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.

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

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

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

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.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Humans ; Waldenstrom Macroglobulinemia ; Prospective Studies

;Aim To investigate the molecular mechanism of miR-326 inhibiting breast cancer invasion and metastasis by regulating EphB3 expression. Methods RTFQ-PCR was used to examine the expression of miR-326 in normal breast epithelial cells and breast cancer cells and the transfection efficiency of miR-326 overexpression plasmid. EdU cell proliferation assay and Transwell assay were used to examine the changes in proliferation, migration and invasion ability of different subgroups of cells. Dual luciferase assay was used to verify the presence of binding sites for miR-326 and EphB3. Western blot was used to detect the expression of EphB3 in breast cancer cells after overexpression of miR-326. Results RTFQ-PCR results showed that miR-326 was lowly expressed in breast cancer cells and successfully transfected (P < 0. 05). EdU proliferation assay and Transwell assay results showed that overexpression of miR-326 in breast cancer cells inhibited proliferation, migration and invasive ability (P < 0. 05). The results of dual luciferase assay showed that miR-326 could interact with the 3'-UTR of EphB3 (P < 0. 05). Western blot and Transwell assays showed that miR-326 could negatively regulate EphB3 to inhibit invasive metastasis of breast cancer cells (P < 0. 05). Conclusions MiR-326 acts as a cancer suppressor genes in the development of breast cancer and suppresses the invasion and metastasis of breast cancer cells by regulating the expression of EphB3.

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing>50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.
Humans ; Injections ; Medicine, Chinese Traditional ; Research Design ; Sepsis/drug therapy*

Objective To analyze the correlation between femoral head CT values in routine abdominopelvic CT scanning and hip bone mineral density(BMD)values in hip quantitative CT(QCT)measurements,and to investigate the diagnostic value of femoral head CT values for hip osteoporosis.Methods Totally 176 patients undergoing non-enhanced abdominopelvic CT scanning at some hospital from June 1,2021 to January 20,2022 were selected prospectively,and femoral head CT values and hip BMD values were measured on the scanned images.The patients were divided into a normal bone mass group,a reduced bone mass group and an osteoporosis group according to hip T values and the"China Guideline for the Diagnosis Criteria of Osteoporosis with Quantitative Computed Tomography(2018)".Analyses were carried out for the correlation between femoral head CT values and hip BMD values,the difference between femoral head CT values and BMD values of the two sides with paired t-test,the difference of CT values between the three groups with ANOVA and the diagnostic efficacy of femoral head CT values for diagnosing hip osteoporosis with AUC curve.Results The values of femoral head CT and hip BMD had a strong correlation(r=0.696),which were slightly higher on the left than on the right.The three groups had statistically significant differences of femoral head CT values at two sides(P=0.000),which were ranked according to CT values as the normal bone mass group,the reduced bone mass group and the osteoporosis group.Femoral head CT values and hip BMD values both reached the peak at the age of 41 to 50 years,and then decreased gradually.Femoral head CT values behaved well in predicting hip osteoporosis,with femoral head AUC value being 0.859 on the left and 0.846 on the right.Conclusion The values of femoral head CT and hip BMD had a strong correlation,and femoral head CT values are valuable for diagnosing osteoporosis.[Chinese Medical Equipment Journal,2023,44(9):64-68]