BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.

[摘 要] 目的：探究连翘苷（PHN）调节高迁移率族蛋白B1（HMGB1）/晚期糖基化终产物受体（RAGE）信号通路对胶质瘤U251细胞增殖、侵袭及上皮间质转化（EMT）的影响。方法：将人胶质瘤U251细胞分为PHN-0组（0 µmol/L PHN处理）、PHN低、中和高剂量组（PHN-50、PHN-100、PHN-200组，分别用50、100和200 µmol/L PHN处理）、PHN + pcDNA-NC组（转染pcDNA-NC质粒后200 µmol/L PHN处理）和PHN + HMGB1组（转染过表达HMGB1质粒后200 µmol/L PHN处理）。CCK-8法和克隆形成实验检测各组细胞的增殖能力，流式细胞术检测各组细胞的凋亡水平，Transwell实验检测各组细胞的迁移和侵袭能力，ELISA检测各组细胞分泌IL-8水平，免疫荧光法检测各组细胞中神经钙黏素（N-cadherin）和上皮钙黏素（E-cadherin）阳性率，WB法检测各组细胞中Toll样受体4（TLR4）、核因子-κB（NF-κB）、HMGB1、RAGE、N-cadherin、E-cadherin、细胞周期蛋白D1（cyclin D1）、细胞周期蛋白依赖性激酶2（CDK2）、B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（BAX）蛋白的表达水平。结果：与PHN-0组相比，PHN-50、PHN-100、PHN-200组U251细胞增殖活力、克隆形成数、迁移和侵袭数、IL-8分泌水平、N-cadherin阳性率及其蛋白表达、TLR4、NF-κB、HMGB1、RAGE、cyclin D1、CDK2蛋白表达均显著降低（均P < 0.05），细胞凋亡率、E-cadherin阳性率及其蛋白表达、BAX/Bcl-2比值均显著升高（均P < 0.05）；同时过表达HMGB1则可逆转PHN对U251细胞增殖、迁移、侵袭及EMT的抑制作用和对凋亡的促进作用（均P < 0.05）。结论：PHN通过HMGB1/RAGE信号通路抑制胶质瘤U251细胞增殖、侵袭及EMT进程。

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

BACKGROUND:Digital three-dimensional reconstruction technology is gradually applied to orthopedic diseases with the advantages of visualization,accuracy and non-invasiveness,but there is less evidence-based support for its use in artificial hip hemiarthroplasty for intertrochanteric fractures of the femur in the elderly. OBJECTIVE:To investigate the application value and economic effects of digital three-dimensional reconstruction techniques in artificial hip hemiarthroplasty of intertrochanteric fractures of the femur in the elderly. METHODS:One hundred and thirty elderly patients with intertrochanteric femur fractures admitted to Zunyi First People's Hospital from January 2019 to December 2022 were selected and randomly divided into a control group(n=65)and an observation group(n=65).Artificial hip hemiarthroplasty was performed in both groups.The control group adopted the film template measurement method for manual preoperative planning while the observation group adopted a digital three-dimensional reconstruction technique.Preoperative planning and intraoperative actual application of prosthesis compliance rate,fibrinogen,D-dimer,bilateral femoral eccentric distance difference,bilateral lower limb length difference,Harris hip function score,visual analog scale score,excellent and good rate of hip function,complications,and hospitalization cost were observed in both groups. RESULTS AND CONCLUSION:(1)The proportion of acetabular side and femoral side prosthesis in grade 0(fully compliant)was higher in the observation group than that in the control group(P<0.05).(2)Fibrinogen and D-dimer levels in the observation group were lower than those in the control group 3 days after surgery(P<0.05).(3)The difference in bilateral femoral eccentric distance and the difference in bilateral lower limb length in the observation group were smaller than those in the control group immediately after surgery(P<0.05).The differences in Harris and visual analog scale scores were not significantly different between the two groups preoperatively,6 and 12 months postoperatively(P>0.05).There was no significant difference in excellent and good rate of hip function between the two groups 12 months postoperatively(P>0.05).(4)There was no significant difference in the complication rate between the two groups(P>0.05).The hospitalization cost of the observation group was higher than that of the control group(P<0.05).(5)It is indicated that digital three-dimensional reconstruction technology applied in artificial hip hemiarthroplasty of intertrochanteric femoral fracture in the elderly can not only accurately determine the prosthesis type before surgery,but also accurately reconstruct the bilateral lower limbs offline,but its hospitalization cost is high.

Trastuzumab has improved survival rates in human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC),but drug resistance leads to treatment failure.Natural killer(NK)cell-mediated antibody-dependent cell cytotoxicity(ADCC)represents an essential antitumor immune mechanism of trastuzumab.Traditional Chinese medicine(TCM)has been used for centuries to treat diseases because of its capacity to improve immune responses.Xianling Lianxia formula(XLLXF),based on the principle of"strengthening body and eliminating toxin",exhibits a synergistic effect in the trastuzumab treatment of patients with HER2-positive BC.Notably,this synergistic effect of XLLXF was executed by enhancing NK cells and ADCC,as demonstrated through in vitro co-culture of NK cells and BC cells and in vivo inter-vention experiments.Mechanistically,the augmented impact of XLLXF on NK cells is linked to a decrease in cytokine inducible Src homology 2(SH2)containing protein(CISH)expression,which in turn activates the Janus kinase 1(JAK1)/signal transducer and activator of transcription 5(STAT5)pathway.Collectively,these findings suggested that XLLXF holds promise for enhancing NK cell function and sensitizing pa-tients with HER2-positive BC to trastuzumab.

Objective By comparing with arthroscopic rotator cuff repair alone,to explore the efficacy and difference of leukocyte poor platelet-rich plasma(LP-PRP)and leukocyte rich platelet-rich plasma(LR-PRP)in arthroscopic rotator cuff repair.Methods Sixty patients with total rotator cuff tear accompanied by arthroscopic rotator cuff repair admitted to the Affiliated Hospital of North China University of Science and Technology from October 2021 to September 2022 were included and randomly divided into control group(n=20),LP-PRP group(n=20)and LR-PRP group(n=20).The control group only received arthroscopic rotator cuff repair.The LP-PRP group was injected with leukocyte poor platelet-rich plasma(LP-PRP)into the sutured torn tendon after the same operation,and the LR-PRP group was injected with leukocyte rich platelet-rich plasma(LR-PRP)into the sutured torn tendon after the same operation.The postoperative rehabilitation training plan of the three groups was the same,and the postoperative follow-up and evaluation were conducted for 1 year.It included pain score(VAS score),shoulder joint function score(CMS,UCLA,ASES score),retear rate and related complications.Results All patients were followed up.(1)VAS score:Compared with the LR-PRP group and the control group,the results were statistically significant only at 1,3 and 6 weeks after surgery(P<0.05);There was no statistical significance between the LR-PRP group and the control group at 1 week,3 weeks,6 weeks,3 months,6 months and 12 months after surgery(P>0.05).(2)CMS,UCLA and ASES scores:There were no significant differences between the LP-PRP group and the LR-PRP group at 3 months,6 months and 12 months after surgery(P>0.05);Compared with LP-PRP group and LR-PRP group,there were significant differences in each follow-up time point of control group(P<0.05).(3)Retear rate:In the LP-PRP group,there was 1 retear in the LR-PRP group(tear rate 5%),and 3 in the control group(tear rate 15%).There was no statistically significant difference between the three groups(P>0.05).(4)There were no postoperative complications in 60 patients.Conclusions Compared with arthroscopic rotator cuff repair alone,although the application of LP-PRP and LR-PRP could not reduce the rate of retear,it could significantly improve the shoulder joint function of patients,and LP-PRP could significantly reduce the pain of patients with rotator cuff injury in the early postoperative period(within 6 weeks),with no postoperative complications,and the short-term clinical results of patients were satisfactory.

Objective:To explore the disease spectrum and corresponding clinical indicators of infantile cholestasis so as to provide a basis for the diagnosis of this type of disease at an early stage.Methods:The clinical data was collected from 203 hospitalized children diagnosed with infantile cholestasis at the Department of Gastroenterology of Maternal and Child Health Care, Guiyang City, from January 2018 to March 2023, including 130 males and 73 females. Patients general condition, personal history, and blood biochemical test indicators, including liver and coagulation function, blood ammonia, blood lipid profile, blood sugar, TORCH, thyroid function, and others, were retrospectively analyzed after admission. Cholangiography and high-throughput gene sequencing were performed in certain patients. The etiology of the enrolled cases were analyzed. Children's clinical data were compared with distinct inherited metabolic liver diseases (Group A) and biliary atresia (Group B). The statistical analysis was conducted using the t-test, Mann-Whitney test, Kruskal-Wallis test, or χ2 test, according to different data. Results:In 33 cases, infectious factors—primarily CMV infection—were the etiology of cholestasis. Forty cases had aberrant bile duct development, primarily biliary atresia, choledochal cysts, and intrahepatic bile duct dysplasia. In 26 cases, genetic metabolic factors mainly included citrin protein deficiency, sodium-taurocholate co-transporting polypeptide deficiency, and Alagille syndrome. 11 cases had drug/poisoning factors (parenteral nutrition-associated cholestasis). 19 cases had idiopathic infantile cholestasis. Three cases had other factors; however, all of them had Kawasaki disease. 71 cases had an unclear diagnosis. There was no statistically significant difference in terms of gender and age between groups A and B ( P>0.05). The alkaline phosphatase (ALP) and bile acid levels were significantly higher in Group A than Group B, with a P<0.05, while the gamma glutamyltransferase (GGT), direct bilirubin (DBil), and albumin levels were lower than those in Group B, with a P<0.05. The cytomegalovirus infection rate was higher in Group B (62.50%) than Group A (34.62%), and the difference between the two groups was statistically significant ( χ2=3.89, P<0.05). The alanine aminotransferase, aspartate aminotransferase, GGT, DBil, and albumin were significantly lower in patients with citrin protein deficiency than those in patients with biliary atresia, while ALP, bile acid, and blood ammonia were higher than those in patients with biliary atresia. Patients with sodium-taurocholate co-transporting polypeptide deficiency had higher bile acid than patients with biliary atresia, while the DBil was lower than that in patients with biliary atresia, and the difference was statistically significant ( P<0.05). Conclusion:Infantile cholestasis etiology is diverse. ALP, bile acids, GGT, DBil, and albumin levels can serve as simple indicators for early-stage differentiation between inherited metabolic liver disease and biliary atresia. The cholestasis etiology should be determined as early as possible following biliary atresia exclusion by actively completing genetic metabolic gene detection.

Objective To explore the association between dietary quality and perceived stress among adult Chinese. Methods The China Health and Nutrition Survey (CHNS) was used to investigate the association between dietary quality and perceived stress in Chinese adults. The Chinese Perceived Stress Scale (CPSS) was used to assess the perceived stress in Chinese adults. Binary logistic regression models were utilized to explore the relationship between diet quality and perceived stress. Restricted cubic splines (RCS) were utilized to clarify the dose response relationship between diet quality and perceived stress. Results Binary logistic regression models revealed that adults with CHEI score ranged from P25 to P50 and higher than P75 had 15.1% (OR=0.849，95%CI：0.738-0.977) and 23.0% (OR=0.770，95%CI：0.666-0.891) reduced risk of high perceived stress after multivariable adjustment when compared with adults with CHEI score less than P25. RCS results showed that the OR value of high perceived stress risk decreased gradually with increasing CHEI score in the overall population, but this association was not statistically significant in adults with lower CHEI score. Conclusion High dietary quality is associated with a reduced risk of high perceived stress. This study provides a theoretical reference for the health effects of high dietary quality on high perceived stress risk reduction.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.