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.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectiveTo analyze the epidemiological characteristics of latent tuberculosis infection (LTBI) among newly detained populations in eastern China, to identify high-risk groups, and to provide a scientific basis for formulating tuberculosis prevention and control strategies in the prison system. MethodsA cross-sectional study was conducted among the newly admitted detainees in two prisons in eastern China in 2022. Data on demographic characteristics, behavioral risk factors and previous disease history of the research subjects were collected through a structured questionnaire survey. The LTBI status of the detainees was determined using the QuantiFERON-TB Gold In-Tube (QFT-GIT) method. Lasso regression was used to screen variables, followed by multivariate logistic regression analysis to investigate the influencing factors of LTBI. ResultsA total of 305 detainees were included in the study. The median age of detainees was 35 (31, 43) years. The study population was predominantly male (67.21%), of Han ethnicity (95.41%), had a junior or senior high school education (59.34%), and was unemployed (31.80%). A history of smoking was reported by 52.79% of participants, while 57.70% reported no alcohol consumption. The majority had no history of hypertension (85.90%), diabetes mellitus (93.77%), human immunodeficiency virus (HIV) infection (97.38%), familial genetic diseases (95.08%), surgery or trauma (73.77%), drug use (92.79%), or hepatitis (93.77%). The LTBI rate was 14.75%. After comparing the demographic characteristics of LTBI and non-infected groups, it was found that smoking history (χ²=7.40, P=0.025), drug use history (χ²=5.49, P=0.019), and HIV infection (χ²=8.12, P=0.004) were statistically correlated with LTBI infection. The results of multivariate logistic regression analyses showed that smoking [adjusted odds ratio (aOR)=4.08, 95%CI: 1.60‒10.42, P=0.003], HIV infection (aOR=11.57, 95%CI: 2.50‒53.51, P=0.002) and drug use (aOR=3.04, 95%CI: 1.02‒9.09, P=0.046) were risk factors for LTBI. ConclusionThe LTBI rate among newly detainees in two prisons in eastern China is slightly lower than that among long-term detainees. Early screening and intervention should be implemented for newly detainees, with particular attention focused on high-risk groups such as those with a history of smoking, HIV infection, or drug use.

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.

Objectives:To investigate the predictive value of Murray's law-based quantitative flow ratio(μQFR)in side branches for long-term clinical prognosis in patients with non-left main bifurcation lesions who underwent simple main branch stenting,and to provide a potential functional assessment standard for intervention decision-making on coronary bifurcation lesions.Methods:A retrospective analysis was conducted in 408 patients with non-left main bifurcation lesions who underwent simple main branch stenting at Lianyungang First People's Hospital and Nanjing First Hospital between July 2018 and January 2021.The study utilized third-generation QFR software to analyze pre-and post-procedure anatomical and functional parameters of the target lesion's main branch and key branches.The primary endpoint was target vessel failure(TVF)events during the 3-year follow-up.Patients were stratified into TVF and non-TVF groups.Baseline characteristics,procedural data,and pre-/post-procedural parameters of target vessels were compared between groups.Multivariable Cox regression was performed to identify predictors of TVF.Diagnostic efficacy of predictors was evaluated using area under the receiver operating characteristic(ROC)curve(AUC)with DeLong's method for comparison.Patients were dichotomized based on the optimal cutoffof post-procedural side branch μQFR,with TVF incidence rates compared via Cox regression and Kaplan-Meier analysis.Results:During 3-year follow-up,54 patients(13.2%)experienced TVF(TVF group),data were compared with 354 patients(86.76%)without TVF(non-TVF group).The TVF group showed higher post-procedural side branch diameter stenosis([32.93±17.80]%vs.[22.62±11.96]%,P<0.001)and lower μQFR(0.80±0.10 vs.0.89±0.07,P<0.001).Multivariate Cox regression identified higher post-procedural side branch μQFR as an independent protective factor against 3-year TVF(per 0.01 increase:HR=0.903,95%CI:0.850-0.959,P<0.001).ROC curves indicated that post-procedural side branch μQFR had moderate diagnostic efficacy for predicting 3-year TVF(AUC=0.769,95%CI:0.678-0.861,P<0.001),with a significantly higher AUC value than post-operative side branch area stenosis and minimal lumen diameter(both P<0.001),the optimal cutoffvalue was 0.84.Multivariate Cox regression and Kaplan-Meier survival analysis revealed markedly higher 3-year TVF rates in patients with μQFR≤0.84 compared to patients with μQFR>0.84(HR=4.007,95%CI:2.342-6.855,P<0.001;28.3%vs.7.9%,log-rank P<0.001).Conclusions:For patients with bifurcation lesions not involving the left main,the immediate post-procedural side branch μQFR could better predict 3-year TVF than anatomical indices.Maintaining post-stenting side branch μQFR>0.84 may optimize clinical outcomes when using a single-stent strategy.

Objective To analyze the relationship between the expression of ferroptosis markers in the tumor microenvironment(TME)and the prognosis of transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).Methods This prospective observational study included 100 HCC patients who received TACE treatment at Langfang Hospital of Traditional Chinese Medicine from March 2019 to June 2021 as the study subjects.The levels of 8-isoprostaglandin F2α(8-iso-PGF2α),4-hydroxy-2-nonenal(4-HNE),8-hydroxy-2'deoxyguanosine(8-OH-dG)and hepcidin in plasma were evaluated by ELISA kit at baseline(1 day before TACE),1 day after TACE and 4～8 weeks.The changes of ferroptosis related markers during TACE treatment were compared.The difference between the level of 8-iso-PGF2α,4-HNE and the baseline 1 day after TACE treatment was recorded as △8-iso-PGF2α,△4-HNE.Results Compared with the baseline,the levels of 8-iso-PGF2α and 4-HNE increased significantly and the level of hepcidin decreased significantly one day after TACE treatment,and the differences were statistically significant(t=8.03,16.29,2.92,all P<0.05).Compared with 1 day after treatment,the levels of 8-iso-PGF2α,4-HNE decreased and the level of 8-OH-dG increased at 4～8 weeks after TACE treatment,and the differences were statistically significant(t=9.12,17.17,2.63,all P<0.05).Multivariate COX analysis showed that △8-iso-PGF2α,△4-HNE and 8-iso-PGF2α 1 day after TACE treatment were independent factors affecting the overall survival after TACE(Wald χ2=5.205,13.801,6.054,all P<0.05).The survival time of patients with △4-HNE>2.01 μg/ml was significantly longer than that of patients with △4-HNE≤2.01 μg/ml(Log-rank=5.718,P=0.017),and that of patients with△8-iso-PGF2α>1.75ng/ml was sig-nificantly longer than that of patients with△8-iso-PGF2≤1.75ng/ml(Log-rank=4.163,P=0.041).Conclusion The prognosis of HCC patients who are in a state of high ferroptosis(4-HNE and 8-iso-PGF2 increased)at 1 day after TACE treatment is better,which indicate that ferroptosis mediated HCC death induced by TACE treatment.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective:To investigate the influences of long non-coding RNA metastasis-associated lung adenocarcinoma tran-script 1(lncRNA MALAT1)/miR-876-5p/forkhead box protein M1(FOXM1)axis on TNF-α-induced proliferation,apoptosis and in-flammatory response of HaCaT cells.Methods:HaCaT cells were grouped into Ct group,Model group,si-NC group,si-MALAT1 group,mimic NC group,miR-876-5p mimic group,si-MALAT1+inhibitor NC group,and si-MALAT1+miR-876-5p inhibitor group.Except for the Ct group,cells in other groups were treated with 25 μg/L TNF-α to induce the in vitro cell model of psoriasis,and after 24 hours of TNF-α induction,the corresponding transfectants were transfected for 48 hours for subsequent experiments.qRT-PCR was applied to detect the expression of MALAT1 and miR-876-5p in cells;CCK-8 method and EdU staining were applied to detect cell pro-liferation;flow cytometry was applied to detect apoptosis;ELISA method was applied to detect the levels of IL-6,TNF-α,and IL-1β in cell supernatant;Western blot was applied to detect the protein expressions of FOXM1,proliferating cell nuclear antigen(PCNA),Bcl-2-associated X protein(Bax)and B-lymphocytoma-2(Bcl-2);dual-luciferase reporter gene assay was applied to verify the rela-tionship between MALAT1 and miR-876-5p,miR-876-5p and FOXM1;and RNA pull down experiments were applied to verify the re-lationship between MALAT1 and miR-876-5p.Results:Compared with the control group,the expressions of MALAT1 and FOXM1 protein expression in the experimental group were increased,and the expression of miR-876-5p was decreased(P<0.05);compared with Ct group,the expressions of MALAT1 and FOXM1 protein expression in HaCaT cells,A450 value,EdU positive rate,the levels of IL-6,TNF-α,IL-1β,and the protein expressions of PCNA and Bcl-2 in cell supernatant in Model group increased,the expression of miR-876-5p,apoptosis rate and the protein expression of Bax were decreased(P<0.05);silencing MALAT1 or overexpressing miR-876-5p could inhibit the proliferation and inflammatory response of HaCaT cells induced by TNF-α,and promote cell apoptosis;miR-876-5p inhibitor attenuated the inhibitory effects of silencing MALAT1 on TNF-α-induced HaCaT cell proliferation and inflammatory response,and the promotion on cell apoptosis;MALAT1 targeted and regulated the miR-876-5p/FOXM1 axis.Conclusion:Silencing MALAT1 may inhibit the expression of FOXM1 by up-regulating miR-876-5p,thereby inhibiting the proliferation and inflammatory re-sponse of HaCaT cells induced by TNF-α,and promoting cell apoptosis.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective To investigate the value of pre-treatment MRI features in predicting cachexia in hepatocellular carcinoma(HCC).Methods A retrospective analysis was conducted on 399 patients with hepatocellular carcinoma,recording their pre-treatment clinical and MRI data.All patients underwent MRI plain and enhanced scan,and their weight was followed up 6 months after the MRI examination.According to the diagnostic criteria for cachexia,patients were divided into cachexia group and non-cachexia group.They were randomly divided into the training set(n=279)and the validation set(n=120).Univariable and multivariable logistic regression analyses were used to screen variables associated with cachexia in hepatocellular carcinoma and to establish a predictive model.The receiver operating characteristic(ROC)curve was used to evaluate the predictive performance of different models.The DeLong test was used to compare the AUC values of different models,and the best-performing model was used to establish a predictive nomogram for cachexia in hepatocellular carcinoma.Results Multivariable logistic regression analysis showed that serum albumin<40 g/dL,serum alpha-fetoprotein>100 ng/mL,tumor diameter>5 cm,portal vein tumor thrombus,intratumoral arterial enhancement,and arterial phase peritumoral enhancement were independent predictors of cachexia in hepatocellular carcinoma.The clinical-imaging model showed the best predictive performance,with an AUC of 0.843 in the training set and 0.854 in the validation set.Conclusion The nomogram based on MRI features can predict cachexia in hepatocellular carcinoma 6 months earlier than clinical diagnosis,which has important clinical guidance significance.