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.

This article presents a comprehensive review of new methods for target identification of complex components in tradi-tional Chinese medicine(TCM)and research progress in their applications.It systematically summarizes classical approaches and cutting-edge technical systems for target identification,cov-ering multiple strategies such as proteomic analysis,fluorescence resonance energy transfer(FRET)technology,network pharma-cology prediction models,high-throughput biochip screening,tar-get capture strategies based on molecular affinity fishing,gene site-directed mutagenesis verification,and co-crystallization structure analysis of target proteins.The review emphasizes the critical role of target identification in elucidating the action mechanisms of TCM and facilitating new drug development,lay-ing a foundation for promoting the modernization of TCM.

OBJECTIVE To offer a reference for the treatment of Mycobacterium iranicum infection by analyzing the diagnosis and management of a single case alongside literature-reported cases.METHODS Through case report and literature reviews,this study synthesized the clinical features,therapeutic regimens,and patient outcomes of those infected with M.iranicum.RESULTS In the single case documented in this report,subsequent to clinical pharmacists'involvement in the consultation,the patient was prescribed a therapeutic regimen comprising levofloxacin(0.5 g,qd,ivgtt)+Clarithromycin sustained-release tablets(1 000 mg,qd,po)+Ethambutol tablets(0.75 g,qd,po).The patient exhibited clinical improvement and was discharged after treatment.This article integrated 12 published studies,encompassing 13 patients(7 male and 6 female),of whom 69.23%were aged≥50 years.Patients infected with M.iranicum exhibited non-specific clinical manifestations and imaging features,with pulmonary infection as the primary presentation.Antimicrobial susceptibility test revealed that M.iranicum was susceptible to multiple agents,including amikacin,clarithromycin,linezolid,and ethambutol.The three-drug combination therapy was the most frequently employed regimen.In terms of clinical outcomes,there were 9 cases(69.23%)of clinical cure,3 cases(23.08%)of bacteriological negativity conversion,and 1 case(7.69%)of treatment failure.CONCLUSIONS For M.iranicum infection,a triple-drug therapeutic regimen consisting of three agents with distinct mechanisms of action selected from amikacin,clarithromycin,moxifloxacin,levofloxacin,minocycline,ethambutol,and other relevant drugs may represent a relatively optimal strategy.

Objective To explore the mechanism by which the triggering receptor expressed on Myeloid cells-like 4(TREML4)regulates nuclear factor-kappaB(NF-κB)pathway mediates neutrophil extracellular traps(NETs)aggravating rheumatoid arthritis(RA).Methods RA model was induced by subcutaneous injection of Freund adjuvant and bovine collagen type Ⅱ in DBA/1J mice.We used phorbol 12-myristate 13-acetate(PMA)to induce neutrophils to form NETs.We observed the degree of joint swelling and other morphological indicators,used hematoxylin-eosin staining(HE)staining to observe the pathology of the ankle joint,used enzyme-linked immunosorbent assay(ELISA)to measure the levels of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum,used western blot to detect the expression of myeloperoxidase(MPO)and citrullinated histone H3(CitH3)for assess the release of NETs in the ankle joint of mice,used western blot to detect the expression of TREML4 and NF-κB pathway-associated proteins nuclear factor kappa B inhibitor α(IκBα)and NF-κB p65,used immunofluorescence to detect the distribution of MPO and CitH3 in neutrophils to assess the formation of NETs.Results Compared with the control group,the RA group exhibited joint swelling,bone erosion,excessive infiltration of immune cells and cartilage damage,and the serum inflammatory fac-tors IL-6,TNF-α and IL-1β were significantly increased(P＜0.01),the expression of IκBα was significantly decreased(P＜0.01),and the expression of NF-κB p65 was significantly increased(P＜0.01).Compared with control group,the number of NETs formed by neutrophils in PMA group was significantly increased,the expression of TREML4 and NF-κB p65 was significantly increased(P＜0.01),and the expression of IκBα was significantly decreased(P＜0.01).Compared with the PMA+si-NC group,the number of NETs formed by neutrophils in the PMA+si-TREML4group was significantly reduced(P＜0.01),the expression of TREML4 and NF-κB p65 was significantly decreased(P＜0.01),and the expression of IκBα was significantly increased(P＜0.01).Conclusion TREML4 can regulate the formation of NETs mediated by NF-κB pathway to aggravate RA.

This article presents a comprehensive review of new methods for target identification of complex components in tradi-tional Chinese medicine(TCM)and research progress in their applications.It systematically summarizes classical approaches and cutting-edge technical systems for target identification,cov-ering multiple strategies such as proteomic analysis,fluorescence resonance energy transfer(FRET)technology,network pharma-cology prediction models,high-throughput biochip screening,tar-get capture strategies based on molecular affinity fishing,gene site-directed mutagenesis verification,and co-crystallization structure analysis of target proteins.The review emphasizes the critical role of target identification in elucidating the action mechanisms of TCM and facilitating new drug development,lay-ing a foundation for promoting the modernization of TCM.

Objective To systematically evaluate the effect of inspiratory muscle training(IMT)on weaning outcomes in patients with weaning failure.Methods Literatures in Chinese and English were retrieved from databases such as PubMed,Cochrane Library,Web of Science,Embase,CNKI,VIP,Wanfang data and CBM for researches on the effect of IMT in mechanical ventila-tion weaning failure,from the inception of the databases to October 22,2024.The methodological quality of the researches was evaluated with PEDro scale,and data were extracted for a systematic review.Results Nine randomized controlled trials were included,published between 2011 and 2023,from Brazil,China,the United States,Iran and Australia,with a total of 499 patients.The scores of the PEDro scale ranged five to eight.The population included patients with prolonged weaning,difficult weaning and tracheostomy.The IMT methods included threshold load training and tapered flow resistance training.The training intensity was 30%to 80%of maximal inspiratory pressure(MIP),and some researches did not set the training intensity based on MIP.The pro-gression of intensity varied widely across researches.The intervention frequency ranged from five to 30 breaths per set,with at least one minute rest between sets,two to six sets per session,one to two sessions per day,and five to seven days per week.The duration of the intervention ranged from successful weaning,one week after weaning,extubation,or four days to eight weeks.Regarding the efficacy of the intervention,IMT was not benefi-cial for the duration of mechanical ventilation and intensive care unit(ICU)length of stay on weaning failure pa-tients.However,the effect of IMT on weaning successful rates,duration of weaning,MIP and mortality was in-consistent.Conclusion IMT can not improve the duration of mechanical ventilation and ICU length of stay for weaning failure pa-tients,and there is still debate regarding its effect on successful rate of weaning,duration of weaning,MIP and mortality.

Objective To systematically evaluate the effect of inspiratory muscle training(IMT)on weaning outcomes in patients with weaning failure.Methods Literatures in Chinese and English were retrieved from databases such as PubMed,Cochrane Library,Web of Science,Embase,CNKI,VIP,Wanfang data and CBM for researches on the effect of IMT in mechanical ventila-tion weaning failure,from the inception of the databases to October 22,2024.The methodological quality of the researches was evaluated with PEDro scale,and data were extracted for a systematic review.Results Nine randomized controlled trials were included,published between 2011 and 2023,from Brazil,China,the United States,Iran and Australia,with a total of 499 patients.The scores of the PEDro scale ranged five to eight.The population included patients with prolonged weaning,difficult weaning and tracheostomy.The IMT methods included threshold load training and tapered flow resistance training.The training intensity was 30%to 80%of maximal inspiratory pressure(MIP),and some researches did not set the training intensity based on MIP.The pro-gression of intensity varied widely across researches.The intervention frequency ranged from five to 30 breaths per set,with at least one minute rest between sets,two to six sets per session,one to two sessions per day,and five to seven days per week.The duration of the intervention ranged from successful weaning,one week after weaning,extubation,or four days to eight weeks.Regarding the efficacy of the intervention,IMT was not benefi-cial for the duration of mechanical ventilation and intensive care unit(ICU)length of stay on weaning failure pa-tients.However,the effect of IMT on weaning successful rates,duration of weaning,MIP and mortality was in-consistent.Conclusion IMT can not improve the duration of mechanical ventilation and ICU length of stay for weaning failure pa-tients,and there is still debate regarding its effect on successful rate of weaning,duration of weaning,MIP and mortality.

Objective To explore the mechanism by which the triggering receptor expressed on Myeloid cells-like 4(TREML4)regulates nuclear factor-kappaB(NF-κB)pathway mediates neutrophil extracellular traps(NETs)aggravating rheumatoid arthritis(RA).Methods RA model was induced by subcutaneous injection of Freund adjuvant and bovine collagen type Ⅱ in DBA/1J mice.We used phorbol 12-myristate 13-acetate(PMA)to induce neutrophils to form NETs.We observed the degree of joint swelling and other morphological indicators,used hematoxylin-eosin staining(HE)staining to observe the pathology of the ankle joint,used enzyme-linked immunosorbent assay(ELISA)to measure the levels of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum,used western blot to detect the expression of myeloperoxidase(MPO)and citrullinated histone H3(CitH3)for assess the release of NETs in the ankle joint of mice,used western blot to detect the expression of TREML4 and NF-κB pathway-associated proteins nuclear factor kappa B inhibitor α(IκBα)and NF-κB p65,used immunofluorescence to detect the distribution of MPO and CitH3 in neutrophils to assess the formation of NETs.Results Compared with the control group,the RA group exhibited joint swelling,bone erosion,excessive infiltration of immune cells and cartilage damage,and the serum inflammatory fac-tors IL-6,TNF-α and IL-1β were significantly increased(P＜0.01),the expression of IκBα was significantly decreased(P＜0.01),and the expression of NF-κB p65 was significantly increased(P＜0.01).Compared with control group,the number of NETs formed by neutrophils in PMA group was significantly increased,the expression of TREML4 and NF-κB p65 was significantly increased(P＜0.01),and the expression of IκBα was significantly decreased(P＜0.01).Compared with the PMA+si-NC group,the number of NETs formed by neutrophils in the PMA+si-TREML4group was significantly reduced(P＜0.01),the expression of TREML4 and NF-κB p65 was significantly decreased(P＜0.01),and the expression of IκBα was significantly increased(P＜0.01).Conclusion TREML4 can regulate the formation of NETs mediated by NF-κB pathway to aggravate RA.

Objective To explore the correlation between osteocalcin (OCN) and visceral fat area (VFA) in overweight/obese population. Methods The data of 297 overweight/obese people who underwent health examinations in Health Management Department of Second Affiliated Hospital of Xi'an Jiaotong University from August 2021 to August 2024 were analyzed. According to the VFA value measured by InBody, the subjects were divided into an excessive group (VFA ≥100 cm²) and a normal group (VFA<100 cm2). The baseline data, glucose metabolism indicators, lipid metabolism indicators and OCN were compared between the two groups. Binary logistic regression analysis was used to analyze the independent risk factors affecting visceral fat deposition in overweight/obese people. Results According to the VFA value, there were 193 cases (64.98%) in the excessive group and 104 cases (35.02%) in the normal group. There were no statistical differences in gender, age and comorbidities between the two groups (P>0.05). The BMI, FPG, HbA1c, TC, TG, and LDL-C in the excessive group were higher than those in the normal group, while the HDL-C and OCN were lower than those in the normal group (P<0.05). Binary logistic regression analysis revealed that BMI, FPG, HbA1c, TC, TG and LDL-C were independent risk factors for visceral fat deposition in overweight/obese people, while HDL-C and OCN were protective factors (P<0.05). Conclusion Visceral fat deposition in overweight/obese people is closely related to OCN content, and is affected by abnormal glucolipid metabolism, which provides new ideas for the prevention and treatment of obesity-related diseases.