Objective To investigate the distribution characteristics of pathogens causing infections within 90 days after liver transplantation and the influencing factors of infection. Methods Clinical data of 176 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital Affiliated to Capital Medical University from September 2021 to August 2024 were retrospectively analyzed. Patients were divided into the infection group (n=124) and the non-infection group (n=52) based on whether they developed infection within 90 days after transplantation. The distribution characteristics of pathogens in infected patients were analyzed. Univariate and multivariate logistic regression analyses were used to explore the influencing factors of infection. Results Among the 176 liver transplant recipients, 124 cases developed 243 episodes of 518 bacterial, fungal, viral or mycoplasma infections within 90 days after transplantation, with an overall infection rate of 70.5% (124/176). The composition of pathogens was mainly Gram-negative bacteria (38.6%, 200/518), followed by Gram-positive bacteria (32.2%, 167/518) and viruses (15.4%, 80/518), and fungi accounted for 13.1% (68/518). Among Gram-negative bacteria, the main pathogen was Klebsiella pneumoniae (6.8%, 35/518), and among Gram-positive bacteria, the main pathogen was Enterococcus faecalis (8.5%, 44/518). Viruses included Epstein-Barr virus (3.7%, 19/518) and cytomegalovirus (3.7%, 19/518), and fungi were mainly Candida albicans (6.8%, 35/518). The most common infection site among the 243 episodes was pulmonary infection (42.0%, 102/243), followed by abdominal infection (22.6%, 55/243) and bloodstream infection (18.1%, 44/243). The infections mainly occurred within 2 weeks after transplantation (60.9%, 148/243). Multivariate logistic regression analysis indicated that preoperative infection within 2 weeks, a high preoperative model for end-stage liver disease (MELD) score, and preoperative sarcopenia were independent risk factors for infection within 90 days after liver transplantation (all odds ratio>1, P<0.05). After multivariate correction, the levels of CD4⁺T cells and CD8⁺T cells within 90 days after surgery were independently associated with the occurrence of infection. Low levels of CD4⁺T cells and CD8⁺T cells might be related to an increased risk of infection. Conclusions The infection rate after liver transplantation is high, and the pathogens are mainly Gram-negative bacteria. The lungs are the most common infection site. Preoperative MELD score, preoperative sarcopenia and preoperative infection within 2 weeks are independent risk factors for infection within 90 days after liver transplantation. Regular monitoring of immune indicators CD4⁺T cells and CD8⁺T cells levels after transplantation is helpful to reduce the occurrence of post-transplantation infection.

To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine，the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13，2024，the 36^th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing，focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction （ED）. The conference brought together leading experts from traditional Chinese medicine，western medicine，and interdisciplinary fields，facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED，researching and developing new drugs of traditional Chinese medicine，and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs，it identified key directions for future scientific layout and scientific research tackling： （1） Standardization of syndrome differentiation system of traditional Chinese medicine for ED. （2） Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. （3） High-quality clinical research guided by evidence-based medicine. （4） In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. （5） Clinical translation and application promotion of new drugs of traditional Chinese medicine. （6） Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction，key focus areas，expected objectives，and clinical value were further refined，along with the establishment of a scientifically sound priority funding level evaluation system. Therefore，building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine，this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management，effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout， research and development decision-making in new drugs of traditional Chinese medicine，research topic planning，and clinical guideline formulation.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective To explore the characteristics and correlation between perivascular spaces (PVS) and diffusion tensor image analysis along perivascular spaces (DTI-ALPS) index in patients with amnestic mild cognitive impairment (aMCI). Methods A retrospective study was conducted on a total of 118 participants, including cognitive normal (CN) healthy controls and aMCI patients, recruited from the Department of Neurology, Zhongshan Hospital, Fudan University from September 2020 to September 2022. All participants underwent structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). An automatic segmentation algorithm was used to quantify PVS metrics in the brain, and DTI-ALPS index was calculated based on DTI. Differences in DTI-ALPS index and PVS metrics between the CN and aMCI groups were compared. Multivariate logistic regression was used to identify independent factors influencing aMCI. Correlation analysis was performed to assess relationships among DTI-ALPS index, PVS metrics, and cognitive scores. Results A total of 80 CN healthy controls and 38 aMCI patients were included. The DTI-ALPS index was significantly lower in the aMCI group compared with the CN group (1.28±0.18 vs 1.37±0.21, P＝0.018), while differences in PVS metrics between groups were not statistically significant. Multivariate logistic regression analysis indicated that DTI-ALPS index was an independent factor affecting aMCI (OR＝0.097, 95%CI 0.011–0.833, P＝0.033). Correlation analysis revealed a positive relationship between DTI-ALPS index and MMSE score (r＝0.210, P＝0.023) as well as PVS length in the centrum semiovale (r＝0.216, P＝0.019). Conclusions The DTI-ALPS index may serve as an imaging biomarker for identifying early cognitive impairment, and patients with aMCI exhibit abnormal DTI-ALPS indices, suggesting that brain glymphatic system dysfunction may occur prior to morphological changes.

ObjectiveTo analyze the epidemiological and etiological characteristics of a cluster of human metapneumovirus (HMPV) infection in a kindergarten in Gongshu District of Hangzhou City in May 2024, and to provide reference for the prevention and control of similar outbreaks. MethodsAn on-site investigation was conducted using an epidemiological case investigation form. Throat swab specimens collected from cases were screened for 13 respiratory pathogens using real-time fluorescent polymerase chain reaction (PCR). For HMPV nucleic acid positive specimens, the F gene of HMPV was used as the target gene for amplification and sequencing. The sequencing results were then compared with sequences in GenBank database to determine the virus subtypes and perform phylogenetic analyses. ResultsThe outbreak occurred in a kindergarter junior class with a total of 28 preschoolers and 3 teachers and childcare workers. A total of 11 cases (10 preschoolers and 1 teacher) were identified, including 8 male cases and 3 female cases. Clinical manifestations included fever in all 11 cases (100.00%), cough in 8 cases (72.72%), catarrhal symptoms in 4 cases (36.36%), and headache in 3 cases (27.27%). All symptoms were mild, and no severe cases were observed. A total of 11 throat swab samples were collected. Real-time fluorescent PCR test results showed that 3 samples were positive for HMPV nucleic acid, 2 samples were positive for both HMPV and Streptococcus pneumoniae, and 1 sample was positive for both HMPV and rhinovirus. The sequences of the 6 HMPV nucleic acid positive specimens were amplified and analyzed using specific primers, and all were determined to be HMPV subtype A2b. The F gene fragment sequence showed the highest similarity to PV081665.1/Brazil/2024 (99.65%), and also exhibited high similarity to PP683455.1/Indonesia/2021 (99.48%), PV016275.1/Beijing/2024 (99.31%), and PV052230.1/USA/2024 (99.13%). ConclusionThis cluster of acute respiratory tract infection was caused by HMPV subtype A2b, with co-infection of rhinovirus and Streptococcus pneumoniae. The F gene fragment sequences of the HMPV in this outbreak were highly homologous to those of the A2b strains isolated from Brazil, Beijing, Indonesia, and the the United States.

Selenoproteins, as the active form of selenium, play an important role in various physiological and pathological processes, such as anti-oxidation, anti-tumor, immune response, metabolic regulation, reproduction and aging. Although the expression level of selenoproteins in adipose tissue is significantly influenced by dietary selenium intake, it is closely related to the homeostasis of adipose tissue. In this review, we summarized the role of selenoproteins in the physiological function of adipose tissue and the pathogenesis of obesity in recent years, in order to provide a rationale for developing potential therapeutic agents for the treatment of obesity and related metabolic diseases.
Selenoproteins/metabolism* ; Adipose Tissue/physiology* ; Obesity/metabolism* ; Humans ; Animals ; Selenium

Intervertebral disc degeneration (IDD) is the main cause of low back pain. Immune cells play an extremely important role in regulating the progression of IDD by interacting with nucleus pulposus (NP) cells and the extracellular matrix (ECM). Healthy NP tissue is a vascular-free and immune-privileged tissue that does not normally interact with macrophages. However, the establishment of neovascularization channels in damaged intervertebral discs has led to extensive cross-talk between NP and macrophages, with different results depending on microenvironmental stimuli. Based on this, this review reviewed the correlation between IDD and low back pain, summarized the source and function of macrophages, and discussed the possible regulatory mechanism between macrophages and discogenic pain. Finally, potential therapies targeting macrophages to delay IDD in recent years were also discussed, aiming to emphasize the important role of immunology in IDD and provide a new direction for the prevention and treatment of IDD.
Humans ; Intervertebral Disc Degeneration/complications* ; Macrophages/immunology* ; Low Back Pain/immunology* ; Nucleus Pulposus ; Animals ; Extracellular Matrix

Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals ; Mice ; Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Light ; Cytokines/genetics* ; Humans

OBJECTIVE: To explore the biomechanical characteristics and clinical application effects of three-dimensional (3D) printed osteotomy guide plate combined with Ilizarov technique in the treatment of rigid clubfoot. METHODS: A retrospective analysis was performed on the clinical data of 11 patients with rigid clubfoot who met the inclusion criteria and were admitted between January 2019 and December 2024. There were 6 males and 5 females, aged 21-60 years with an average of 43.2 years. Among them, 5 cases were untreated congenital rigid clubfoot, 4 cases were recurrent rigid clubfoot after previous treatment, and 2 cases were rigid clubfoot due to disease sequelae. All 11 patients first received slow distraction using Ilizarov technique combined with circular external fixator until the force lines of the foot and ankle joint were basically normal. Then, 1 male patient aged 24 years was selected, and CT scanning was used to obtain imaging data of the ankle joint and foot. A 3D finite element model was established and validated using the plantar stress distribution nephogram of the patient. After validation, the biomechanical changes of the tibiotalar joint under the same load were simulated after triple arthrodesis and fixation. The optimal correction angle of the hindfoot was determined to fabricate 3D-printed osteotomy guide plates, and all 11 patients underwent triple arthrodesis using these guide plates. The functional recovery was evaluated by comparing the American Orthopaedic Foot and Ankle Society (AOFAS) score, International Clubfoot Study Group (ICFSG) score, and 36-Item Short Form Survey (SF-36) score before and after operation. RESULTS: Finite element analysis showed that the maximum peak von Mises stress of the tibiotalar joint was at hindfoot varus 3° and the minimum at valgus 6°; the maximum peak von Mises stress of the 3 naviculocuneiform joints under various conditions appeared at lateral naviculocuneiform joint before operation, and the minimum appeared at lateral naviculocuneiform joint at neutral position 0°; the maximum peak von Mises stress of the 5 tarsometatarsal joints under various conditions appeared at the 2nd tarsometatarsal joint at hindfoot neutral position 0°, and the minimum appeared at the 1st tarsometatarsal joint at valgus 6°. Clinical application results showed that the characteristics of clubfoot deformity observed during operation were consistent with the preoperative 3D reconstruction model. All 11 patients were followed up 8-24 months with an average of 13.1 months. One patient had postoperative incision exudation, which healed after dressing change; the remaining patients had good incision healing. All patients achieved good healing of the osteotomy segments, with a healing time of 3-6 months and an average of 4.1 months. At last follow-up, the AOFAS score, SF-36 score, and ICFSG score significantly improved when compared with those before operation ( P<0.05). CONCLUSION The 3D-printed osteotomy guide plate combined with Ilizarov technique has favorable biomechanical advantages in the treatment of rigid clubfoot, with significant clinical application effects. It can effectively improve the foot function of patients and achieve precise and personalized treatment.
Humans ; Clubfoot/diagnostic imaging* ; Printing, Three-Dimensional ; Male ; Osteotomy/instrumentation* ; Female ; Ilizarov Technique/instrumentation* ; Adult ; Retrospective Studies ; Biomechanical Phenomena ; Middle Aged ; Bone Plates ; Young Adult ; Finite Element Analysis ; Treatment Outcome ; Ankle Joint/physiopathology* ; Tomography, X-Ray Computed ; External Fixators

OBJECTIVE: To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods. METHODS: Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords. RESULTS: Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc. CONCLUSION Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans ; Diabetic Foot/physiopathology* ; Biomechanical Phenomena ; Bibliometrics