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

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective:To investigatethe heterogeneity of career growth recognition amongphysicians at the stage of standardized training and the growth characteristics of clinical physicians in the early stage, and to provide a reference for improving the quality of standardized training.Methods:The trainees who received standardized residency trainingwere randomly selected from three grade A tertiary hospitals in Chongqing, China. Mplus7.4 was used for latent profile analysis to explain the relationship between explicit continuous indicators, and the subtypes of career growth recognition were analyzed.Results:Career growth recognition at the stage of standardized training was classifiedinto three subtypes of all-round growth recognition, high resource and expectation recognition, and unclassified growth recognition, among which the subtype of unclassified growth recognition accounted for the highest percentage of 40.27% (207 trainees).Conclusions:Physicians at the stage of standardized training show obvious uncertainty aboutcareer growth recognition, and it is necessary to strengthen the education on career growth recognition during standardized training and design a development pathway based on the characteristics of career growth recognition.

Objective:To explore the clinical application value of pre-breathing mode in double-low imaging of 320-slices computed tomography(CT)for pulmonary artery.Methods:A total of 100 patients who underwent CT pulmonary angiography(CTPA)for suspected pulmonary embolism(PE)in Liuzhou People's Hospital from July 2021 to September 2022 were prospectively selected as the research subjects and they were randomly divided into observation group and control group,with 50 cases in each group.The patients of the control group adopted conventional breathing mode(the breathing password was activated after reaching the threshold,and the scan was triggered after 6 s),while the patients of the observation group adopted the pre-breathing mode(the breathing password was activated after 1 or 2 seconds,and the scan was triggered after reaching the threshold).Both two groups adopted double low-technique scan of 320 slices CT.The differences in delay time,radiation dose,the points of subjective and objective image quality,and other indicators were compared between the two groups.Results:The volume CT dose index(CTDIvol),dose length product(DLP),effective dose(ED)and delay time of the observation group were significantly lower than those of the control group(t=76.230,30.225,12.282,7.088,P<0.05),respectively.The comparison of the subjective points of image qualities between the two groups indicated that there were 25 cases with 5 points,23 cases with 4 points and 2 cases with 3 points in the observation group,and there were 21 cases with 5 points,26 cases with 4 points and 3 cases with 3 points in the control group.There was no significant difference in the averagely subjective points of image qualities between two groups(P>0.05).The signal-to-noise ratio(SNR)and signal to noise ratio(CNR)of the observation group were significantly lower than those of the control group,and the noise level(SD)of the observation group was significantly higher than that of the control group(t=25.441,23.886、11.426,P<0.05),respectively.The CT values of the artery trunk of right pulmonary,artery branch of right pulmonary,artery trunk of left pulmonary and artery branch of left pulmonary in the observation group were significantly higher than those in the control group(t=2.256,2.225,2.042,2.277,P<0.05),respectively.Conclusion:The pre-breathing mode can effectively improve CTPA image quality,and reduce radiation dose and the dosage of contrast agent,which clinical application effect is significant.It is worth learning.

Objective:To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023.Methods:An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University′s HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis.Results:A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 +T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4 +T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion:The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 +T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

Objective:To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023.Methods:An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University′s HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis.Results:A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 +T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4 +T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion:The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 +T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

Objective    To explore the treatment outcome of carotid endarterectomy combined with vertebral artery transposition in patients with severe stenosis to occlusion of the vertebral artery V1 segment and the ipsilateral carotid artery. Methods    From June 2017 to September 2020, patients with severe stenosis to occlusion of the vertebral artery V1 segment and the ipsilateral carotid artery treated with carotid endarterectomy combined with vertebral artery transposition in Fuwai Hospital were retrospectively analyzed. Results    Finally 12 patients were enrolled, including 10 males and 2 females with an average age of 67.8±6.0 years. Twelve patients were successfully operated and the follow-up time was 1-3 years. The stenosis degree of the V1 segment of the vertebral artery decreased from 83.5%±11.8% to 24.9%±14.3% (P<0.001). The stenosis degree of carotid artery decreased from 85.6%±11.0% to 0% (P<0.001). Postoperative follow-up showed that the symptoms of symptomatic patients before surgery improved. The 1-year and 3-year patency rates were 100.0%, and there were no peripheral nerve injury complications, perioperative deaths or strokes. Conclusion    Carotid endarterectomy combined with vertebral artery transposition can treat ipsilateral carotid artery  stenosis and vertebral artery stenosis at the same time, improve blood supply to the brain, improve patients' symptoms and has high promotion value.

【Objective】 To study the effect of perioperative allogeneic blood transfusion on patients with oral squamous cell carcinoma (OSCC) after first-stage free flap transplantation. 【Methods】 A total of 306 OSCC patients who accepted primary repair and reconstruction using free flap admitted to our affiliation from January 2010 to January 2019 were selected as the research objects and retrospectively analyzed. According to their clinical data, they were divided into three groups: no transfusion group (n=98), 1-2 U transfusion group (n=131) and 3 + U transfusion group (n=77), respectively. The incidence of complications including flap infection, blood circulation disorder and hematoma in the three groups were compared. The five-year survival rate of the three groups was calculated by Kaplan-Meier analysis, and the relative risk of death was analyzed by Cox regression. 【Results】 There was no statistically significant difference among the three groups of patients (P>0.05) regarding such baseline data as embracing gender, age, primary location, degree of differentiation, adjuvant radiotherapy and chemotherapy. The complication rate of patients with 3 + U transfusion (25.97%) was significantly higher than that of no transfusion (6.12%) and 1-2 U transfusion (10.86%) (P<0.05); and the five-year survival rate of patients with 3 + U transfusion (51.95%) was significantly lower than that of no transfusion (69.38%) and 1-2 U transfusion (62.60%) (P<0.05). The results of univariate analysis showed that age, adjuvant radiotherapy, degree of tissue differentiation, collateral infiltration, vascular invasion and blood transfusion were all factors influencing the quality of prognosis after repair and reconstruction of first-stage free flap transplantation treating OSCC (P<0.05). The results of multivariate analysis showed that adjuvant chemoradiotherapy was an independent protective factor for the prognosis and survival quality of postoperative OSCC patients (P<0.01); the degree of differentiation, vascular invasion and blood transfusion were independent risk factors for the prognosis and survival quality of postoperative OSCC patients (P<0.05). 【Conclusion】 Perioperative allogeneic transfusion in OSCC patients can increase the risk of postoperative complications and directly affect their prognostic quality. It can be regarded as an important risk factor for OSCC patients.

Objective    To investigate the treatment of modified vertebral-carotid transposition (VCT) in patients with severe stenosis or occlusion at V1 segment of vertebral artery. Methods    A retrospective study of 13 patients with severe stenosis or occlusion at V1 segment of vertebral artery treated by modified VCT in our hospital from October 2016 to December 2018 was done. There were 10 males and 3 females with an average age of 70.5±7.1 years. Results    The operation was successful in this series of patients. The follow-up duration was 1-3 years. The stenosis degree of the V1 segment of the vertebral artery decreased from 86.8%±7.5% to 17.4%±14.5%. All patients achieved remission of symptoms after the surgery. Temporary peripheral nerve injury occurred in 6 patients. Four patients with neurological complications relieved during follow-up. The patency rate was 100.0% at postoperative 1 and 3 years. There was no perioperative death, stroke or re-intervention. Conclusion    Modified VCT can precisely restore the distal blood flow of patients with severe stenosis or occlusion at V1 segment of vertebral artery, and relieve their symptoms.