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.

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.

Objective:To analyze the evolution and diffusion characteristics of policies related to life expectancy(LE)and healthy life expectancy(HLE)in China from 1982 to 2024 using a biometric approach to policy analysis,revealing the patterns of policy diffusion.Methods:By retrieving databases such as PKULAW.com,We comprehensively collected 701 policy documents closely related to LE and HLE during the period(including 62 central policies and 639 local policies),the policy diffusion process was quantified in four dimensions:diffusion intensity,diffusion breadth,diffusion speed and diffusion direction by using the policy—reference network analysis method.Results:Related policy has gone through the germination period(1982-2001),the development period(2002-2010),the rapid rise period(2011-2015)and the four stages of innovation and pioneering period(2016—present).Policy diffusion is influenced by the hierarchical level of the issuing institution,policy type,and regional economic development level.Policies promulgated by central institutions exhibit stronger and broader diffusion,with guideline—type policies diffusing most widely.The diffusion rate follows a trend of"initial growth,followed by deceleration,and then a slight increase."The primary diffusion directions are vertical diffusion from central to local levels and horizontal diffusion among peers.Conclusion:The diffusion of policies related to LE and HLE is characterized by significant stages,regions and levels.

Objective:To compare the characteristics and temperature changes of single and double fiber Nd∶YAG laser in fresh isolated pig liver,and to provide reference for clinical ablation treatment.Methods:Single-needle single-point and double-needle double-point ablations were perf ormed on fresh isolated pig livers using a 5 W power laser,and the morphology,range,and surrounding temperature changes of the ablation lesions caused by the two in vitro liver tissues were observed.Results:The ablation lesions were divided into carbonized area,necrotic area and deformed area from inside to outside.The carbonized area in the center of the ablation lesion in the double-fiber group was larger and the cell necrosis was more thorough.The aspect ratio(LD/TD)of the laser ablation lesion in the single-fiber group was larger than that in the double fiber group(P＜0.001).The transverse diameter(TD)and volume(V)of the ablation lesion in the double-fiber group were larger than those in the single-fiber group(P＜0.001).There was no significant difference in the longitudinal diameter(LD)of the ablation lesion between the double-fiber group and the single-fiber group(P＞0.05).There was no significant difference in the temperature of 20 s,40 s and 60 s at 5 mm and 10 mm beside the ablation center between the two groups(all P＞0.05).Conclusion:Under the condition of 5 W,the temperature changes around the single and double fiber ablation are similar.The single fiber is suitable for small tumor ablation,and the double fiber ablation range is larger,which can be used for one-time full coverage ablation of larger cancer nodules.

Objective:To compare the characteristics and temperature changes of single and double fiber Nd∶YAG laser in fresh isolated pig liver,and to provide reference for clinical ablation treatment.Methods:Single-needle single-point and double-needle double-point ablations were perf ormed on fresh isolated pig livers using a 5 W power laser,and the morphology,range,and surrounding temperature changes of the ablation lesions caused by the two in vitro liver tissues were observed.Results:The ablation lesions were divided into carbonized area,necrotic area and deformed area from inside to outside.The carbonized area in the center of the ablation lesion in the double-fiber group was larger and the cell necrosis was more thorough.The aspect ratio(LD/TD)of the laser ablation lesion in the single-fiber group was larger than that in the double fiber group(P＜0.001).The transverse diameter(TD)and volume(V)of the ablation lesion in the double-fiber group were larger than those in the single-fiber group(P＜0.001).There was no significant difference in the longitudinal diameter(LD)of the ablation lesion between the double-fiber group and the single-fiber group(P＞0.05).There was no significant difference in the temperature of 20 s,40 s and 60 s at 5 mm and 10 mm beside the ablation center between the two groups(all P＞0.05).Conclusion:Under the condition of 5 W,the temperature changes around the single and double fiber ablation are similar.The single fiber is suitable for small tumor ablation,and the double fiber ablation range is larger,which can be used for one-time full coverage ablation of larger cancer nodules.

Objective:To analyze the evolution and diffusion characteristics of policies related to life expectancy(LE)and healthy life expectancy(HLE)in China from 1982 to 2024 using a biometric approach to policy analysis,revealing the patterns of policy diffusion.Methods:By retrieving databases such as PKULAW.com,We comprehensively collected 701 policy documents closely related to LE and HLE during the period(including 62 central policies and 639 local policies),the policy diffusion process was quantified in four dimensions:diffusion intensity,diffusion breadth,diffusion speed and diffusion direction by using the policy—reference network analysis method.Results:Related policy has gone through the germination period(1982-2001),the development period(2002-2010),the rapid rise period(2011-2015)and the four stages of innovation and pioneering period(2016—present).Policy diffusion is influenced by the hierarchical level of the issuing institution,policy type,and regional economic development level.Policies promulgated by central institutions exhibit stronger and broader diffusion,with guideline—type policies diffusing most widely.The diffusion rate follows a trend of"initial growth,followed by deceleration,and then a slight increase."The primary diffusion directions are vertical diffusion from central to local levels and horizontal diffusion among peers.Conclusion:The diffusion of policies related to LE and HLE is characterized by significant stages,regions and levels.

This study aims to observe the effects of different doses of Astragali Radix on the expression of glucagon(GLP-1) in se-rum and glucagon receptor(GLP-1R) in cartilage tissue in rats with knee osteoarthritis(KOA), explore the effect of Astragali Radix on the inflammation and apoptosis of KOA by regulating GLP-1/GLP-1R signaling axis, and investigate the mechanism of its action in alleviating KOA. Forty-eight male SD rats were randomly divided into six groups: blank group, model group, low-, medium-, and high-dose Astragali Radix groups(3.125, 6.25, and 12.5 g·kg~(-1)), and glucosamine sulfate group(0.1 g·kg~(-1)). Except for the blank group, rats in other groups were injected with sodium iodoacetate(MIA) into the knee joint to establish KOA models. After successful modeling, the rats were continuously treated for five weeks. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of GLP-1, tumor necrosis factor-alpha(TNF-α), and interleukin-1β(IL-1β) in rat serum. Pathological examination was utilized to observe the pathological changes in knee joint cartilage. The mRNA levels of TNF-α and MMP13 in knee joint cartilage were detected by qRT-PCR, and the protein expression levels of GLP-1R, MMP13, and caspase-8 in knee joint cartilage were detected by Western blot. The expression of GLP-1R and MMP13 in the knee joint was detected by immunohistochemistry. Tunel staining was used to observe the apoptosis of chondrocytes in the knee joint. The above experimental results showed that Astragali Radix may raise the serum levels of GLP-1, reduce serum levels of TNF-α and IL-1, and decrease the relative mRNA expression of TNF-α and MMP13 through the GLP-1/GLP-1R axis. It thus activated GLP-1R, reduced the protein expression of MMP13 and caspase-8 in cartilage, and regulated their related signaling pathways to improve inflammation and apoptosis, so as to protect cartilage and improve KOA.
Animals ; Male ; Rats, Sprague-Dawley ; Osteoarthritis, Knee/genetics* ; Rats ; Drugs, Chinese Herbal/pharmacology* ; Glucagon-Like Peptide 1/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Astragalus propinquus/chemistry* ; Humans ; Matrix Metalloproteinase 13/metabolism* ; Signal Transduction/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Astragalus Plant/chemistry* ; Apoptosis/drug effects*

Sonodynamic therapy(SDT)is an emerging approach of cancer treatment that stimulates sonosensitizers by ultrasound to produce reactive oxygen species(ROS)and induce cancer cell death.Compared with organic sonosensitizers,inorganic sonosensitizers have many advantages in stability,toxicity,water solubility,tumor targeting and functional regulation,showing extensive potentials in diagnosis and treatment of tumors.Thanks to the excellent properties,numerous sonosensitizers based on inorganic nanomaterials have been reported,mainly including titanium-based sonosensitizers,other metal-based sonosensitizers and non-metal-based sonosensitizers,and their prospects in diagnosis and treatment of tumor have been discussed.This review introduced the mechanism of SDT,overviewed the research progress of different systems of inorganic sonosensitizers in treatment and diagnosis of tumor,and summarized the methods to improve the therapeutic effect of SDT.Finally,the existing problems and development perspective of inorganic sonosensitizers were discussed and prospected.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.