Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

ObjectiveThis study proposes a novel single-cell protein localization method based on a class perception graph convolutional network (CP-GCN) to overcome several critical challenges in protein microscopic image analysis, including the scarcity of cell-level annotations, inadequate feature extraction, and the difficulty in achieving precise protein localization within individual cells. The methodology involves multiple innovative components designed to enhance both feature extraction and localization accuracy. MethodsFirst, a class perception module (CPM) is developed to effectively capture and distinguish semantic features across different subcellular categories, enabling more discriminative feature representation. Building upon this, the CP-GCN network is designed to explore global features of subcellular proteins in multicellular environments. This network incorporates a category feature-aware module to extract protein semantic features aligned with label dimensions and establishes a subcellular relationship mining module to model correlations between different subcellular structures. By doing so, it generates co-occurrence embedding features that encode spatial and contextual relationships among subcellular locations, thereby improving feature representation. To further refine localization, a multi-scale feature analysis approach is employed using the K-means clustering algorithm, which classifies multi-scale features within each subcellular category and generates multi-cell class activation maps (CAMs). These CAMs highlight discriminative regions associated with specific subcellular locations, facilitating more accurate protein localization. Additionally, a pseudo-label generation strategy is introduced to address the lack of annotated single-cell data. This strategy segments multicellular images into single-cell images and assigns reliable pseudo-labels based on the CAM-predicted regions, ensuring high-quality training data for single-cell analysis. Under a transfer learning framework, the model is trained to achieve precise single-cell-level protein localization, leveraging both the extracted features and pseudo-labels for robust performance. ResultsExperimental validation on multiple single-cell test datasets demonstrates that the proposed method significantly outperforms existing approaches in terms of robustness and localization accuracy. Specifically, on the Kaggle 2021 dataset, the method achieves superior mean average precision (mAP) metrics across 18 subcellular categories, highlighting its effectiveness in diverse protein localization tasks. Visualization of the generated CAM results further confirms the model’s capability to accurately localize subcellular proteins within individual cells, even in complex multicellular environments. ConclusionThe integration of the CP-GCN network with a pseudo-labeling strategy enables the proposed method to effectively capture heterogeneous cellular features in protein images and achieve precise single-cell protein localization. This advancement not only addresses key limitations in current protein image analysis but also provides a scalable and accurate solution for subcellular protein studies, with potential applications in biomedical research and diagnostic imaging. The success of this method underscores the importance of combining advanced deep learning architectures with innovative training strategies to overcome data scarcity and improve localization performance in biological image analysis. Future work could explore the extension of this framework to other types of microscopic imaging and its application in large-scale protein interaction studies.

ObjectiveTo investigate the prevalence rate of chronic non-communicable diseases （NCDs） and the association with quality of life in middle-aged and elderly patients with HIV/AIDS. MethodsThis cross-sectional study surveyed 432 patients with HIV/AIDS （aged≥45 years） in the Infectious Disease Center in Guangzhou Eighth People’s Hospital of Guangzhou Medical University， and 366 participants were included in the analysis after quality control. A questionnaire and the EuroQol 5-Dimensional 3-level version （EQ-5D-3L） were used to investigate NCDs and quality of life and Tobit regression model was used to estimate the association between chronic diseases and quality of life. ResultsAmong the 366 participants， 29（7.9%） had cardiovascular disease， 45（12.3%） had hypertension， 122（33.3%） had hyperglycemia， 151（41.3%）had hyperlipidemia，7（1.9%） had cancer， 17 （4.6%） had chronic kidney disease， 38 （10.4%） had chronic liver disease， 21（5.7%） had musculoskeletal disorders， and 253（69.1%） suffered from at least one type of chronic diseases. The median （lower and upper quartiles） of EQ-5D utility index was 1.000（0.964~1.000）. Multivariate Tobit regression results of the total population showed that cancer ［b_a=-0.08，95%CI （-0.15，-0.01），P=0.036］， chronic kidney disease ［b_a=-0.07， 95%CI （-0.12，-0.02），P=0.006］， musculoskeletal disease ［b_a=-0.09， 95%CI （-0.13， -0.05），P<0.001］， and ≥3 types of chronic diseases［b_a=-0.05， 95%CI（-0.08，-0.01），P=0.013］ were negatively correlated with EQ-5D utility index. The stratified analysis results of different CD4+T cell levels showed that hypertension ［b_a=-0.07， 95%CI （-0.12， -0.02）， P=0.007］， chronic kidney disease ［b_a=-0.10，95%CI （-0.18，-0.03）， P=0.006］， musculoskeletal disease ［b_a=-0.15， 95%CI （-0.22，-0.07）， P<0.001］ and ≥3 types of chronic diseases ［b_a=-0.09， 95%CI （-0.09， -0.01）， P<0.001］ were negatively correlated with EQ-5D utility index in the group with CD4≤500 （cells/μL）， whereas cancer［b_a=-0.11， 95%CI （-0.20，-0.01）， P=0.031］ was negatively correlated with EQ-5D utility index in the group with CD4＞500（cells/μL）. ConclusionsThe prevalence rate of chronic non-communicable diseases in middle-aged and elderly patients with HIV/AIDS is relatively high. The classification of NCDs such as cancer or chronic kidney disease or other chronic diseases and the numbers of NCDs categories are negatively correlated with quality of life. However，this association varies among patients with HIV/AIDS of different CD4+T cell levels. It is suggested that we should try to prevent and identify NCDs at an early stage， strengthen linkages and integration of health services for AIDS and chronic NCDs， and jointly manage and control AIDS with chronic diseases to improve the quality of life among people living with HIV/AIDS.

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G^-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G^- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Objective To evaluate the clinical efficacy of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus traditional Chinese medicine(TCM)bone-setting manipulations for the treatment of moderate hallux valgus.Methods A retrospective study was conducted.A total of 49 patients(62 feet)with moderate hallux valgus were treated with Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate,and were given TCM bone-setting manipulations before the operation,during the operation,and after the operation.The efficacy was evaluated by using the Visual Analogue Scale(VAS)score and the American Orthopedic Foot and Ankle Society(AOFAS)forefoot score after the operation.Before the operation and 12 months after the operation,the hallux valgus angle(HVA),intermetatarsal angle(IMA)between the first and second metatarsal bone,and the distal metatarsal articular angle(DMAA)showed by X-ray imaging in the weight-bearing position of the foot were recorded.Results(1)All of the 49 patients were followed up for 12 to 24 months,with a mean of(20.6±3.1)months.(2)The X-ray imaging assessment showed that 12 months after the operation,the mean HVA,IMA and DMAA values of the 49 patients(62 feet)were significantly lower than those before the operation,and the differences were all statistically significant(P＜0.01).(3)Twelve months after the operation,the pain VAS score of 49 patients was(3.14±1.21)points,which was significantly lower than the preoperative score points(7.26±2.52),and the difference was statistically significant(P＜0.01).(4)The assessment of joint function showed that 12 months after the operation,the scores of various AOFAS items of pain,function and hallux alignment as well as the overall AOFAS scores of 49 patients were significantly higher than those before the operation,and the differences were statistically significant(P＜0.01).(5)For the 62 feet in 49 patients,the excellent efficacy was achieved in 53 feet,good efficacy was achieved in 7 feet,and fair efficacy was achieved in 2 feet,with the fine rate of 96.77%(60/62).Conclusion For the treatment of moderate hallux valgus,the application of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus TCM bone-setting manipulations is effective on promoting the reset of hallux-metatarsophalangeal joint,restoring the balance of the joint,and maintaining the equilibrium state of the joint through postoperative rehabilitation guidance.The combined therapy exerts certain efficacy,reduces the recurrence rate,and eventually achieves the early rehabilitation after the operation.

Objective To investigate the value of computer-assisted quantification of pulmonary embolism volume(PEV)in identifying mild-to-high-risk acute pulmonary embolism(APE).Methods We retrospectively enrolled 143 patients with suspected APE confirmed by computed tomography pulmonary angiography(CTPA)at Yan'an University Affiliated Hospital from January 2017 to December 2020.According to the 2018 Chinese Guidelines for Diagnosis,Treatment and Prevention of Pulmonary Thromboembolism,all the patients were divided into low-risk group(n=88)and mild-to-high-risk group(n=55).We collected the patients'basic demographic data,clinical manifestations,and serum levels of N-terminal-B type natriuretic peptide precursor(NT-proBNP)and D-dimer.Based on CTPA images,the degree of pulmonary thromboembolism was artificially evaluated to obtain the pulmonary artery occlusion index(PAOI).The thrombus was segmented using the pulmonary embolism detection tool based on digital lung,and PEV was calculated.We compared the differences in clinical and laboratory indicators and PAOI and PEV between the two risk groups.We analyzed the value of PAOI and PEV in identifying mild-to-high-risk APE using receiver operating characteristic(ROC)curves,and used Logistic regression analysis to identify independent risk factors in predicting mild-to-high-risk APE.Different models were established.Results Compared with the low-risk group,APE patients in the mild-to-high-risk group were older(P＜0.05),had lower diastolic blood pressure(P＜0.05),higher levels of D-dimer and NT-proBNP(P＜0.05),lower levels of platelet count,arterial oxygen partial pressure and arterial carbon dioxide partial pressure(P＜0.05),and higher levels of PAOI and PEV(P＜0.001).ROC curve analysis showed that the area under the curve for PEV in identifying mild-to-high-risk APE was 0.809(95％CI:0.734-0.884),while that for PAOI was 0.753(95％CI:0.667-0.839).Logistic regression analysis showed that PEV and NT-proBNP were independent risk factors for mild-to-high-risk APE(P＜0.05).Conclusion PEV and NT-proBNP are independent risk factors for mild-to-high-risk APE.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

Objective:The human peripheral blood lymphocyte cell line 8E5 is capable of secreting non-infectious HIV-1 viral particles. By targeting the POL region of the HIV-1 proviral gene integrated into the genome of 8E5 cell line and constructing a monoclonal cell line containing a drug resistance mutation site in the POL region using CRISPR/Cas9 point mutation technology, safe and stable HIV-1 genotypic drug resistance test quality control materials can be prepared.Methods:8E5 cells were co-transfected with sgRNA (single guide RNA) and Cas9 coexpression vector and Donor ssODN (donor single-stranded oligonucleotides) carrying the target mutation sites. The positive monoclonal cell lines were obtained through flow microtiter plate sorting, and the editing efficacy of the targeted mutations was validated by Sanger sequencing. Sanger sequencing was performed to verify the editing effect of the targeted mutations on the HIV virus particles secreted into the supernatant of the monoclonal cell lines cultured to the 3rd, 5th and 7th generations.Results:A double sgRNA and Cas9 coexpression vector was successfully constructed and co-transfected with a Donor ssODN carrying the drug-resistant mutation site Q151M to the 8E5 cell line, resulting in the desired outcome. The sequencing result of the target site confirmed the successful mutation at the resistance site and the establishment of a monoclonal homozygous cell line. The Q151M mutation site was detected in non-infectious HIV-1 virus particles secreted by the 8E5 Q151M cell line after transmission. Conclusions:The cell line 8E5 Q151M was successfully constructed using CRISPR/Cas9 point mutation technology to stably carry the Q151M drug resistance mutation site, which provides a new technological platform for the preparation of quality-control materials for testing HIV-1 genotypic drug resistance.

Cathepsins,the most abundant hydrolases in lysosomes,are responsible for the degradation of various substrates.Increasing evidence suggests that cathepsins play important roles in neurodegenerative diseases.Cathepsins affect the progression of diseases by regu-lating the aggregation of abnormal proteins(e.g.α-synuclein,amyloid β-protein,huntington).Abnormal expression levels and activity and gene mutations of cathepsin B,D,and L in the nervous system can lead to the occurrence and development of neurodegenerative diseases.This review summarizes the research progress on cathepsins in neurodegenerative diseases in recent years,with a view to providing a basis for the early diagnosis and treatment of these diseases.

Objective To analyze the risk factors and the prognosis in patients with cerebral venous sinus thrombosis(CVST)accompanied by early-onset seizures.Methods A retrospective study was conducted on 163 patients with CVST admitted to the Department of Neurology and Neurosurgery of Shengjing Hospital of China Medical University during August 2011 to November 2022 as the study subjects.Based on whether they had concurrent seizures within 14 days after diagnosis CVST,the patients were divided into the early-onset seizures group(42 cases)and the non-early-onset seizure group(121 cases).Clinical data were collected,including general clinical data,imaging data,laboratory test results,and treatment plans,etc.The general clinical data involves gender,age,suspected etiology(infection[such as mastoiditis,otitis media,sinusitis,etc.],oral contraceptives/estrogen,pregnancy/puerperium,anemia and other factors that can lead to changes in blood composition,hyperhomocysteinemia),clinical manifestations(including headache,dizziness,disturbance of consciousness,nausea and vomiting,limb numbness,hemiplegia,tinnitus,aphasia,diplopia,mental abnormalities,unresponsiveness,isolated intracranial hypertension[papilledema],etc.).Imaging data includes involved venous sinus location,multiple venous sinuses(involving ≥ 2 venous sinuses)and intracranial changes(intracranial hemorrhage,venous cerebral infarction,subarachnoid hemorrhage).All patients were tested for D-dimer on the second day of admission.Patients with intracranial hypertension were examined with spinal puncture and measured cerebrospinal fluid pressure,with elevated cerebrospinal fluid pressure defined as the pressure＞180mmH2O.The patients were followed up by telephone 2 months after discharge,and the modified Rankin scale(mRS)was used to assess the prognosis of the patients(mRS score ≤2 points as good prognosis,mRS score＞2 points as poor prognosis).The mortality rate of patients was measured.The clinical data,imaging data,laboratory test results,treatment and follow-up results of the two groups were compared.The correlation variables with P＜0.05 in the univariate analysis were included in the multivariate Logistic regression model to analyze the independent risk factors of CVST accompanied by early-onset seizures.Results(1)Compared with the non-early-onset seizure group,the proportion of pregnant/puerperal females in the early-onset seizure group was higher(33.3％vs.13.2％,P=0.004),the proportion of patients with hemiplegia was higher(23.8％vs.6.6％,P=0.005),and the proportion of patients with CVST imaging combined with intracranial hemorrhage was higher(40.5％vs.13.2％,P＜0.01),with all the differences were statistically significant.There was no significant difference in other baseline clinical data between the two groups(all P＞0.05).(2)Further multivariate Logistic regression analysis showed that pregnancy/puerperium(OR,4.854,95％CI 1.917-12.290,P=0.001),hemiplegia(OR,3.871,95％CI 1.246-12.028,P=0.019)and intracranial hemorrhage(OR,5.005,95％CI 2.038-12.288,P＜0.01)were independent risk factors for CVST with early-onset seizures.(3)There were 3 patients(7.1％)in the early-onset seizure group and 6 patients(5.0％)in the non-early-onset seizure group dead,and there was no significant difference in the proportion of death between the two groups(P=0.887).The proportion of patients with good prognosis in the early-onset seizure group was lower than that in the non-early-onset epilepsy group(81.0％vs.92.6％),and the difference between the groups was statistically significant(P=0.043).Among the patients treated with anticoagulation alone,the good prognosis rate of non-early-onset seizures group(99/106,93.4％)was higher than that of the early-onset seizure group(32/40,80.0％),and the difference was statistically significant(P=0.029).Conclusions For CVST patients,especially females during pregnancy or postpartum period,clinical manifestations accompanied by hemiplegia,and with intracranial hemorrhage on imaging,the risk of seizures within 14 days of the diagnosis of CVST should be vigilant.The prognosis of CVST patients with early-onset seizures is worse than that of patients without early-onset seizures.