Chronic obstructive pulmonary disease (COPD), which predominantly affects middle-aged and elderly individuals, is associated with a significantly reduced quality of life and often triggers various other pulmonary conditions. Lung cancer, as one of the most prevalent and deadly pulmonary malignancies worldwide, poses a severe threat to global public health. The risk of developing lung cancer is markedly higher in COPD patients compared to the general population, indicating numerous associations between the two conditions that warrant in-depth investigation. Although a substantial body of research has explored the relationship between COPD and lung cancer, studies focusing on the molecular mechanisms underlying their connection remain limited. This article reviews the latest research progress on the mechanisms of COPD complicated by lung cancer from four perspectives: the role of chronic pulmonary inflammation, programmed cell death, genetic and molecular interactions, and dysbiosis of the pulmonary microbiome. The aim of this article is to provide new insights and references for the prevention and therapeutic strategies of COPD complicated with lung cancer.

Objective:To analyze the optical coherence tomography (OCT) imaging characteristics in patients with Coats disease and their value in predicting macular fibrosis.Methods:A nested case-control study was performed.A total of 43 patients (43 eyes) diagnosed with Coats disease through color fundus photography, ocular B-scan ultrasonography, fundus fluorescein angiography, and spectral-domain OCT examination were enrolled from January 2008 to October 2021 at the Xijing Hospital.Among them, there were 40 males and 3 females, aged from 2 to 60 years old, with a median age of 13 years.Macular fibrosis was used as an indicator of poor prognosis, and patients were divided into two groups based on whether macular fibrosis occurred at the end of follow-up.The differences in OCT characteristics between two groups were compared and logistic regression analysis was used to identify the risk factors for macular fibrosis.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Xijing Hospital of Fourth Military Medical University (No.KY20202009-C-1).Results:The OCT clinical features of 43 cases of Coats disease included intraretinal hard exudates in 43 eyes (100%), subretinal fluid in 21 eyes (48.8%), macular cysts in 17 eyes (27.9%), subretinal exudates in 9 eyes (20.9%), anterior retinal hyperreflective dots in 7 eyes (16.3%), epiretinal membrane in 21 eyes (48.8%), and intraretinal fluid in 22 eyes (51.2%).In color fundus photos of 41 eyes, 38 eyes (93.0%) had hard exudates distributed in the posterior pole and 27 eyes (65.9%) had the mid-peripheral region.OCT examination showed that hard exudates were distributed in the inner nuclear layer in 35 eyes (81.4%) and the outer nuclear layer in 33 eyes (76.7%).Among 21 eyes with exudative retinal detachment detected by OCT, 9 eyes (42.9%) were detected by fundus photography and 18 eyes (85.7%) were detected by B-scan ultrasonography.The proportions of eyes with subretinal fluid and subretinal exudates were higher in the macular fibrosis group than in the non-macular fibrosis group, and the differences were statistically significant ( χ2=20.755, P<0.001; χ2=6.133, P=0.013).Logistic regression analysis showed that the presence of subretinal fluid was a risk factor for macular fibrosis (odds ratio=48.345, 95% confidence interval: 4.272-547.066, P=0.002). Conclusions:OCT examination can detect subretinal fluid, subretinal exudates, macular cysts, macular exudates, and hyperreflective spots in the retina of patients with Coats disease.Subretinal fluid is a risk factor for macular fibrosis.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective     To investigate the accuracy of 18F-FDG positron emission tomography/computed tomography (PET/CT) combined with CT three-dimensional reconstruction (CT-3D) in the differential diagnosis of benign and malignant pulmonary nodules. Methods     The clinical data of patients who underwent pulmonary nodule surgery in the Department of Thoracic Surgery, Northern Jiangsu People's Hospital from July 2020 to August 2021 were retrospectively analyzed. The preoperative 18F-FDG PET/CT and chest enhanced CT-3D and other imaging data were extracted. The parameters with diagnostic significance were screened by the area under the receiver operating characteristic (ROC) curve (AUC). Three prediction models, including PET/CT prediction model (MOD PET), CT-3D prediction model (MOD CT-3D), and PET/CT combined CT-3D prediction model (MOD combination), were established through binary logistic regression, and the diagnostic performance of the models were validated by ROC curve. Results     A total of 125 patients were enrolled, including 57 males and 68 females, with an average age of 61.16±8.57 years. There were 46 patients with benign nodules, and 79 patients with malignant nodules. A total of 2 PET/CT parameters and 5 CT-3D parameters were extracted. Two PET/CT parameters, SUVmax≥1.5 (AUC=0.688) and abnormal uptake of hilar/mediastinal lymph node metabolism (AUC=0.671), were included in the regression model. Among the CT-3D parameters, CT value histogram peaks (AUC=0.694) and CT-3D morphology (AUC=0.652) were included in the regression model. Finally, the AUC of the MOD PET was verified to be 0.738 [95%CI (0.651, 0.824)], the sensitivity was 74.7%, and the specificity was 60.9%; the AUC of the MOD CT-3D was 0.762 [95%CI (0.677, 0.848)], the sensitivity was 51.9%, and the specificity was 87.0%; the AUC of the MOD combination was 0.857 [95%CI (0.789, 0.925)], the sensitivity was 77.2%, the specificity was 82.6%, and the differences were statistically significant (P<0.001). Conclusion     18F-FDG PET/CT combined with CT-3D can improve the diagnostic performance of pulmonary nodules, and its specificity and sensitivity are better than those of single imaging diagnosis method. The combined prediction model is of great significance for the selection of surgical timing and surgical methods for pulmonary nodules, and provides a theoretical basis for the application of artificial intelligence in the pulmonary nodule diagnosis.

By applying "homeostasis" to the study of the meridian and collateral system， the concept of meridian and collateral homeostasis has been proposed which refers to a balanced and stable state of meridian and collateral system， and plays an important role in maintaining body health and can provide a reference for the diagnosis and treatment of diseases. Phenomics realizes the cross-scale correlation from micro-phenotypic data， such as genome， proteome， and metabolome， to macro-phenotypic data， such as physiological state， behavioral activities， and external manifestations. From the perspective of phenomics， this paper proposes a meridian and collateral homeostasis dynamic mapping model of "macroscopic signs and microscopic expression". This model combines macro signs such as the four examinations of traditional Chinese medicine （TCM）， biophysical indicators of acupoints， and micro expression information such as genes， proteins， and metabolism， and systematically investigates the relationship between meridian and collateral homeostasis and health and disease， thereby providing ideas and references for the identification of pre-disease states as well as precise diagnosis and treatment in TCM.

OBJECTIVE To explore the lipid-regulating mechanism of the classic prescription Zexie Decoction on hyperlipidemia model mice.METHODS ELISA method was used to detect the four blood lipid indexes,liver function indicators and cholesterol acyltransferase levels in serum.HE and Oil Red O staining were used to determine the pathology of liver tissue.Network pharmacology was used to predict the lipid-lowering related targets of Zexie Decoction,and the GO function and KEGG pathway enrichment analyses of the intersection targets were realized.PCR chip technology was used to detect the target genes for network pharmacology screening,and qPCR and Western blot were used to detect gene and protein expression levels.RESULTS Zexie Decoction significantly regula-ted the four blood lipid indexes in hyperlipidemia model mice,improved the increase in liver damage indicators caused by high lipids,and had a reverse regulatory effect on the key enzymes HMGR and CYP7A1 of lipid metabolism and the lipid transporters ABCA1 and Apo-A1 in liver tissue.HE and Oil Red O staining showed that Zexie Decoction improved the pathological morphology of liver tissue,reduced lipid deposition in liver tissue,and significantly decreased the positive area ratio(P<0.01).The PCR chip obtained 44 re-verse-regulated genes,GO functional enrichment analysis obtained 266 entries,and KEGG pathway enrichment analysis screened 99 signaling pathways.The results of qPCR and Western blot showed that Zexie Decoction significantly downregulated the expression of PIK3CG,AKT1,and IL-6 genes(P<0.05,P<0.01),upregulated the expression of ABCG1 gene(P<0.05),downregulated PI3Kinase p110β,p-AKT(Ser473)and SREBP-1c protein expression levels(P<0.01),and reversely regulated miR21-5p(P<0.01).CONCLUSION Zexie Decoction has a significant regulatory effect on lipid metabolism in hyperlipidemia model mice and can improve liver damage caused by hyperlipidemia.Its lipid-regulating effect may be related to regulating cholesterol metabolism and transport in the body,and is closely linked to the miR21/PI3K-Akt/SREBP pathway.The lipid-regulating effect of the whole formula of Zexie Decoction is better than that of a single herb.

ObjectiveA method was developed for the rapid determination of 18 common disinfection by-products including halogenated oxides and haloacetic acid （HAAs） in drinking water by high performance liquid chromatography tandem mass spectrometry （HPLC-MS/MS）. MethodThe water sample was filtered by 0.22 μm hydrophilic membrane then the analytes were separated on a PFP （2.1 mm× 100 mm， 2.7 μm） pentafluorophenyl column with 0.1% acetic acid and acetonitrile as mobile phase gradient elution. Ionization in anionic electrospray mode was detected by multi-reaction monitoring （MRM） mode. The external standard method was used for quantitation. ResultsThe correlation coefficients of 18 disinfection by-products were above 0.999 in the corresponding linear range. The average spiked recoveries of 1， 10 and20 times of LOQ of each analyte were 91.6%‒101.8%， and the relative standard deviation （RSD） was 1.2%‒6.4%. The LOD and LOQ were 0.020‒2 μg·L^-1 and 0.050‒5 μg·L^-1， respectively. ConclusionThis method is simple， sensitive and accurate， and could be used for the routine analysis of 18 common disinfection by-products in drinking water.

Objective:To investigate the molecular expression and pathological features of endothelial cell (EC) in a murine model of choroidal neovascularization (CNV) based on single-cell RNA sequencing (scRNA-seq).Methods:Six C57BL/6 mice aged 6-8 weeks were randomly divided into two groups, with 3 mice in each group.Bilateral eyeballs were enucleated.The choroidal tissues from the two groups were isolated by shearing the complex and scraping the choroid, respectively.Single-cell suspension was prepared by continuous digestion with trypsin/type Ⅰ collagenase at 37 ℃, and the cell viability and EC ratio were detected by flow cytometry to determine the preparation method of single-cell suspension.Another 6 mice were randomly assigned into the control group and the CNV group, with 3 mice in each group.The CNV model was induced by laser photocoagulation and single-cell suspensions were prepared 7 days after modeling.Gene expression library construction was performed using the Chromi-um (10x Genomics) instrument.High throughput sequencing was performed using the Illumina Novaseq6000 to obtain the expression matrix.The EC subpopulations were classified according to previous researches and the Cellmarker database.Pseudo-time analysis was performed in EC, revealing the gene expression matrix of different states.CNV-EC were further selected with preliminary analysis of the expression characteristics.Another 6 mice were selected to establish the CNV model and eyeball frozen sections were prepared 7 days after modeling.Expression and distribution as well as the area percentage of EC marker Pecam1, mitochondrial outer membrane proteins Tomm20 and mt-Co1, and capillary markers Kdr and Plvap were observed by immunofluorescence staining, and the vascular diameter was calculated.The use and care of animals followed the ARVO statement.This study protocol was approved by the Experimental Animal Welfare and Ethics Committee of Air Force Military Medical University (No.20200181).Results:The cell viability of the single-cell suspension prepared from choroidal-scleral fragments and choroidal scrapings was 99.4% and 99.1%, respectively, both of which met the sequencing requirements.The percentage of EC detected by flow cytometry was approximately 1.58%.The scRNA-seq result revealed that both the normal control and CNV groups contained 13 choroidal cell clusters.Compared with the normal control group, the proportions of rod/cone photoreceptor cells, EC and hematopoietic cells all increased, while the retinal pigment epithelium (RPE) and Schwan cells reduced in the CNV group.Among all clusters, EC constituted 18.4%.The pseudo-time analysis demonstrated that EC could be further divided into 4 states.The percentage of state 2 EC was 29.1% in the CNV group, which was significantly higher than 9.5% in the normal control group.Differentially expressed gene analysis showed that the expression of mitochondrion-related genes, including mt-Nd4 and mt-Atp6, were upregulated in state 2 EC, while capillary-related genes, including Kdr and Esm1, were downregulated.Immunofluorescent staining revealed that the area of Tomm20 and mt-Co1 in Pecam1-positive EC in the CNV area was (19.50±4.68)% and (4.64±2.82)%, respectively, which were both higher than (3.00±2.09)% and (0.18±0.34)% in normal area ( t=7.88, 3.84; both at P<0.01). The area of Kdr and Plvap in Pecam1-positive EC in the CNV area was (1.50±0.29)% and (0.79±0.97)%, respectively, which were both lower than (31.30±5.44)% and (10.43±2.28)% in the normal area ( t=13.40, 9.48; both at P<0.01). The vascular diameter in the CNV area was (5.52±1.85)μm, which was larger than (4.21±1.84)μm in the normal area ( t=9.57, P<0.001). Conclusions:When CNV occurs, the proportion of EC in choroid increases, and CNV-EC shows pathologic features of mitochondrial metabolic activation and loss of capillary properties, suggesting the mitochondrial activation of EC may play a role in the formation of CNV.

Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells