Objective To identify the key biomarkers for diagnosing chronic obstructive pulmonary disease(COPD)complicated with pulmonary arterial hypertension(PAH)using bioinformatics,and validate their clinical significance.Methods High-throughput sequencing data analysis was employed to identify differentially expressed genes(DEGs)in COPD-PAH.Functional enrichment analysis was then conducted to explore the biological functions of these DEGs.Machine learning methods,including least absolute shrinkage and selection operator(LASSO),random forest(RF),and support vector machine-recursive feature elimination(SVM-RFE),were utilized to screen 5 potential biomarkers.Single-cell analysis was performed to reveal the expression patterns of these key genes in macrophages.The clinical significance of these biomarkers was further validated using peripheral blood mononuclear cells(PBMC)data.A mouse model of COPD-PAH was established using hypoxia exposure.Sixteen mice(either sexes,8 weeks old,weighing 20～22 g)were randomly divided into a hypoxia group[O2(10.0±0.5)%,COPD-PAH,n=8]and a normoxia group(COPD,n=8).Immunofluorescence assay was used to label the key biomarkers,and their expression levels were quantified.Results A total of 28 DEGs(|Log2FC|≥2,P<0.05)were identified in COPD-PAH patients.Functional enrichment analysis indicated that DEGs in COPD were primarily associated with major histocompatibility complex(MHC)Ⅱ and cell division,and involved in lysosomes,oxidative phosphorylation,and cell cycle pathways(P<0.05).Machine learning identified 5 potential biomarkers(GRN,KLF4,SHTN1,LRP1,and GPNMB),and subsequent single-cell analysis revealed that these markers exhibited reverse expression patterns during disease progression.A nomogram model constructed based on PBMC data yielded an area under the curve(AUC)of 0.907 in diagnosing COPD-PAH.GRN,KLF4,SHTN1,LRP1 and GPNMB were significantly upregulated in the COPD-PAH group(P<0.05).Conclusion GRN,KLF4,SHTN1,LRP1 and GPNMB are identified as key biomarkers for the prediction and diagnosis of COPD-PAH,which providing new insights for the clinical and treatment of the condition.

Objective:To analyze the electroencephalogram(EEG) average relative power spectrum in patients with unipolar and bipolar depression under the eyes-open and eyes-closed resting states.Methods:A total of 38 patients with unipolar depression (UD group), 48 patients with bipolar depression (BD group), and 43 healthy controls (HC group) were recruited from August 2022 to December 2023.The 64-channel EEG was recorded under eyes-open (EO) and eyes-closed (EC) resting states which alternated twice. The Mann-Whitney U test and Kruskal-Wallis H test were performed by SPSS 25.0 software. Results:There were no significant differences in the average relative power of delta and beta bands among the UD, BD and HC groups in all EO and EC states (all P>0.05). The average relative power of theta band in the three groups showed statistically significant differences in all EO and EC states ( H=7.852-12.583, all P<0.05). Further pairwise comparisons showed that in the first EO and EC stage, the average relative power of theta band of the UD and BD groups were significantly higher than that of the HC group (EO1: 0.18(0.17, 0.21), 0.19(0.16, 0.21), 0.16(0.14, 0.18), EC1: 0.15(0.13, 0.21), 0.15(0.13, 0.20), 0.13(0.10, 0.16); all P<0.05).In the second EO and EC stage, the average relative power of theta band of the BD group was significantly higher than that of the HC group (EO2: 0.18(0.15, 0.22), 0.16(0.14, 0.18), EC2: 0.15(0.13, 0.19), 0.13(0.11, 0.16); both P<0.05).There were statistically significant differences in the average relative power of alpha band among the three groups in the first EO and EC stage, as well as the second EC stage ( H=5.027-10.668, all P<0.05). Further pairwise comparisons showed that in the first EO stage, the average relative power of alpha band in the BD group was significantly higher than that in the UD group (0.20(0.16, 0.25), 0.14(0.11, 0.22), P=0.003), and in the following EC stages, the average relative power of alpha band in the UD group was significantly lower than that in the HC group (EC1: 0.40(0.33, 0.46), 0.51(0.40, 0.58), EC2: 0.41(0.35, 0.50), 0.48(0.43, 0.58); both P<0.05). Conclusion:At the initial stage of the resting state, both unipolar and bipolar depression patients demonstrate abnormal theta band activity under the eyes-open and eyes-closed states, while the alpha band activity under the eyes-open condition differs between the two groups of patients. These findings may provide potentially objective biomarkers to assist the diagnosis of unipolar and bipolar depression patients in clinical settings.

Objective:To analyze the electroencephalogram(EEG) average relative power spectrum in patients with unipolar and bipolar depression under the eyes-open and eyes-closed resting states.Methods:A total of 38 patients with unipolar depression (UD group), 48 patients with bipolar depression (BD group), and 43 healthy controls (HC group) were recruited from August 2022 to December 2023.The 64-channel EEG was recorded under eyes-open (EO) and eyes-closed (EC) resting states which alternated twice. The Mann-Whitney U test and Kruskal-Wallis H test were performed by SPSS 25.0 software. Results:There were no significant differences in the average relative power of delta and beta bands among the UD, BD and HC groups in all EO and EC states (all P>0.05). The average relative power of theta band in the three groups showed statistically significant differences in all EO and EC states ( H=7.852-12.583, all P<0.05). Further pairwise comparisons showed that in the first EO and EC stage, the average relative power of theta band of the UD and BD groups were significantly higher than that of the HC group (EO1: 0.18(0.17, 0.21), 0.19(0.16, 0.21), 0.16(0.14, 0.18), EC1: 0.15(0.13, 0.21), 0.15(0.13, 0.20), 0.13(0.10, 0.16); all P<0.05).In the second EO and EC stage, the average relative power of theta band of the BD group was significantly higher than that of the HC group (EO2: 0.18(0.15, 0.22), 0.16(0.14, 0.18), EC2: 0.15(0.13, 0.19), 0.13(0.11, 0.16); both P<0.05).There were statistically significant differences in the average relative power of alpha band among the three groups in the first EO and EC stage, as well as the second EC stage ( H=5.027-10.668, all P<0.05). Further pairwise comparisons showed that in the first EO stage, the average relative power of alpha band in the BD group was significantly higher than that in the UD group (0.20(0.16, 0.25), 0.14(0.11, 0.22), P=0.003), and in the following EC stages, the average relative power of alpha band in the UD group was significantly lower than that in the HC group (EC1: 0.40(0.33, 0.46), 0.51(0.40, 0.58), EC2: 0.41(0.35, 0.50), 0.48(0.43, 0.58); both P<0.05). Conclusion:At the initial stage of the resting state, both unipolar and bipolar depression patients demonstrate abnormal theta band activity under the eyes-open and eyes-closed states, while the alpha band activity under the eyes-open condition differs between the two groups of patients. These findings may provide potentially objective biomarkers to assist the diagnosis of unipolar and bipolar depression patients in clinical settings.

Objective To scan and accurately reconstruct mandible models printed via fused deposition modeling(FDM)that contain screw path information,using cone-beam CT(CBCT),to achieve the digital transfer of preoperative model screw paths.Methods CBCT scans were conducted on 12 FDM-printed mandibular models(Model1 group)intended for prebending reconstruction plates.Mim-ics software was employed to reconstruct scanned data into mandibular models(Model2 group)and extract digital screw path informa-tion.Model2 was then compared with original models(Model0 group)in three dimensions,evaluating reconstruction accuracy through root mean square(RMS).Reconstruction parameters were optimized to enable automatic matching of Model2 with Model0,facilitating precise digital transfer of screw paths.In clinical application,this method was utilized to produce digital short-segment drilling guides,assisting in the reduction surgery of three mandibular fracture patients.Results Model2 demonstrated automatic matching with Model0,exhibiting detailed surface characteristics and clear screw path position and orientation information.The RMS was measured at(0.32±0.09)mm.Utilization of digital segmented screw path transfer guides assisted in the satisfactory reduction surgery of three pa-tients with comminuted mandibular fractures.Conclusion CBCT scanning of FDM-printed preoperative models accurately captures screw path position and orientation information,enabling digital transfer of screw paths and providing a novel method for precise design of digital surgical guides.

Objective To scan and accurately reconstruct mandible models printed via fused deposition modeling(FDM)that contain screw path information,using cone-beam CT(CBCT),to achieve the digital transfer of preoperative model screw paths.Methods CBCT scans were conducted on 12 FDM-printed mandibular models(Model1 group)intended for prebending reconstruction plates.Mim-ics software was employed to reconstruct scanned data into mandibular models(Model2 group)and extract digital screw path informa-tion.Model2 was then compared with original models(Model0 group)in three dimensions,evaluating reconstruction accuracy through root mean square(RMS).Reconstruction parameters were optimized to enable automatic matching of Model2 with Model0,facilitating precise digital transfer of screw paths.In clinical application,this method was utilized to produce digital short-segment drilling guides,assisting in the reduction surgery of three mandibular fracture patients.Results Model2 demonstrated automatic matching with Model0,exhibiting detailed surface characteristics and clear screw path position and orientation information.The RMS was measured at(0.32±0.09)mm.Utilization of digital segmented screw path transfer guides assisted in the satisfactory reduction surgery of three pa-tients with comminuted mandibular fractures.Conclusion CBCT scanning of FDM-printed preoperative models accurately captures screw path position and orientation information,enabling digital transfer of screw paths and providing a novel method for precise design of digital surgical guides.

Objective To investigate the hemodynamic effects of enhanced external counterpulsation(EECP)on cerebral arteries with different stenoses.Methods Zero-dimensional/three-dimensional multiscale hemodynamic models of cerebral arteries with different stenoses were constructed.Numerical simulations of the EECP hemodynamics were performed under different counterpulsation modes to quantify several hemodynamic indicators of the cerebral arteries.Among them,the mean time-averaged wall shear stress(TAWSS)downstream of the stenosis was in the range of 4-7 Pa,a low percentage of TAWSS risk area,and high narrow branch flow were considered to inhibit the development of atherosclerosis and create a good hemodynamic environment.Results For cerebral arteries with 50%,60%,70%,and 80%stenosis,the hemodynamic environment was optimal in counterpulsation mode when the moment of cuff deflation was 0.5,0.6,0.7,and 0.7 s within the cardiac cycle.Conclusions For 50%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.5 s should be selected.For 60%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.6 s should be selected.For 70%or 80%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.7 s should be selected.As stenosis of the cerebral arteries increases,the pressure duration should be prolonged.This study provides a theoretical reference for the EECP treatment strategy for patients with ischemic stroke with different stenoses.

Objective To compare the clinical efficacy of ankle arthroscopy combined with closed reduction guide and conventional surgical incision in the treatment of trimalleolar fracture.Methods A total of 60 patients with ankle fracture were divided into two groups according to different surgical plans:the ankle arthroscopy combined with closed reduction guide surgery group(arthroscopy group)and the conventional incision surgery group(incision group),with 30 cases in each group.The operative time,intraoperative blood loss and complications of the two groups were observed and compared.Pain and functional recovery of patients were evaluated by the American Orthopaedic Foot&Ankle Society(AOFAS)ankle and hind foot scores and Foot and Ankle Disability Index(FADI)scores.Results All 60 patients were followed up.Compared with the arthroscopy group,patients in the incision group had a longer surgical time,a shorter incision length in the medial malleolus,a reduced number of cases of skin numbness and reduced bleeding(P＜0.05).The AOFAS score and the FADI score at 12 months after surgery were higher in the arthroscopic group than those of the incision group(P＜0.05).After 12 months of surgery,the AOFAS score in patients without cartilage injury of the arthroscopic group were higher than those of patients with cartilage injury(P＜0.05),while there were no significant differences in pain and force line scores between patients with cartilage injury and patients without cartilage injury(P＞0.05).Conclusion The application of ankle arthroscopy combined with closed reduction guide in the treatment of trimalleolar fracture can achieve better postoperative results,but it has no obvious advantages in operation time and incision infection compared with the incision surgery.

Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

Cell cycle plays a crucial role in cell development. Cell cycle progression is mainly regulated by cyclin dependent kinase (CDK), cyclin and endogenous CDK inhibitor (CKI). Among these, CDK is the main cell cycle regulator, binding to cyclin to form the cyclin-CDK complex, which phosphorylates hundreds of substrates and regulates interphase and mitotic progression. Abnormal activity of various cell cycle proteins can cause uncontrolled proliferation of cancer cells, which leads to cancer development. Therefore, understanding the changes in CDK activity, cyclin-CDK assembly and the role of CDK inhibitors will help to understand the underlying regulatory processes in cell cycle progression, as well as provide a basis for the treatment of cancer and disease and the development of CDK inhibitor-based therapeutic agents. This review focuses on the key events of CDK activation or inactivation, and summarizes the regulatory processes of cyclin-CDK at specific times and locations, as well as the progress of research on relevant CDK inhibitor therapeutics in cancer and disease. The review concludes with a brief description of the current challenges of the cell cycle process, with the aim to provide scientific references and new ideas for further research on cell cycle process.
Cyclin-Dependent Kinases/metabolism* ; Cyclins/metabolism* ; Protein Serine-Threonine Kinases ; Cell Cycle Proteins/metabolism* ; Cell Cycle/physiology* ; Cyclin-Dependent Kinase 2