Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans ; Large Language Models ; Tomography, X-Ray Computed

Kidney fibrosis is the final common pathway of virtually all chronic kidney disease (CKD). However, despite great progress in recent years, no targeted antifibrotic therapies have been approved. Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of CKD. Senescent renal tubular cells, fibroblasts, endothelial cells, and podocytes have been detected in the kidneys of patients with CKD and animal models. Nonetheless, although accumulated evidence supports the essential role of cellular senescence in CKD, the mechanisms that promote cell senescence and how senescent cells contribute to CKD remain largely unknown. In this review, we summarize the features of the cellular senescence of the kidney and discuss the possible functions of senescent cells in the pathogenesis of kidney fibrosis. We also address whether pharmacological approaches targeting senescent cells can be used to retard the the progression of kidney fibrosis.
Humans ; Cellular Senescence/physiology* ; Fibrosis ; Renal Insufficiency, Chronic/pathology* ; Kidney/pathology* ; Animals

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Poly(dimethyl siloxane)(PDMS)is suitable for the fabrication of space cell culture chips.It is necessary to perform highly stable hydrophilic modification to promote cell adhesion on PDMS surface.We modified PDMS surface by oxygen plasma treatment combining with physical adsorption in this article.PDMS,which was treated with oxygen plasma and sequentially coated with Poly-L-lysine or collagen(PLL-ox-PDMS,COL-ox-PDMS)with various solution concentration and kept in different environmental conditions,were characterized by contact angle and surface energy measurements,and atomic force microscopy(AFM).Cell growth conditions on bare PDMS and modified PDMS were compared,and the numbers of live cells cultured for 1-3 days were evaluated.Experimental results indicate that higher solution concentration and low storage temperature benefit the hydrophilicity stability.The contact angles of PLL-ox-PDMS stored in 4℃and COL-ox-PDMS were close to 60°and 65°on day 25 and 14,respectively.Both modified PDMS surfaces are suitable for cell adhesion and proliferation,and no cell layer falls offin 10 days.The modification method is especially suitable for applications such as medium and long term space cell culture.

Objective To investigate the effect of the loss of myeloid-derived growth factor(Mydgf)on the transformation of cardiac fibroblasts into myofibroblasts after myocardial infarction(MI).Methods Two adult mouse groups,including a wild-type(WT)group and another group with Mydgf knockout(Mydgf-KO),were examined in the study.The mice in these two groups were tested for their cardiac function by measuring left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(n=10).Quantitative real-time PCR(qRT-PCR)(n=3)was performed to determine the mRNA expression levels of myofibroblast markers,including α-smooth muscle actin(α-SMA),periostin(postn),type Ⅷ collagen(col8al),and connective tissue growth factor(ctgf).Western blot(n=3)was performed to verify the protein expression levels of α-SMA.MI modeling was performed on the WT and the Mydgf-KO mice.Postoperative LVEF and LVFS(n=10)were then measured.The hearts were harvested and Masson staining was performed to determine the infarcted area(n=10).The heart samples of Mydgf-KO and WT mice were collected at d 7 and d 14 after MI,respectively,to verify the expression of myofibroblast markers(n=3).Results Compared with WT mice,LVEF and LVFS in adult Mydgf-KO mice showed no significant changes(all P＞0.05).However,the mRNA levels of α-SMA and postn were upregulated,and α-SMA protein expression was also increased(all P＜0.05).After MI,compared with WT mice,LVEF and LVFS in Mydgf-KO mice decreased,and the infarcted area increased significantly(all P＜0.05).Furthermore,mRNA levels of α-SMA,col8al,postn,and ctgf were increased in Mydgf-KO mice.In addition,the α-SMA protein expression level was upregulated and α-SMA-positive fibroblasts were increased(P＜0.05).Conclusion Mydgf deletion promotes the transformation of cardiac fibroblasts into myofibroblasts and aggravates myocardial fibrosis after MI.

Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

Objective:To construct a close-loop path management model for aspiration risk screening of patients in Department of Neurosurgery, and verify its application effect in the nursing of inpatients in department of neurosurgery.Methods:Through literature retrieval and expert consultation, the close-loop path management model of aspiration risk screening was constructed. The convenient sampling method was adopted to select inpatients in the Neurosurgery Department of a ClassⅢ Grade A hospital in Jiangmen of Guangdong Province from January to December 2019. The patients admitted from January to June 2019 were set as the control group and received routine aspiration assessment and management while the patients admitted from July to December 2019 were set as the observation group and received close-loop management of aspiration risk screening. The incidences of aspiration and aspiration pneumonia were compared between the two groups.Results:In the control group, there were 506 patients, of whom 92 (18.18%) had aspiration. In the observation group, there were 543 patients, of whom 74 (13.63%) had aspiration. There was a statistically significant difference in the incidence of aspiration between the two groups (χ 2=4.078, P=0.043) . The incidence of aspiration pneumonia was 8.10% (41/506) in the control group and 5.52% (30/543) in the observation group. There was no statistically significant difference between the two groups (χ 2=2.758, P=0.097) . Conclusions:The close-loop management of aspiration risk screening standardizes the process of aspiration risk screening, guarantees the implementation of dynamic assessment and effectively reduces the incidence of aspiration, which can provide a reference for improving the management level of prevention and treatment of aspiration.

Objective To explore the clinical application value of core needle biopsy guided by fully digital mammography three-dimensional positioning system in the diagnosis of breast lesions.Methods A retrospective analysis of 21 patients who underwent guided core needle biopsy in a fully digital mammography system was performed.2 1 patients had 2 1 lesions,which included mass (4 cases),suspected calcification (15 cases)and glandular collection (2 cases)based on X-ray examination before biopsy.The needle depth was manually calculated according to the mammogram (0°and 90°),and automatically calculated with the full digital mammography three-dimensional positioning system. The needle depth was adjusted according to the combination of above two values with the patient’s skin elasticity and gland structure. After putting a small incision into the needle with local anesthesia,X-ray radiography was taken to observe the position of the puncture needle, and then the puncture gun was excited to take out the tissue at different positions of the lesion.Finally,X-ray radiography of the tissue was performed.Results 21 patients underwent biopsy with the average operation time of 45 minutes and puncture time of 25 minutes.The needle depth adjustment range was 3－5 mm,using 14G puncture needle and 4－8 pieces of tissue were pierced according to the lesions. X-ray radiographywas performed on the removed tissue strips. For all the cases of suspected calcification,the calcified lesions were found in the removed tissue strips.No serious adverse reactions occurred in 21 patients with lateral position (1 9 cases)and sitting position (2 cases).2 patients with sitting position developed dizziness, nausea,and palpitation,and recovered quickly after rest and psychological comfort.Puncture pathology confirmed 6 cases of breast cancer (1 case of intraductal papillary carcinoma,2 cases of ductal carcinoma in situ,3 cases of invasive breast cancer),and 1 5 cases of benign lesions,with no obvious changes after one year follow-up.Conclusion In the core needle biopsy guided by the fully digital mammography three-dimensional positioning system for breast lesions,the patient should be placed in the lateral position, which can effectively reduce the occurrence of adverse reactions.A 14G puncture needle and ≥4 tissue strips can achieve a higher pos-itive rate.The technology is simple and easy to perform with a high puncture accuracy,and has important application value.

Objective: To compare the clinical features, ultrasonic imaging manifestations and therapeutic evaluations between elderly onset rheumatoid arthritis (EORA) and EORA with osteoarthritis (OA). Methods: Eighty-eight patients with rheumatoid arthritis were divided into two groups: group EORA (n=36) and group EORA+OA (n=52). The onset age of all patients was 60 years or older. General conditions, joint involvement distribution, ultrasonic manifestations and disease activity scores (DAS28-3) of patients in the two groups were analyzed. The χ² test/Fisher's exact probability test and the Student's t test/Mann-Whitney U test were used to analyze data. Results: There was no significant difference in the proportion of male and female patients and erythrocyte sedimentation rate (ESR) between the two groups (P>0.05). The onset age of patients in group EORA+OA [(68±4) years old] was higher than that in group EORA [(65±4) years old], and the difference was statistically significant (t=-3.465, P=0.001). Duration of the disease and body mass index in group EORA+OA were significantly higher respectively than those in group EORA. Joint involvement in the two groups was mainly found in shoulder, wrist, Metacarpophalangeal joint (MCP)2, MCP3, proximal inter-phalangeal joint (PIP)2, PIP3, PIP4, and knee joint (34.7%-86.5%). The percentage of MCP2[36.5%(38/104), 70.8%(51/72); χ²=20.02, P<0.01], MCP3[33.7%(35/104), 59.7%(43/72); χ²=11.72, P=0.001], MCP4[4.8%(5/104), 22.2%(16/72); χ²=12.28, P<0.01], PIP2[69.2%(72/104), 83.3%(60/72); χ²=4.51, P=0.034] and PIP3[53.8%(56/104), 70.8%(51/72); χ²=5.15, P=0.023] in the EORA+OA group was lower while the percentage of MCP1, DIP 2, DIP3, DIP4 and knee joints were higher than that in the EORA group (P<0.05). In group EORA+OA, the synovial thickness of the wrist joints [(4.2±0.5) mm] and knee joints [(7.7±0.8) mm] were significantly thicker than those in group EORA [(3.2±0.9) mm; (6.3±0.8) mm, t=-5.82, P<0.01; t=-7.22, P<0.01]; The proportion (70.0%) of level 2 and 3 of patients' wrist joint synovium pannus blood flow and knee joint synovium pannus in group EORA+OA were increased than group EORA (51.9%; 52.3%), the difference between the two groups was statistically significant (χ²=4.64, P=0.031; χ²=4.43, P=0.035). There was no significant difference in DAS28-3 scores between the two groups before patients received treatment. After 2 weeks and 12 weeks of glucocorticoid treatment, DAS28-3 scores in group EORA [3.62(2.88, 4.03); 2.35(2.26, 2.62) points] were significantly lower than group EORA+OA [5.01(4.68, 5.26); 3.38(2.28, 3.83) points] (Z=-7.766, P<0.01; Z=-3.461, P<0.01). Conclusion Compared with patients of EORA alone, patients of EORA with OA have more obvious joint symptoms, MCP1, DIP and knee joint are susceptible to the co-involvement among them, longer duration of disease, and were prone to synovial hyperplasia and pannus flow formation. The therapeutic effects of glucocorticoid on joint inflammation in patients of EORA alone are superior to those patients of EORA with OA.