[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.

Endometriosis （EMT） is a common disease with frequent occurrence and difficult to be cured in modern clinical practice of obstetrics and gynaecology. It is characterized by progressively worsening dysmenorrhoea， pelvic mass， and infertility. The incidence of EMT is growing and increasingly younger patients are diagnosed with this disease， which poses a serious threat to the reproductive and psychological health of women of childbearing age and adolescent females. However， the pathogenesis of EMT is still not completely clear， and the disease has a long course. Therefore， developing new therapies is an urgent clinical problem to be solved. Great progress has been achieved in the treatment of EMT with traditional Chinese medicine （TCM）， while the underlying mechanism remains in exploration. Programmed cell death （PCD） is a cell death mode mediated by a variety of bio-molecules with specific signaling cascades. The known PCD processes include apoptosis， pyroptosis， autophagy， ferroptosis， and cuproptosis， which all play a pivotal role in the development of EMT. Researchers have made achievements in the treatment of EMT with TCM， which regulates PCD via multiple pathways， routes， targets， and mechanisms. However， the progress in the regulation of PCD in the treatment of EMT with TCM remains to be reviewed. This paper reviews the research progress in the treatment of EMT with TCM from five PCD processes （apoptosis， pyroptosis， autophagy， ferroptosis， and cuproptosis）， with the aim of providing a theoretical basis for the clinical prevention and treatment of EMT.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

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 explore the relationships of vitamin D and oxidized low-density lipoprotein(ox-LDL)with infertility in patients with polycystic ovary syndrome(PCOS)based on restricted cubic spline models.Methods A total of 150 PCOS patients were selected as the study subjects and followed up for at least 1 year.They were divided into infertile group and non-infertile group according to whether they were infertile.A Logistic regression model was used to analyze the influencing factors of infertility in PCOS patients.Furthermore,the relationships of 1,25-dihydroxyvitamin D3[1,25-(OH)2D3]and ox-LDL with infertility in PCOS patients,as well as their interactive effects on infertility in PCOS patients were analyzed.A restricted cubic spline model was used to analyze the non-linear relationships between 1,25-(OH)2D3,ox-LDL,and infertility in PCOS patients.Results Among 150 PCOS patients,78 were not pregnant,resulting in an infertility rate of 52.00％(78/150).Multivariate Logistic regression analysis showed that the severity of PCOS,body mass index,age,1,25-(OH)2D3,and ox-LDL were all independent influencing factors for infertility in PCOS patients(P＜0.05).After adjusting for confounding factors,1,25-(OH)2D3 and ox-LDL were still associated with the risk of in-fertility in PCOS patients(P＜0.05).Restricted cubic spline model analysis revealed non-linear rela-tionships between 1,25-(OH)2D3,ox-LDL,and the risk of infertility in PCOS patients(P＜0.05).When the serum 1,25-(OH)2D3 level was＜35.70 nmol/L,it was negatively correlated with the risk of infertility in PCOS patients(P＜0.05).When the serum ox-LDL level was ≥381.00 μg/L,it was positively correlated with the risk of infertility in PCOS patients(P＜0.05).Interactive effect analysis showed that 1,25-(OH)2D3 and ox-LDL had antagonistic effects on infertility in PCOS pa-tients(P＜0.05).Conclusion Decreased serum 1,25-(OH)2D3 levels and increased ox-LDL levels in PCOS patients can significantly increase the risk of infertility.Moreover,there is a non-lin-ear dose-response relationship and an antagonistic interactive effect between them,suggesting that regulating vitamin D and oxidative stress levels may be an important strategy for improving the fertili-ty outcomes of PCOS patients.

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 explore the impact of previous cytomegalovirus (CMV), herpes simplex virus (HSV), and rubella virus (RV) infection on pregnancy outcomes in infertile women undergoing the first in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) treatment. Methods:A retrospective cohort study was conducted to analyze the clinical data of women who underwent IVF/ICSI-ET for the first time at the Reproductive Medicine Center, the First Affiliated Hospital of Zhengzhou University from December 2017 to December 2022. The patients were divided into CMV-IgG (+) group ( n=154), RV-IgG (+) group ( n=86), HSV-IgG (+) group ( n=93) and IgG all-negative group ( n=172). The pregnancy outcomes of the patients in the virus-only infection group and the IgG all-negative group were compared. Patients who were previously co-infected with CMV and HSV were classified as the CMV+HSV-IgG (+) group ( n=344), and the pregnancy outcomes of patients with previous CMV and HSV co-infection and those with infection alone were further compared. Results:The two pronuclei (2PN) fertilization rate [63.90% (1 195/1 870)], the clinical pregnancy rate [51.30% (79/154)], and the live birth rate [45.45% (70/154)] of the CMV-IgG (+) group were significantly lower than those of the IgG completely negative group [68.68% (1 469/2 139), P=0.001; 68.60% (118/172), P=0.001; 61.05% (105/172), P=0.005]. The 2PN fertilization rate [61.62% (729/1 183)], the clinical pregnancy rate [50.54% (47/93)], and the live birth rate [43.01% (40/93)] of the HSV-IgG (+) group were significantly lower than those of the IgG completely negative group [68.68% (1 469/2 139), P=0.001; 68.60% (118/172), P=0.004; 61.05% (105/172), P=0.005]. There were no statistical differences in the 2PN fertilization rate, the clinical pregnancy rate, and the live birth rate between the RV-IgG (+) group and the IgG completely negative group (all P>0.05). Compared with the IgG completely negative group, there were no significant differences in the risk of complications such as gestational diabetes, hypertensive disorders of pregnancy and neonatal outcomes in the CMV-IgG (+) group, RV-IgG (+) group, and HSV-IgG (+) group (all P>0.05). Multivariate logistic regression analysis showed that CMV-IgG (+) ( OR=0.453, 95% CI: 0.280-0.734, P=0.001; OR=0.515, 95% CI: 0.321-0.825, P=0.006), HSV-IgG (+) ( OR=0.425, 95% CI: 0.245-0.738, P=0.002; OR=0.447, 95% CI: 0.259-0.771, P=0.004) and CMV+HSV-IgG (+) ( OR=0.491, 95% CI: 0.329-0.733, P=0.001; OR=0.528, 95% CI: 0.357-0.780, P=0.001) were all independent influencing factors of patients' clinical pregnancy and live birth. There were no statistical differences in the clinical outcomes between the previous CMV and HSV co-infection group and the single infection group ( P>0.05). Conclusion:Previous CMV or HSV infection alone reduced the fertilization rate, the clinical pregnancy rate and the live birth rate of patients undergoing IVF/ICSI-ET treatment, but had no significant impact on pregnancy complications and neonatal outcomes. Pregnancy outcomes of patients with previous CMV and HSV co-infection were similar to those with infection alone.