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.

In this study,an ON/OFF type micro-valve with a sandwich(glass-silicon-glass)structure was designed and fabricated based on the micro-electro-mechanical system(MEMS)technique.The deformable membrane of this micro-valve was prepared on the silicon on insulator(SOI)substrate and sealed using Si-Si bonding and anodic bonding methods.The micro-valve had high-temperature stability and was suitable for integration with other gas chromatography components.The deformable membrane with a thickness of 10 μm was processed on the top silicon of the SOI substrate.The flow control of the micro-valve could be achieved by changing the driving pressure applied to the deformable membrane to deform it.Compared with polymer membranes,the deformable membrane prepared on the top layer silicon of SOI had better temperature stability and could be released using the deep reactive ion etching technique after silicon-silicon bonding,avoiding deformation during the preparation process.In addition,due to the small gap between the membrane and the inlet/outlet holes,the dead volume of the microvalve was very small.The test results indicated that the micro-valve achieved flow control and ON/OFF functions with good repeatability.

A monolithic integrated gas chromatography chip,consisting of a micro gas chromatography column(μGCC)and a micro helium discharge ionization detector(μHDID)was proposed.The chip was fabricated using micro electromechanical system(MEMS)technique,and its sensitivity was improved from two aspects.On one hand,open tubular column was selected as the separation device,and the auxiliary helium channel width of μHDID was modulated based on the microchannel width of the μGCC to match the flow rates of μHDID and μGCC.On the other hand,the electrode structure inside the μHDID collection zone was optimized,a bias electrode group around the collection electrode was constructed,and the ion collection efficiency was improved.After coating HKUST-1 as the stationary phase,the monolithic integrated gas chromatography chip could achieve baseline separation and detection of light hydrocarbon gas mixture(methane,ethane,propane,andn-butane),with a detection limit for propane as low as 25 pg.The chip could carried out test under temperature-programmed conditions,with a resolution of 9.24 for ethane and propane.

A micro gas chromatographic column with mesoporous surface micro column array prepared by anodization method was proposed.A porous support layer with a characteristic pore size of about 30 nm inside the chromatographic column was prepared in situ using anodization method,and a uniform alumina stationary phase was deposited on the mesoporous support layer using atom layer deposition(ALD)technique.The existence of a mesoporous support layer increased surface area of the chromatographic column,thereby increasing the total amount of stationary phase loading and enhancing column capacity,which facilitated chromatographic separation.The test results showed that the porous support layer significantly reduced the longitudinal molecular diffusion and mass transfer resistance of the micro gas chromatographic column,and significantly increased the number of theoretical plates(n-nonane increased by 290.2%).Furthermore,column efficiency of the chromatographic column was less affected by flow rate,which was conducive to rapid separation of heavy hydrocarbon mixtures.

Objective:By analyzing the differential miRNA in seminal plasma between individuals with normal and abnormal sperm DNA fragmentation index(DFI),we aim to identify miRNA that may impact sperm DNA integrity and target genes,and attempt to analyze their potential mechanisms of action.Methods:A total of 161 study subjects were collected and divided into normal con-trol group,DFI-medium group and DFI-abnormal group based on the DFI detection values.Differential miRNA were identified through miRNA chip analysis.Through bioinformatics analysis and target gene prediction,miRNA related to DFI and specific target genes were identified.The relative expression levels of differential miRNA and target genes in each group were compared to explore the impact of their differential expression on DFI.Results:Through miRNA chip analysis,a total of 11 differential miRNA were detected.Bioin-formatics analysis suggested that miR-26a-5p may be associated with reduced sperm DNA integrity.And gene prediction indicated that PTEN was a specific target gene of miR-26a-5p.Compared to the normal control group,the relative expression levels of miR-26a-5p in both the DFI-medium group and the DFI-abnormal group showed a decrease,while the relative expression levels of PTEN showed an in-crease.The relative expression levels of miR-26a-5p in all groups were negatively correlated with DFI values,while the relative expres-sion levels of PTEN showed a positive correlation with DFI values in the DFI-medium group and the DFI-abnormal group.The AUC of miR-26a-5p in the DFI-medium group was 0.740(P＜0.05),with a sensitivity of 73.6％and a specificity of 71.5％;the AUC of PTEN was 0.797(P＜0.05),with a sensitivity of 76.5％and a specificity of 78.4％.In the DFI-abnormal group,the AUC of miR-26a-5p was 0.848(P＜0.05),with a sensitivity of 81.3％and a specificity of 78.1％.While the AUC of PTEN was 0.763(P＜0.05),with a sensitivity of 77.2％and a specificity of 80.2％.Conclusion:miR-26a-5p affects the integrity of sperm DNA by regulating the expression of PTEN negatively.The relative expression levels of seminal plasma miR-26a-5p and PTEN have good diag-nostic value for sperm DNA integrity damage,which can help in the etiological diagnosis and prognosis analysis of abnormal DFI.This provides a diagnostic and treatment approach for the study and diagnosis of DFI abnormalities without clear etiology.

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective To investigate the effects of peripheral blood neutrophil infiltration on the polarization regulation of cerebral resident microglia under a permanent ischemic stroke model.Methods Fifty-eight C57BL/6 mice were divided into two groups.One group was sham group,and the other group of mice was subjected to permanent middle cerebral artery occlusion surgery.Mice were euthanized 48 hours,7 days,14 days,and 30 days after surgery for tissue collection.Western blotting was used to detect expression levels of M1 microglia markers CD 16,M2 microglia marker arginase 1(Arg1),inflammatory cytokine interleukin-1 β(IL-1β),and neutrophil marker myeloperoxidase(MPO)in brain tissue.Immunofluorescence histochemical staining was used to assess neutrophil infiltration and M2 microglial distribution around the infarct area in brain sections.In vitro,purified neutrophils were co-cultured with BV2 microglial cells.After lipopolysaccharide stimulation,the phagocytosis of neutrophils by BV2 cells was observed,and the expression levels of CD16 and Arg1 proteins in BV2 cells were detected.Results Western blotting showed that the levels of CD16(P＜0.05),IL-1β(P＜0.001),and MPO(P＜0.05)in brain tissue increased significantly 48 hours and 7 days after surgery,then decreased,with MPO expression returning to normal levels 30 days after surgery.Immunofluorescence showed a significant increase of MPO-positive cells around the infarct area of the mouse cerebral cortex 48 hours after surgery(P＜0.001),followed by a decrease(P＜0.05).The number of ionized calcium binding adapter molecule 1(Iba1)and MPO double-positive cells gradually increased after surgery,and reached their peak at 14 days(P＜0.05).Iba1 and Arg1 double-positive cells also increased significantly 7 days(P＜0.05)and 14 days(P＜0.01)after surgery.In vitro,co-culture experiments showed that after BV2 phagocytosing neutrophils,CD 16(P＜0.05)significantly decreased and Arg1 significantly upregulated(P＜0.05).Conclusion In a permanent ischemic stroke model,microglia transition from M1 to M2 type after phagocytosing neutrophils,and the injured brain area changes from pro-inflammatory state to anti-inflammatory state.

The purpose of this study was to clarify the effect of Huotan Jiedu Tongluo Decoction on atherosclerosis(AS) injury in ApoE~(-/-) mice by regulating the ferroptosis pathway. Seventy-five ApoE~(-/-) mice were randomly divided into model group, low-, medium-, and high-dose of Huotan Jiedu Tongluo Decoction groups, and evolocumab group(n=15), and 15 C57BL/6J mice were selected as the blank group. Mice in the blank group were fed with a normal diet, and those in the other groups were fed with a high-fat diet to induce AS. From the 9th week, mice in Huotan Jiedu Tongluo Decoction groups were administrated with Huotan Jiedu Tongluo Decoction at corresponding doses by gavage, and those in the blank group and the model group were given an equal volume of distilled water. Mice in the evolocumab group were treated with evolocumab 18.2 mg·kg~(-1 )by subcutaneous injection every 2 weeks. After 8 weeks of continuous intervention, oil red O staining and hematoxylin-eosin(HE) staining were employed to observe the lipid deposition and plaque formation in the aortic root. Masson staining was used to evaluate the collagen content in the aortic root. The serum levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were determined by biochemical kits. The levels of Fe~(2+), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the aorta were measured by colorimetry. The protein and mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), and acyl-CoA synthetase long chain family member 4(ACSL4) in the aorta were detected by Western blot and RT-qPCR, respectively. The expression of Nrf2, GPX4, and SLC7A11 was localized by immunofluorescence. The results showed that low-, medium-, and high-dose Huotan Jiedu Tongluo Decoction reduced the plaque formation of aortic root and increased the collagen content in AS mice. At the same time, Huotan Jiedu Tongluo Decoction improved the lipid metabolism by lowering the levels of TC, LDL-C, and TG and elevating the level of HDL-C in the serum. Huotan Jiedu Tongluo Decoction enhanced the antioxidant capacity by elevating the levels of GSH and SOD and lowering the level of MDA in the aorta and inhibiting the accumulation of Fe~(2+) in the aorta. In addition, Huotan Jiedu Tongluo Decoction up-regulated the protein and mRNA levels of Nrf2, GPX4, and SLC7A11, while down-regulating the protein and mRNA levels of ACSL4. In summary, Huotan Jiedu Tongluo Decoction can effectively alleviate AS lesions in ApoE~(-/-) mice by activating the Nrf2/GPX4 pathway, reducing lipid peroxidation, and inhibiting ferroptosis.
Animals ; Ferroptosis/drug effects* ; Atherosclerosis/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/genetics* ; Mice ; Mice, Inbred C57BL ; Apolipoproteins E/metabolism* ; Male ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Signal Transduction/drug effects* ; Humans ; Mice, Knockout