin)]for the treatment of diabetic nephropathy in type 2 diabetes mellitus(T2DM)with qi and yin deficiency syndrome,and to observe its effects on inflammatory responses,pancreatic β-cell function and renal function.Methods A total of 162 T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome who admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from May 2020 to July 2023 were randomly divided into an observation group and a control group according to the random number table method,with 81 cases in each group.The control group was given conventional western medicine treatment for lowering blood pressure and renal protection,while the observation group was treated with Yishen Yangyin Gujing Prescription on the basis of treatment for the control group.The course of treatment for the two groups covered 12 weeks.Before and after the treatment,the changes in the outcomes of the two groups were observed,and the outcomes included the total scores of traditional Chinese medicine(TCM)syndrome,insulin sensitivity index,insulin secretion index,24-h urine total protein quantification(24hUTP),and serum levels of glycosylated hemoglobin(HbA1c),fasting insulin(FINS),fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),transforming growth factor β1(TGF-β1),NLRP3 inflammasome,interleukin 6(IL-6),superoxide dismutase(SOD)and sphingosine-1-phosphate(S1P).After treatment,the clinical efficacy of the two groups of patients was compared.Results(1)After 12-week treatment,the total effective rate of the observation group was 93.83%(76/81),and that of the control group was 83.95%(68/81).The intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group(χ2=9.163,P<0.05).(2)After treatment,the insulin sensitivity index and insulin secretion index in the two groups of patients were increased(P<0.05)and the total scores of TCM syndromes were decreased(P<0.05)when compared with those before treatment,and the increase of insulin sensitivity index and insulin secretion index as well as the decrease of the total scores of TCM syndrome in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,the serum levels of HbA1c,FINS,FBG,SCr,BUN and 24hUTP in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of the above indicators in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the serum TGF-β1,IL-6,and NLRP3 inflammasome levels in the two groups of patients were decreased(P<0.05)and the serum S1P and SOD levels were increased(P<0.05)when compared with those before treatment,and the decrease of serum TGF-β1,IL-6,and NLRP3 inflammasome levels as well as the increase of serum S1P and SOD levels in the observation group was significantly superior to that in the control group(P<0.05).Conclusion For T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome,the combined use of western medicine and Yishen Yangyin Gujing Prescription treatment is helpful to alleviate inflammatory response,improve the function of pancreatic β-cells,regulate the blood glucose level,improve renal function,and enhance the clinical efficacy.

Objective:To observe any effect of oscillating positive expiratory pressure training on the airway clearing ability of postoperative esophageal cancer patients after neoadjuvant chemotherapy.Methods:Forty postoperative esophageal cancer patients undergoing neoadjuvant chemotherapy were enrolled and randomized into a control group and an experimental group, each of 20. Both groups received conventional postoperative rehabilitation starting on the first postoperative day, while the experimental group additionally underwent oscillating positive expiratory pressure training (3 sets/day, 30 breaths/set) for five consecutive days. Peak cough flow was measured using a peak flow meter before and 1, 3 and 5 days after the operation. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) were also measured on the 5th day after the operation using spirometry. Any postoperative pulmonary complications were recorded.Results:On the 1st day after the operation, peak cough flow had decreased significantly in both groups compared to preoperative levels. However, it had increased significantly on days 3 and 5 in both groups, with the average increase in the experimental group significantly greater than in the control group. On day 5 the average FEV1, forced vital capacity and PEF in both groups were significantly lower than the preoperative values, while the experimental group demonstrated significantly higher average FEV1s (2.22±0.51L) and PEFs (5.09±1.26L/s) compared to the control group.Conclusions:Early postoperative oscillating positive expiratory pressure training can improve the peak cough flow and airway clearing ability of esophageal cancer patients after neoadjuvant chemotherapy, promoting the recovery of their lung function.

The chest wall is one of the most common sites of local recurrence after mastectomy. Radiation therapy has been proven to significantly reduce local recurrence and improve survival in breast cancer patients. In postmastectomy radiation therapy (PMRT), the dose build-up effects of high-energy radiation result in lower doses on the skin surface of the affected chest wall. To increase the skin dose, tissue compensators (boluses) need to be applied to the skin surface of the affected chest wall. This review primarily summarizes the indications, materials, thickness, and frequency of boluses used in PMRT, serving as a reference for clinical practice.