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.

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

Objective To observe the clinical efficacy of Shuangye San(the prescription mainly composed of Mori Folium and Nelumbinis Folium)in the treatment of type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)of spleen deficiency and phlegm stasis type.Methods A total of 80 patients with T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type were randomly divided into a treatment group and a control group,with 40 cases in each group.The control group was treated with conventional western medicine for lowering blood glucose and lipid,protecting liver and lowering enzymes.The treatment group was treated with the granules of Shuangye San orally on the basis of treatment for the control group.The course of treatment lasted for three months.The changes of traditional Chinese medicine(TCM)syndrome scores,homeostasis model assessment of insulin resistance(HOMA-IR),fasting insulin(FINS),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1C),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),liver function indicators and B-ultrasound grading of fatty liver in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 85.00％(34/40),and that of the control group was 70.00％(28/40).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the scores of TCM symptoms of obese physique,heaviness and weakness in the limbs,shortness of breath and unwilling to talk,tightness and stabbing pain in the chest,abdominal distension and poor appetite in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the levels of glucose and lipid metabolism indicators of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the level of HDL-C was significantly increased compared with that before treatment(P＜0.05).The decrease of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C levels and the increase of HDL-C levels in the treatment group were significantly superior to those in the control group(P＜0.05).(4)After treatment,the levels of liver function indicators of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and gamma-glutamyl transpeptidase(GGT)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of liver function indicators in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the B-ultrasound grading of fatty liver of the two groups was significantly improved compared with that before treatment(P＜0.05),and the improvement of fatty liver B-ultrasound grading in the treatment group was significantly superior to that in the control group,and the difference was statistically significant(P＜0.05).(6)During the treatment,there were no adverse reactions such as impairment of liver and kidney function and abnormalities in routine blood,urine and stool test in the two groups.Conclusion Shuangye San exerts certain effect in the treatment of T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type.It can alleviate the clinical symptoms of patients,correct the disorder of glucose and lipid metabolism,and improve liver function and fatty liver B-ultrasound grading.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.