OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

ObjectiveThe Golgi apparatus serves as a central hub in the eukaryotic secretory pathway, responsible for the processing, sorting, and trafficking of proteins and lipids. In mammalian cells, the Golgi typically forms a perinuclear ribbon-like structure composed of laterally connected cisternae stacks.The maintenance of Golgi ribbon structure depends on the balance of membrane flux across multiple intracellular trafficking pathways, yet the specific contributions of distinct trafficking branches to Golgi macroscopic morphology remain elusive. In mammalian cells, the Golgi ribbon is typically organized as a perinuclear, laterally connected structure composed of stacked cisternae, and its integrity is highly dynamic and sensitive to perturbations in membrane trafficking. This study aims to elucidate the role of coat protein complex I (COPI)-mediated retrograde transport in maintaining the Golgi ribbon and to dissect the functional relationship between the transmembrane cargo receptors LEPROT/LEPROTL1 (LEPROTs) and the COPI adaptor GOLPH3. MethodsUsing siRNA interference and gene-deficient cell lines, we selectively perturbed COPI- or adaptor protein complex 1 (AP-1)-mediated trafficking pathways in HeLa cells. To quantitatively evaluate Golgi morphology, we employed a “Golgi Angle”-based measurement to assess its circumferential distribution around the nucleus. The spatial distribution of the Golgi ribbon was quantitatively analyzed using confocal microscopy, while Golgi ultrastructure and vesicle density were examined via transmission electron microscopy. Additionally, the subcellular distribution of COPI components was assessed by immunofluorescence co-localization. ResultsSelective inhibition of COPI retrograde transport significantly induced the circumferential extension of the Golgi ribbon around the nucleus, whereas blocking AP-1-mediated anterograde transport resulted in Golgi compaction, indicating opposing roles. These results suggest that different trafficking branches downstream of ARF1 exert distinct and even antagonistic effects on Golgi morphology. LEPROTs-deficient cells exhibited a Golgi extension phenotype highly consistent with COPI impairment. Furthermore, knockdown of GOLPH3 in a LEPROTs double-knockout background produced a significant additive effect on Golgi extension, suggesting that LEPROTs and GOLPH3 play non-redundant roles in regulating COPI-related trafficking processes. Mechanistically, loss of either LEPROTs or GOLPH3 led to the aberrant accumulation of COPI components at endoplasmic reticulum exit sites, accompanied by a reduction in COPI-like vesicles around the Golgi. This redistribution indicates a defect in COPI recycling between the ER-Golgi interface and the Golgi apparatus. Ultrastructural analysis revealed that Golgi cisternae in defective cells became shorter and thicker while maintaining a stable number of stacks. In parallel, the density of Golgi-associated vesicles was markedly decreased, further supporting an impairment in COPI vesicle formation or budding processes. ConclusionThis study demonstrates that active COPI retrograde transport is a critical factor in restricting the over-connection of the Golgi ribbon and maintaining its compactness. Rather than causing fragmentation, partial disruption of COPI function leads to a distinct morphological outcome characterized by Golgi ribbon extension at the light microscopy level and cisternal remodeling at the ultrastructural level. LEPROTs and GOLPH3 cooperatively promote the recycling and vesiculation of COPI components, thereby imposing a structural constraint on the Golgi periphery. Our findings support a model in which multiple adaptor proteins act in parallel to sustain efficient COPI cycling, thereby maintaining Golgi structural homeostasis. These findings provide new cell biological evidence for the membrane trafficking basis of Golgi morphological homeostasis.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

ObjectiveTo explore the clinical efficacy of Juanbitang hot compress pack combined with intensive rehabilitation training in stroke patients with hemiplegia. MethodsA total of 80 stroke patients with hemiplegia were selected and assigned into a control group （40 cases） and an observation group （40 cases） according to the random number table method. The control group received conventional rehabilitation training and nursing intervention，while the observation group was additionally treated with Juanbitang hot compress pack. The two groups were compared in terms of the neurological function （national institute of health stroke scale score，NIHSS score），muscle strength，motor function （fugl-meyer assessment scale score，FMA score），daily living activity （modified barthel index，MBI），balance ability （berg balance scale score，BBS score），trunk control ability （Sheikh Trunk Control Test score，Sheikh TCT score），and homocysteine （Hcy） level before and after treatment. ResultsAfter treatment，the observation group had lower NIHSS score and Hcy level than the control group （P<0.05）. The total response rate of the observation group （97.50%） was higher than that of the control group （77.50%）. The scores of upper limb and lower limb FMA，MBI，BBS，and Sheikh TCT in the observation group were all higher than those in the control group （P<0.05）. ConclusionThe application of Juanbitang hot compress pack combined with rehabilitation training can effectively improve the neurological function，muscle strength，motor function，daily living ability，balance ability，and trunk control ability and reduce the Hcy level in stroke patients with hemiplegia，demonstrating enhanced clinical efficacy.

ObjectiveTo explore the association between metabolic score for visceral fat（METS-VF） and cardiometabolic multimorbidity（CMM） as well as cognitive function in the elderly population， revealing the role of METS-VF as an assessment tool in this population， and providing evidence and new perspectives for the early screening and intervention strategies of CMM and cognitive function. MethodsThis study is based on cross-sectional data from the Hubei memory and aging cohort study（HMACS）， which includes elderly individuals aged 60 and above. The METS-VF index was calculated and divided into quartiles（Q1-Q4）. CMM was assessed through a questionnaire， defining CMM as the coexistence of at least two of the following conditions： diabetes， heart disease， and stroke. Standardized cognitive tests were used to evaluate overall cognition， memory， language， executive function， and attention. Logistic and Linear regression analysis was performed to explore the association between METS-VF and the risk of CMM as well as cognitive function. A restricted cubic spline was used to test the dose-response relationship， and subgroup analysis was conducted to assess the variation of METS-VF in different populations. Additionally， multinomial unordered logistic regression was used to evaluate the performance of METS-VF in predicting CMM morbidity patterns. ResultsA total of 3 790 elderly participants aged 60 and above were included. After adjusting for confounding factors， compared with the lowest quartile（Q1）， the Q4 group of METS-VF was associated with a higher risk of CMM ［OR=3.00，95%CI （2.18， 4.16）］， and with lower scores in overall cognition ［b=-0.12， 95%CI （-0.21，-0.04）］， attention ［b=-0.14， 95%CI （-0.24，-0.05）］， and executive function ［b=-0.10， 95%CI （-0.20，-0.00）］. Dose-response analysis did not show a nonlinear relationship between METS-VF and either CMM or cognitive function （P for nonlinear > 0.05）. Subgroup analysis revealed that the male group with higher METS-VF had lower overall cognitive scores， while the female group showed lower executive function scores （P for interaction ＜ 0.05 for both）. Multinomial unordered logistic regression analysis indicated that the METS-VF index was associated with an increased risk of diabetes with coronary heart disease ［OR=2.62，95%CI （1.66， 4.15）］ or concomitant stroke ［OR=2.66，95%CI （1.73， 4.09）］， especially in the group with both diabetes and stroke and coronary heart disease， where the association between METS-VF and the risk was strongest. ConclusionsAn increased METS-VF is associated with a higher risk of CMM and lower scores in overall cognition， attention， and executive function in the elderly population. Diabetes may be a key driving factor in the multimorbidity model. The METS-VF index can serve as a dual-purpose tool for screening cardiovascular metabolic risks and assessing cognitive function.

This article reports a 14-year-old boy who presented with "a nearly 7-year history of a right upper arm mass and a more than 1-year history of cervical lymphadenopathy". His main clinical manifestations included a subcutaneous mass in the right upper arm, bilateral eyelid and submandibular masses, and multiple enlarged cervical lymph nodes, accompanied by persistent peripheral blood eosinophilia. Biopsies of the right upper arm lesion and a left submandibular lymph node showed lymphoid hyperplasia with prominent eosinophilic infiltration, vascular and fibrous tissue proliferation, and eosinophilic microabscess formation in the left submandibular lymph node, confirming the diagnosis of Kimura′s disease. The lesions regressed markedly after glucocorticoid therapy but recurred after treatment discontinuation. Because the patient and his family were concerned about long-term glucocorticoid therapy, mepolizumab was subsequently administered. Peripheral eosinophil counts normalized, whereas the local tissue lesions showed limited improvement. A multidisciplinary team comprehensively evaluated the diagnosis, the need for repeat biopsy of atypical lymph nodes on imaging, the possible association between the cardiac valve abnormalities and the underlying disease, and subsequent treatment options. The patient is currently receiving methotrexate with folic acid supplementation and remains under regular follow-up. This case indicates that the diagnosis of Kimura′s disease relies on clinical manifestations and histopathological findings. Once diagnosed, comprehensive evaluation, individualized treatment, and long-term management should be implemented.

BACKGROUND:Exosomes derived from mesenchymal stem cells play pivotal roles in cell communication and epigenetic regulation due to their low immunogenicity and targeted delivery effects,and have been clinically applied in the treatment of various diseases.OBJECTIVE:To review the isolation,purification,identification methods,and application progress of mesenchymal stem cell-derived exosomes,and to facilitate the development of large-scale preparation techniques and clinical translation of mesenchymal stem cell-derived exosomes.METHODS:The Chinese search terms"exosome,mesenchymal stem cells,isolation,purification,characterization,clinical application"and the English search terms"exosome,extracellular vesicles,mesenchymal stem cells,isolation,characterization,application"were used to search the literature published before September 2024 in CNKI,PubMed,and Web of Science databases.Articles with poor relevance to the topic,outdated,or duplicated content were excluded,and finally,109 articles were included for review.RESULTS AND CONCLUSION:(1)This paper reviews recent methods for isolating and purifying exosomes,comparing the characteristics of ultracentrifugation,ultrafiltration,size-exclusion chromatography,polymer precipitation,immunoaffinity,microfluidic methods,and other novel approaches based on their underlying principles.(2)Methods for identifying exosomes can be categorized into physical and biochemical analyses,characterizing exosomes based on their shape,size,and characteristic proteins.(3)Mesenchymal stem cell-derived exosomes have broad applications in multiple fields such as medical aesthetics,wound repair,and cancer treatment,due to their immune-regulatory properties and ability to cross biological barriers.(4)The clinical translation of exosomes faces challenges due to their complex structure,lack of universal isolation techniques,and poor stability,making it difficult to achieve in a short period of time.

BACKGROUND:Exosomes derived from mesenchymal stem cells play pivotal roles in cell communication and epigenetic regulation due to their low immunogenicity and targeted delivery effects,and have been clinically applied in the treatment of various diseases.OBJECTIVE:To review the isolation,purification,identification methods,and application progress of mesenchymal stem cell-derived exosomes,and to facilitate the development of large-scale preparation techniques and clinical translation of mesenchymal stem cell-derived exosomes.METHODS:The Chinese search terms"exosome,mesenchymal stem cells,isolation,purification,characterization,clinical application"and the English search terms"exosome,extracellular vesicles,mesenchymal stem cells,isolation,characterization,application"were used to search the literature published before September 2024 in CNKI,PubMed,and Web of Science databases.Articles with poor relevance to the topic,outdated,or duplicated content were excluded,and finally,109 articles were included for review.RESULTS AND CONCLUSION:(1)This paper reviews recent methods for isolating and purifying exosomes,comparing the characteristics of ultracentrifugation,ultrafiltration,size-exclusion chromatography,polymer precipitation,immunoaffinity,microfluidic methods,and other novel approaches based on their underlying principles.(2)Methods for identifying exosomes can be categorized into physical and biochemical analyses,characterizing exosomes based on their shape,size,and characteristic proteins.(3)Mesenchymal stem cell-derived exosomes have broad applications in multiple fields such as medical aesthetics,wound repair,and cancer treatment,due to their immune-regulatory properties and ability to cross biological barriers.(4)The clinical translation of exosomes faces challenges due to their complex structure,lack of universal isolation techniques,and poor stability,making it difficult to achieve in a short period of time.

BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

Objective: This study aims to investigate the anatomical relationship among the nerve roots, intervertebral space, pedicles, and intradural rootlets of the cervical spine for improving operative outcomes and exploring neuroventral decompression approach in posterior endoscopic cervical discectomy (PECD). Methods: Cervical computed tomography myelography imaging data from January 2021 to May 2023 were collected, and the RadiAnt DICOM Viewer Software was employed to conduct multiplane reconstruction. The following parameters were recorded: width of nerve root (WN), nerve root-superior pedicle distance (NSPD), nerve root-inferior pedicle distance (NIPD), and the relationship between the intervertebral space and the nerve root (shoulder, anterior, and axillary). Additionally, the descending angles between the spinal cord and the ventral (VRA) and dorsal (DRA) rootlets were measured. Results: The WN showed a gradual increase from C4 to C7, with measurements notably larger in men compared to women. The NSPD decreased gradually from the C2–3 to the C5–6 levels. However, the NIPD showed an opposite level-related change, notably larger than the NSPD at the C4–5, C5–6, and C7–T1 levels. Furthermore, significant differences in NIPD were observed between different age groups and genders. The incidence of the anterior type exhibited a gradual decrease from the C2–3 to the C5–6 levels. Conversely, the axillary type exhibited an opposite level-related change. Additionally, the VRA and DRA decreased as the level descended, with measurements significantly larger in females. Conclusion A prediction of the positional relationship between the intervertebral space and the nerve root is essential for the direct neuroventral decompression in PECD to avoid damaging the neural structures. The axillary route of the nerve root offers a safer and more effective pathway for performing direct neuroventral decompression compared to the shoulder approach.