1.Advancements in Gas-releasing Micro/Nanoplatforms for Overcoming MDR Bacterial Infections in Diabetic Wounds
Ruo-Can LIU ; Yu-Qian WANG ; Shuai ZHANG ; Shao-Zhi ZUO ; Yun-Di WU ; Xi-Long WU
Progress in Biochemistry and Biophysics 2026;53(5):1356-1375
Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H2S significantly accelerates endothelial cell migration for neovascularization, and H2 acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.
2.Advancements in Gas-releasing Micro/Nanoplatforms for Overcoming MDR Bacterial Infections in Diabetic Wounds
Ruo-Can LIU ; Yu-Qian WANG ; Shuai ZHANG ; Shao-Zhi ZUO ; Yun-Di WU ; Xi-Long WU
Progress in Biochemistry and Biophysics 2026;53(5):1356-1375
Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H2S significantly accelerates endothelial cell migration for neovascularization, and H2 acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.
3.Bioequivalence study of desloratadine tablets in healthy Chinese subjects
Peng-fei XIE ; Yuan-lu CHEN ; Hong-di CUI ; Hui LONG ; Yong-gang ZHAO ; Qi-shan HUANG ; Peng YANG ; Yan ZHOU ; Yong-dong ZHANG
The Chinese Journal of Clinical Pharmacology 2025;41(2):220-224
Objective To explore the pharmacokinetic(PK)characteristics of desloratadine tablets and reference drugs in healthy subjects,and evaluate their bioequivalence and safety.Methods The random,open,two-period,cross-over pharmacokinetic study method was adopted,each subject received a single oral dose of desloratadine tablets test drug(T)or reference drug(R)for 5 mg.The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS);and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main PK parameters of T and R of desloratadine were as follows:the fasting condition Cmax were respectively(3 809.82±1 016.54)and(3 642.36±777.07)pg·mL-1;AUC0-120h were respectively(5.75 ×104±5.03 ×104)and(5.51 × 104±4.00 × 104)pg·h·mL-1;AUC0-∞ were respectively(6.85× 104±1.03× 104)and(6.37 × 104±7.92 × 104)pg·h·mL-1.The fed condition Cmax were respectively(4 398.98±1 191.22)and(4 744.4±1 511.97)pg·mL-1;AUC0-120h were respectively(5.25 × 104±1.82 × 104)and(5.55 × 104±1.98 × 104)pg·h·mL-1;AUC0-∞ were respectively(5.37 × 104±1.86 × 104)and(5.68 × 104±2.04 × 104)pg·h·mL-1.The 90%confidence interval of Cmax,AUC0-t and AUC0-∞ of desloratadine were all within 80.00%~125.00%.Conclusion There was no significant difference in the main PK parameters between T tablets and R under fasting or high-fat postprandial conditions,and desloratadine tablets were bioequivalent,safe and well tolerated.
4.Construction and identification of a sizeable naive human Fab phage display antibody library
Yakun ZHAO ; Xiaoyue WEI ; Fanliang MENG ; Wentao LIU ; Jiaming FAN ; Lijin LONG ; Wanting WANG ; Jianling CHEN ; Jianzhong ZHANG ; Lihua HE ; Liyong LIU ; Rui ZHAO ; Di SUN ; Xuezhen YUAN ; Xiaomei YAN
Chinese Journal of Epidemiology 2025;46(2):288-295
Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.
5.Application of the Anderson sampler in the inspection for the filtration efficiency for bacteria in medical mask
Di LEI ; Chen WANG ; Minjuan ZHANG ; Cunlin LONG ; Jian REN ; Zhijie ZHAO ; Yuwei LI ; Yun LING ; Xiaoning SUN ; Jing ZHAO
China Medical Equipment 2025;22(3):160-163
The medical mask,which is used as an important tool of preventing the spread of respiratory diseases,can effectively block the transmission of biological aerosols.The detection for the filtration efficiency of bacteria in medical mask is particular importance.The Andersen sampler,is one kind of device that samples microbial aerosols,is widely used in the inspection for the filtration efficiency for bacteria in medical masks.It mainly consists of six impactors with different pore sizes.It simulates the deposition process of the most of particles at different positions in respiratory system through the bacterial particles in biological aerosols impact respectively the surface of petri dishes with agar under different pore sizes.This paper explored the development background,structure and sampling principle,operation and counting procedures of the Andersen sampler,as well as its application and importance in the inspection for the filtration efficiency for bacteria in medical mask.
6.Performance verification of fully automated chemiluminescence immunoassay analyzer in measuring special sequence indicators of serum β-CTx
Di LEI ; Jian REN ; Minjuan ZHANG ; Xiaoning SUN ; Yingjun LI ; Xiaodong ZHANG ; Cunlin LONG
China Medical Equipment 2025;22(8):57-60
Objective:To verify the performance of MAGLUMI 4000 fully automatic chemiluminescence immunoassay analyzer in measuring special sequence of β-Collagen(β-CTx).Methods:Referring to a series of standards included WS/T 492-2016"Verification of performance for precision and trueness of quantitative measurements in clinical laboratories"and CNAS-GL037 2019"Guidance on the verification of quantitative measurement procedures used in the clinical chemistry",the precision,trueness,and linear interval of MAGLUMI 4000 fully automatic chemiluminescence immunoassay analyzer were verified in measuring β-CTx.Results:The intra batch precisions(repeatability)of MAGLUMI 4000 fully automatic chemiluminescence immunoassay analyzer were respectively 3.22%and 3.49%in measuring serum β-CTx samples with low and high values.The intermediate precisions(precision within laboratory)were respectively 4.35%and 3.29%,both of which met the requirements of laboratory.The results of trueness verification showed that the bias of samples with low concentration was-2.4%,and the bias of samples with high concentration was-2.1%.The expected values of the standards with low and high values were all between the corresponding up and low validation limits of them,which met the judgment criteria.The linear interval was 0.03-6.00 ng/mL,which was within the linear interval,and it can meet the requirements of manufacturer′s claim.Conclusion:The precision,trueness and linear interval of MAGLUMI 4000 fully automatic chemiluminescence immunoassay analyzer all passed the verification in measuring β-CTx,which indicates the performance of the project can meet the quality specifications.
7.Clinical study on Chinese materia medica soaking therapy combined with cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy
Di WANG ; Rui XIE ; Lei SHI ; Long GONG ; Jie LUO ; Peiyu SUN
International Journal of Traditional Chinese Medicine 2025;47(12):1682-1686
Objective:To observe the clinical efficacy of Chinese materia medica soaking therapy combined with cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy (CSR).Methods:A randomized controlled trial was conducted. Totally 84 CSR patients from the Orthopedics Department of Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital from April 2023 to May 2024 were selected as the observation subjects. They were divided into two groups using a random number table method, with 42 patients in each group. The treatment for both groups lasted for 14 d. VAS scale was used to assess pain levels before and after treatment, OASTCSR was used to evaluate cervical function, and NDI was used to assess cervical functional status; adverse reactions during treatment were observed and recorded, and clinical efficacy was evaluated.Results:The total effective rate was 95.24% (40/42) in the treatment group and 80.95% (34/42) in the control group, with statistical significance ( χ2=4.36, P=0.029). After treatment, the VAS score (1.60±1.21 vs. 2.91±1.12, t=-1.89), the OASTCSR score (5.17±2.14 vs. 9.31±3.82, t=-11.57), and the NDI score (9.17±2.13 vs. 13.36±3.45, t=-10.82) in the treatment group were lower than those in the control group ( P<0.001 or P<0.05). During the treatment period, neither group experienced any adverse reactions. Conclusion:The combination of Chinese materia medica soaking therapy and cervical rotation-traction manipulation can significantly improve the clinical symptoms and quality of life of patients with CSR, and its efficacy is superior to the use of cervical rotation-traction manipulation alone.
8.A photodynamic nanohybrid system reverses hypoxia and augment anti-primary and metastatic tumor efficacy of immunotherapy.
Haitao YUAN ; Xiaoxian WANG ; Xin SUN ; Di GU ; Jinan GUO ; Wei HUANG ; Jingbo MA ; Chunjin FU ; Da YIN ; Guohua ZENG ; Ying LONG ; Jigang WANG ; Zhijie LI
Acta Pharmaceutica Sinica B 2025;15(6):3243-3258
Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.
9.Guidelines for the Digital Ancient Books of TCM Indexing
Weina ZHANG ; Bing LI ; Bin LI ; Jing XIE ; Yan DONG ; Wei LONG ; Chuchu ZHANG ; Tong WEI ; Sihong LIU ; Yang WU ; Hongtao LI ; Lin TONG ; Guangkun CHEN ; Fei DONG ; Rui WANG ; He LU ; Meng LI ; Jingpeng DENG ; Tengfei WANG ; Xiaoying LI ; Di ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(3):1-11
Guidelines for Digital Ancient Books of TCM Indexing(T/CIATCM 119-2024)is based on the theoretical knowledge,disciplinary methods,and practical applications of TCM classical cataloging.Taking digital ancient books of TCM as the object,it systematically reveals the content of TCM knowledge,which is an essential indexing processing standard for building an intelligent retrieval system for TCM ancient books,and can provide support for the deep development and innovative utilization of TCM knowledge.It can not only promote the co-construction and sharing of ancient book resources in the TCM industry,but also promote the standardization construction and application of TCM information.This standard specifies the principles,methods,and examples of free indexing of digital ancient books of TCM based on their original content.It is applicable to the indexing and processing of digital ancient books of TCM for TCM professional libraries and related institutions,and to the data processing and construction of various types of TCM ancient book databases.
10.The value of DCE-MRI combined with spectral CT in the short-term efficacy of concurrent chemoradiotherapy for nasopharyngeal carcinoma.
Shucheng ZHENG ; Dejiang ZHANG ; Yuan ZHAO ; Di CHEN ; Long WANG ; Libin TANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(9):848-853
Objective:To explore the value of spectral CT parameters combined with dynamic contrast enhanced magnetic resonance imaging(DCE-MRI) parameters in the short-term efficacy of concurrent chemoradiotherapy for nasopharyngeal carcinoma. Methods: A total of 110 cases with nasopharyngeal carcinoma Ⅲ-Ⅳ staging who received synchronous radiotherapy and chemotherapy at our Hospital from October 2022 to October 2024 were regarded as the study subjects. Complying with the evaluation results after radiotherapy and chemotherapy, they were divided into a complete remission(CR) group of 53 cases and a non CR group of 57 cases. All patients underwent DCE-MRI and energy dispersive CT scans to obtain parameters, such as iodine concentration(IC), volume transfer constant(Ktrans), slope of spectral HU curve(λHU), rate constant(Kep), and normalized iodine concentration(NIC). Logistic regression analysis was used to screen for influencing factors. ROC curve was used to analyze the evaluation value of various parameters. In addition, Z-test was used to compare area under the curve(AUC). Results:The proportion of retropharyngeal lymph node metastasis and λHUvalue in the non CR group were higher than those in the CR group, while Ktrans, Kep, IC value, and NIC value were lower than those in the CR group(P<0.05). Retropharyngeal lymph node metastasis, Ktrans, Kep, IC value, λHUvalue, and NIC value were all influencing factors(P<0.05). The AUC of individual prediction of Ktrans, Kep, IC value, λHUvalue, and NIC value was 0.817, 0.800, 0.785, 0.783, and 0.835, respectively. The AUC of the combination of DCE-MRI parameters, the combination of spectral CT parameters, and the combination of the five parameters were 0.874, 0.900, and 0.980, respectively, the AUC of the combination of the five parameters was significantly higher than the AUC of each indicator alone, the AUC of the combination of DCE-MRI parameters, and the AUC of the combination of spectral CT parameters(P<0.05). Conclusion:The DCE-MRI, and spectral CT parameters (Ktrans, Kep, IC value, λHUvalue, and NIC value)can be used to evaluate concurrent radiotherapy and chemotherapy short-term efficacy for nasopharyngeal carcinoma. And the combination of various parameters can greatly improve the predictive value of efficacy, which has important clinical application value.
Humans
;
Chemoradiotherapy
;
Nasopharyngeal Neoplasms/diagnostic imaging*
;
Magnetic Resonance Imaging
;
Nasopharyngeal Carcinoma
;
Tomography, X-Ray Computed
;
Male
;
Female
;
Contrast Media
;
Middle Aged
;
Adult
;
Lymphatic Metastasis
;
Dynamic Contrast Enhanced Magnetic Resonance Imaging

Result Analysis
Print
Save
E-mail