Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

P-glycoprotein(P-gp)is an ATP-dependent efflux transporter that is distributed in many tissues and organs.P-gp can selectively pump endogenous substrates and exogenous chemicals from the cell to the outside of the cell to maintain a stable endo-environment.However,it meanwhile restricts the entry of therapeutic drug into tissues and organs,and in particular,mediates the multidrug resistance of tumor cells to chemotherapeutic drugs.Therefore,understanding the localization of P-gp in different tissues and organs may be an important breakthrough point for disease treatment.In this paper,we mainly review the molecular structure,transport mechanism,localization,and regulation of P-gp in different tissues and organs,providing reference for the subsequent treatment of diseases.
Humans ; ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry* ; Animals ; Drug Resistance, Multiple

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective To analyze the characteristics and differences of gut flora in patients with osteoporosis of different traditional Chinese medicine(TCM)syndrome types,thus to find out new therapeutic targets for the treatment of osteoporosis.Methods The clinical data and fecal samples of 57 patients with osteoporosis recruited in the Department of Osteoporosis,the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from February 2023 to November 2023 were collected.The patients were differentiated as the TCM syndrome types of spleen and kidney yang deficiency group(22 cases),liver and kidney yin deficiency group(18 cases)and kidney deficiency and blood stasis group(7 cases).The differences in the structure and abundance of gut flora in patients with the above three TCM syndrome types were analyzed by16S rDNA sequencing technique.Results The results of Alpha(α)diversity showed that there were no significant differences in species richness,evenness and diversity of gut flora among the three groups(P＞0.05).Beta(β)diversity analysis showed that there were significant differences in gut flora among the three groups(P=0.011).At the phylum level,Bacteroidota,Firmicutes and Proteobacteria were the top three kinds of gut flora with the highest proportion in the three groups.At the genus level,the relative abundance of Bacteroides,Escherichia-Shigella,and Faecalibacterium was higher in the group of liver and kidney yin deficiency and in the group of kidney deficiency and blood stasis,while the group of spleen and kidney yang deficiency has a large proportion of other bacteria.Conclusion There exist differences in the composition of gut flora among patients with different TCM syndrome types,and the differences are shown at the level of phylum and genus.The results indicate that gut flora may be the targets in the TCM prevention and treatment of osteoporosis.

Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Integrated medical courses are one of the key models for the development and transformation of modern medical education. Modular-based integrated courses set higher standards for knowledge, skills and quality objectives. This article primarily discusses the specific practices of teaching reform in the integrated medical course of Frontiers of Infection and Immunity for eight-year program at Air Force Medical University. It covers the selection and integration of teaching content, innovative application of various teaching methods, diversified teaching evaluation and feedback, and the teaching team building. The course not only deepens students' knowledge and promotes their creative abilities but also enhances their comprehensive literacy and international perspective, thus effectively preparing high-quality medical talents for future challenges in the medical field.
Humans ; Education, Medical/methods* ; Teaching ; Curriculum ; Immunity ; Infections/immunology*

Objective:To explore the clinical features of immunocompetent primary central nervous system lymphoma (PCNSL) and influencing factors for prognosis of immunocompetent patients with PCNSL.Methods:A retrospective analysis was performed; 69 immunocompetent patients with PCNSL confirmed by pathology in First Medical Center of PLA General Hospital from January 2016 to January 2024 were enrolled; initial symptoms, Eastern Cooperative Oncology Group (ECOG) score, and results of laboratory and pathological examinations in these patients were collected. Patients were divided into biopsy confirmed group ( n=43) and lesion resection confirmed group ( n=26) according to different diagnostic methods; patients were also divided into chemotherapy group ( n=48), chemotherapy+radiotherapy group ( n=9) and surgical resection group ( n=12) according to different treatment methods. Clinical outcomes of these patients in different groups at the end of follow-up were compared, and the influencing factors for short-term prognosis (6 months after treatment) were identified. All patients were followed up for 12.80 (6.00, 36.40) months. The short-term prognosis was evaluated by modified Rankin scale (mRS) 6 months after treatment (mRS scores of 0-2: good prognosis; mRS scores of 3-6: poor prognosis). Overall survival (OS) was recorded at the end of follow-up. Results:Among the 69 immunocompetent patients with PCNSL, 37 were males and 32 were females; median onset age was 59 years, ranged 24-83 years. Focal neurologic deficits of different degrees (34/69, limb weakness, sensory disturbances, ataxia, or eye involvement) were the most common initial symptoms, followed by headache (14/69), dizziness (10/69), cognitive dysfunction (9/69), epilepsy (1/69) and psychiatric disorders (1/69). Forty-five patients underwent cerebrospinal fluid examination: 17 had cerebrospinal fluid pressure≥200 mmH 2O (1 mmH 2O=9.8 Pa); 10 had increased white blood cell count (>10×10 6/L), reaching to (16.5[11.0, 20.0])×10 6/L; 32 had increased protein level, reaching to 758.10 (547.83, 948.13) mg/L. Cerebrospinal fluid cytology was performed in 15 patients, and tumor cells were found in only 1 patient. Cranial MRI showed that intracranial solitary lesions were more common (60.87%, 42/69), and most lesions were at the basal ganglia region (40.58%, 28/69). PET/CT showed a obviously higher metabolism of the lesions (97.06, 33/34), with maximum standardized uptake of 22.9 (13.9, 30.55) g/mL. All patients had diffuse large B-cell lymphoma (DLBCL). By the end of follow-up, 28 patients died. Logistic regression analysis showed that ECOG score≥2 ( OR=9.210, 95% CI: 2.558-32.896, P=0.001) and positive MYC ( OR=0.088, 95% CI: 0.008-0.973, P=0.047) were independent risk factors for poor short-term prognosis. Cox proportional hazard regression model analysis showed that ECOG score≥2 ( HR=5.135, 95% CI: 2.230-11.827, P<0.001), positive B-cell lymphoma 6 (BCL-6, HR=0.226, 95% CI: 0.079-0.649, P=0.006) and chemotherapy or chemotherapy+radiotherapy ( HR=0.392, 95% CI: 0.157-0.980, P=0.045) were independent prognostic factors for OS. Conclusions:In immunocompetent patients with PCNSL, focal neurological deficits are more common at the onset, and fever is rare. Patients with ECOG score≥2 are more likely to have poor short-term prognosis and short OS. MYC-positive patients will have a better short-term prognosis; BCL-6 positive patients and patients treated with chemotherapy or chemotherapy+radiotherapy will have longer OS.

Objective:To explore the clinical features of immunocompetent primary central nervous system lymphoma (PCNSL) and influencing factors for prognosis of immunocompetent patients with PCNSL.Methods:A retrospective analysis was performed; 69 immunocompetent patients with PCNSL confirmed by pathology in First Medical Center of PLA General Hospital from January 2016 to January 2024 were enrolled; initial symptoms, Eastern Cooperative Oncology Group (ECOG) score, and results of laboratory and pathological examinations in these patients were collected. Patients were divided into biopsy confirmed group ( n=43) and lesion resection confirmed group ( n=26) according to different diagnostic methods; patients were also divided into chemotherapy group ( n=48), chemotherapy+radiotherapy group ( n=9) and surgical resection group ( n=12) according to different treatment methods. Clinical outcomes of these patients in different groups at the end of follow-up were compared, and the influencing factors for short-term prognosis (6 months after treatment) were identified. All patients were followed up for 12.80 (6.00, 36.40) months. The short-term prognosis was evaluated by modified Rankin scale (mRS) 6 months after treatment (mRS scores of 0-2: good prognosis; mRS scores of 3-6: poor prognosis). Overall survival (OS) was recorded at the end of follow-up. Results:Among the 69 immunocompetent patients with PCNSL, 37 were males and 32 were females; median onset age was 59 years, ranged 24-83 years. Focal neurologic deficits of different degrees (34/69, limb weakness, sensory disturbances, ataxia, or eye involvement) were the most common initial symptoms, followed by headache (14/69), dizziness (10/69), cognitive dysfunction (9/69), epilepsy (1/69) and psychiatric disorders (1/69). Forty-five patients underwent cerebrospinal fluid examination: 17 had cerebrospinal fluid pressure≥200 mmH 2O (1 mmH 2O=9.8 Pa); 10 had increased white blood cell count (>10×10 6/L), reaching to (16.5[11.0, 20.0])×10 6/L; 32 had increased protein level, reaching to 758.10 (547.83, 948.13) mg/L. Cerebrospinal fluid cytology was performed in 15 patients, and tumor cells were found in only 1 patient. Cranial MRI showed that intracranial solitary lesions were more common (60.87%, 42/69), and most lesions were at the basal ganglia region (40.58%, 28/69). PET/CT showed a obviously higher metabolism of the lesions (97.06, 33/34), with maximum standardized uptake of 22.9 (13.9, 30.55) g/mL. All patients had diffuse large B-cell lymphoma (DLBCL). By the end of follow-up, 28 patients died. Logistic regression analysis showed that ECOG score≥2 ( OR=9.210, 95% CI: 2.558-32.896, P=0.001) and positive MYC ( OR=0.088, 95% CI: 0.008-0.973, P=0.047) were independent risk factors for poor short-term prognosis. Cox proportional hazard regression model analysis showed that ECOG score≥2 ( HR=5.135, 95% CI: 2.230-11.827, P<0.001), positive B-cell lymphoma 6 (BCL-6, HR=0.226, 95% CI: 0.079-0.649, P=0.006) and chemotherapy or chemotherapy+radiotherapy ( HR=0.392, 95% CI: 0.157-0.980, P=0.045) were independent prognostic factors for OS. Conclusions:In immunocompetent patients with PCNSL, focal neurological deficits are more common at the onset, and fever is rare. Patients with ECOG score≥2 are more likely to have poor short-term prognosis and short OS. MYC-positive patients will have a better short-term prognosis; BCL-6 positive patients and patients treated with chemotherapy or chemotherapy+radiotherapy will have longer OS.

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*