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 association between the relative expression level of SNORD55 in peripheral blood and the outcomes of all-cause mortality and stroke in patients with atrial fibrillation(AF),and to evaluate the predictive value of SNORD55 for prognosis.Methods A total of 133 patients with non-valvular AF admitted in Department of Cardiology of the First Affiliated Hospital of Army Medical University from January 2014 to December 2017 were enrolled in this study.Their baseline information was collected,and the relative expression level of plasma SNORD55 was detected.Cox proportional hazards model was used to explore the association between the relative expression level of SNORD55 in peripheral blood and all-cause mortality as well as stroke in the patients.The predictive performance of CHA2DS2-VASc score for all-cause mortality and stroke was compared with the score combined with the relative expression level of SNORD55 in the AF patients.The area under the receiver operating characteristic curve(AUC)was utilized to evaluate the discrimination,and the net reclassification index(NRI)and comprehensive discriminant improvement index(IDI)were calculated to evaluate the improvement of reclassification ability.Decision curve analysis(DCA)was applied to analyze the change in clinical net benefit.Results The results of multivariate Cox regression showed that high expression of SNORD55 in peripheral blood was an independent risk factor for all-cause mortality and stroke in the AF patients.In predicting the outcomes of all-cause mortality and stroke,the addition of relative expression SNORD55 level with the CHA2DS2-VASc score obtained higher AUC value[0.80(95％CI:0.67～0.93)vs 0.67(95％CI:0.53～0.81),P＜0.05].In predicting the outcome of all-cause death and stroke,combination of the relative expression level of SNORD55 with CHA2DS2-VASc score increased both NRI[54.3(95％CI:10.6～61.9)vs 31.9(95％CI:2.8～47.5),P＜0.05]and IDI[16.1(95％CI:2.4～27.0)vs 7.9(95％CI:0.5～14.8),P＜0.05].The results of DCA showed that our combination of CHA2DS2-VASc score relative expression level of SNORD55 had higher clinical net benefits than the foreign ABC score in the prediction of the outcomes.Conclusion Peripheral blood SNORD55 level is an independent risk factor for all-cause mortality and stroke in AF patients,and has good predictive performance for all-cause mortality and stroke in the patients.

Objectives To explore the association of peripheral blood PIWI-interacting RNA,piR-hsa-2700592,with all-cause mortality and stroke outcomes in patients with atrial fibrillation(AF),and to determine whether piR-hsa-2700592 has the potential to be an AF biomarker.Methods A total of 127 patients with non-valvular AF were enrolled,and the relative expression level of plasma piR-hsa-2700592 was detected.Cox proportional hazard regression was used to analyze the correlation between the expression of piR-hsa-2700592 and all-cause death as well as stroke outcome in the patients.Then the molecule expression level was combined with CHA2DS2-VASc score and ABC stroke(or death)score to establish 2 new prediction models,the improvement of the predictive performance was compared and analyzed.Receiver operating characteristic(ROC)curve analysis(area under the curve,AUC),net reclassification index(NRI),and comprehensive discriminant improvement index(IDI)were used to evaluate the predictive performance,and decision curve analysis(DCA)was employed to assess the clinical benefit.Results Multivariate Cox regression analysis showed that the patients with higher expression level of piR-hsa-2700592 in peripheral blood had a higher risk of stroke(HR:2.203,95%CI:1.120～4.332;P=0.022).In the stroke outcome,combination of plasma piR-hsa-2700592 expression level with CHA2DS2-VASc score and ABC stroke score obtained an AUC of 0.70(95%CI:0.55～0.85,P＜0.001)and 0.84(95%CI:0.73～0.96,P=0.02),respectively.But,no significant association was observed between high plasma piR-hsa-2700592 level and all-cause mortality in the AF patients(HR:1.997;95%CI:0.884～4.509;P=0.096).Combination of plasma piR-hsa-2700592 level improved the discriminative capability than the single CHA2DS2-VASc score and ABC stroke score models,with an NRI and IDI value of 44.20%(95%CI:3.40～59.90,P＜0.001)and 8.20%(95%CI:0.60～15.40,P＜0.001),respectively for the new CHA2DS2-VASc score model,and an NRI and IDI value of 44.20%(95%CI:9.80～58.90,P＜0.001)and 10.40%(95%CI:0.70～21.40,P＜0.001),respectively for the new ABC stroke score model.The DCA curve showed that both new prediction models obtained better net clinical benefits.Conclusion High peripheral blood expression of piR-hsa-2700592 is an independent risk factor for stroke in the AF patients,and the indicator has a good predictive value for prognosis of the patients.piR-hsa-2700592 might be used as a potential biomarker in the diagnosis and prevention of cardiovascular diseases.

Organophosphorus nerve agents are the most threatening chemical warfare agents and terrorist agents.The number of nerve agents and their related chemicals involved in the verification of Chemical Weapon Convention(CWC)exceeds ten million,with the majority being isomers.Accurate structural identification of these chemicals has always been one of the challenges in CWC related verification analysis.In this work,a total of 17 kinds of alkyl phosphonate isomers and structural analogs from 5 groups were designed and synthesized,and then analyzed by gas chromatography-mass spectrometry(GC-MS)and gas chromatography-infrared spectroscopy(GC-FTIR).The spectra of isomers or structural analogs obtained from two techniques as well as the structural information provided therein were compared and analyzed.The results showed that for isomers or structural analogs with similar MS spectra,FTIR spectra could provided more structural fingerprint information of compounds and had advantages in confirming structures.Combined with the excellent separation ability of GC,GC-FTIR can be used to assist GC-MS in the structural confirmation of alkyl phosphates,achieving rapid and accurate identification of isomers or structural analogues.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

Non-small cell lung cancer(NSCLC) is the most common type of lung cancer worldwide, accounting for approximately 80%-85% of all lung cancer cases. Despite the clinical benefits of traditional treatments such as surgery, chemotherapy, and radiotherapy, challenges such as the high rate of postoperative recurrence and resistance of some patients to chemotherapy and targeted therapies limit their effectiveness, necessitating the exploration of more effective treatment options. In recent years, immunotherapy, especially immune checkpoint inhibitors(ICIs), has revolutionized NSCLC treatment and significantly improved the survival prognosis of some patients. However, the efficacy of immunotherapy is limited by tumor immune escape, drug resistance, and immune-related adverse events(irAEs), which have not been effectively addressed. Traditional Chinese medicine(TCM), as a traditional therapeutic approach, has shown unique advantages in NSCLC treatment, with studies indicating its ability to enhance immune responses, regulate immune checkpoints, and improve the tumor microenvironment(TME), thus boosting the efficacy of immunotherapy. Additionally, the multi-target and multi-pathway effects of TCM help mitigate the side effects of immunotherapy, further improving efficacy and safety. This review summarizes the latest research progress of TCM in NSCLC immunotherapy, focusing on the research results of TCM in enhancing the effect of immunotherapy by regulating immune cells, optimizing the immune microenvironment, and being applied with ICIs, etc. The latest research progress of TCM in alleviating irAEs is also elucidated. The aim is to provide theoretical support for the clinical application of TCM in the prevention and treatment of NSCLC and the research and development of new drugs and promote the optimization and development of combined immunotherapy and TCM treatment models.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Tumor Microenvironment/drug effects*