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 explore the factors influencing the blood concentration of voriconazole in elderly hospitalized patients and inform the probability of attaining the target concentration in clinical practice.Methods Patients aged ≥65 years who were hospitalized in the First Affiliated Hospital of Anhui Medical University from January 2022 to December 2023 and underwent voriconazole blood concentration monitoring were enrolled.Their voriconazole blood concentrations and clinical data were collected.The patients were grouped according to the target effective concentration 0.5-5.0 mg/L of voriconazole recommended by the Chinese Pharmacological Society guidelines.Multivariate logistic regression analysis was used to determine the factors affecting the rate of achieving the target concentration.Results The 202 enrolled patients included 139 males and 63 females.A total of 244 voriconazole blood concentrations were available.The median age of the patients was 74(range:65-95)years.Voriconazole blood concentration ranged from 0.08 to 13.38 mg/L.The average concentration was(4.10±2.45)mg/L.The target effective blood concentration of voriconazole was achieved in 65.35％(132/202)of the patients.Logistic regression results showed that the dosage regimen,body weight,and hypoproteinemia(albumin＜25 g/L)were the main factors affecting voriconazole blood concentration.Conclusions The dosing regimen,body weight,and hypoproteinemia are the main influencing factors of voriconazole blood concentration.Relevant factors should be fully considered in clinical medication to ensure the safety and effectiveness of voriconazole.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Objective:To evaluate the impact of Diagnosis-Intervention Packet(DIP)payment reform on medical service costs and efficiency for inpatients in public hospitals,and to compare differences between surgical and medical groups.Methods:A quasi-experimental design was employed,using 605 636 discharged patients from a tertiary hospital in Hebei Province between January 2020 and March 2025 as the sample.The difference-in-differences(DID)model was used to analyze the changes in key indicators between the DIP settlement group(intervention group)and the non-DIP settlement group(control group).Results:Total hospitalization costs,out-of-pocket expenses,and medication costs were significantly reduced in the DIP settlement group(P<0.05),while costs for examinations,nursing,laboratory tests,and treatments increased significantly(P<0.05).Material costs increased by 30.7%in the surgical group(P<0.1)and decreased by 19.8%in the medical group(P<0.01).In terms of efficiency,the average length of stay,time,and cost consumption index all decreased(P<0.01),while the proportion of medical services increased(P<0.01).The case mix index(CMI)showed no significant changes.Conclusion:The DIP reform effectively controlled costs and improved efficiency,but it also resulted in cost shifting and departmental disparities.Therefore,it is necessary to optimize cost control and departmental management policies.

Objective Exploring the diagnostic value of T-cell enzyme-linked immunospot assay(T-SPOT.TB)combined with rifampicin-resistant Mycobacterium tuberculosis real-time fluorescence quantitative nucleic acid ampli-fication detection(XpertMTB/RIF)in geriatric AIDS patients with Mycobacterium tuberculosis(MTB)infection.Methods From May 2022 to May 2024,86 elderly patients with AIDS suspected MTB in Hengshui Third People's Hospital were gathered and separated into AIDS complicated with MTB(research group)and AIDS without MTB(control group)according to the pathological examination results.MTB culture,T-SPOT.TB and XpertMTB/RIF were performed.Kappa analysis was applied to evaluate the consistency between T-SPOT.TB combined with Xpert-MTB/RIF and the gold standard for diagnosing MTB coinfection in AIDS patients.ROC curve and four grid table were plotted to analyze the value of the combination of T-SPOT.TB and XpertMTB/RIF in the diagnosis of AIDS complicated with MTB infection.Results The blood γ-interferon,the positive detection rates of T-SPOT.TB and XpertMTB/RIF in the research group were higher than those in the control group(P＜0.05).The AUC of T-SPOT.TB in diagnosing AIDS with MTB infection was 0.810,that of Xpert MTB/RIF in diagnosing AIDS with MTB infection was 0.835,and the AUC of the two in diagnosing AIDS with MTB infection was 0.910.The Kappa values of T-SPOT.TB,Xpert MTB/RIF and their combined diagnosis for AIDS with MTB infection were 0.624,0.674 and 0.825,respectively.The accuracy of T-SPOT.TB in the diagnosis of AIDS with MTB was 82.56%,the accuracy of XpertMTB/RIF in the diagnosis of AIDS with MTB was 84.88%,and the accuracy of the combined di-agnosis for AIDS with MTB was 91.86%.Conclusions T-SPOT.TB combined with XpertMTB/RIF can improve the accuracy of diagnosis of AIDS with MTB,and can be used as a clinical auxiliary diagnosis method for AIDS pa-tients complicated with MTB.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Objective To explore the factors influencing the blood concentration of voriconazole in elderly hospitalized patients and inform the probability of attaining the target concentration in clinical practice.Methods Patients aged ≥65 years who were hospitalized in the First Affiliated Hospital of Anhui Medical University from January 2022 to December 2023 and underwent voriconazole blood concentration monitoring were enrolled.Their voriconazole blood concentrations and clinical data were collected.The patients were grouped according to the target effective concentration 0.5-5.0 mg/L of voriconazole recommended by the Chinese Pharmacological Society guidelines.Multivariate logistic regression analysis was used to determine the factors affecting the rate of achieving the target concentration.Results The 202 enrolled patients included 139 males and 63 females.A total of 244 voriconazole blood concentrations were available.The median age of the patients was 74(range:65-95)years.Voriconazole blood concentration ranged from 0.08 to 13.38 mg/L.The average concentration was(4.10±2.45)mg/L.The target effective blood concentration of voriconazole was achieved in 65.35％(132/202)of the patients.Logistic regression results showed that the dosage regimen,body weight,and hypoproteinemia(albumin＜25 g/L)were the main factors affecting voriconazole blood concentration.Conclusions The dosing regimen,body weight,and hypoproteinemia are the main influencing factors of voriconazole blood concentration.Relevant factors should be fully considered in clinical medication to ensure the safety and effectiveness of voriconazole.

Objective:To evaluate the impact of Diagnosis-Intervention Packet(DIP)payment reform on medical service costs and efficiency for inpatients in public hospitals,and to compare differences between surgical and medical groups.Methods:A quasi-experimental design was employed,using 605 636 discharged patients from a tertiary hospital in Hebei Province between January 2020 and March 2025 as the sample.The difference-in-differences(DID)model was used to analyze the changes in key indicators between the DIP settlement group(intervention group)and the non-DIP settlement group(control group).Results:Total hospitalization costs,out-of-pocket expenses,and medication costs were significantly reduced in the DIP settlement group(P<0.05),while costs for examinations,nursing,laboratory tests,and treatments increased significantly(P<0.05).Material costs increased by 30.7%in the surgical group(P<0.1)and decreased by 19.8%in the medical group(P<0.01).In terms of efficiency,the average length of stay,time,and cost consumption index all decreased(P<0.01),while the proportion of medical services increased(P<0.01).The case mix index(CMI)showed no significant changes.Conclusion:The DIP reform effectively controlled costs and improved efficiency,but it also resulted in cost shifting and departmental disparities.Therefore,it is necessary to optimize cost control and departmental management policies.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.