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.

ObjectiveTo investigate the ability of clinically isolated， Helicobacter pylori （H. pylori）-specific gene polymerase chain reaction （PCR）-positive gastric， vaginal， and fecal Candida to release H. pylori. MethodsResuscitate 4 strains of H. pylori -specific 16S rDNA and ureA gene PCR-positive Candida strains isolated in laboratory from clinical sources， including 1 strain of gastric Candida， 1 strain of fecal Candida， 2 strains of vaginal Candida and the standard Candida albicans strain ATCC10231 （Ca10231）. The presence of H. pylori-specific ureA in the 5 strains of Candida isolates was confirmed by PCR. The aforementioned strains of Candida and H.pylori were inoculated into urea medium and cultured in a constant temperature incubator at 37 ℃. The color change of the medium was observed daily. A change in the medium's color from yellow to red indicated the presence of urease activity. Then， the five strains of Candida and H. pylori were co-incubated with the magnetic beads coated with H. pylori antibodies respectively. Scanning electron microscopy （SEM） was employed to observe the presence of bacilli adsorbed on the surface of the magnetic beads. PCR was used to detect the presence of H.pylori-specific 16S rDNA and ureA genes on magnetic beads. ResultsThe PCR analysis of the ureA gene in the four Candida isolates was positive， whereas the Ca10231 strain tested negative. Upon culturing the four Candida isolates on urea medium， the medium color changed from yellow to red which was determined to be urease positive， while the medium containing Ca10231 remained unchanged， which was urease negative. SEM revealed that bacilli could be observed on the surface of magnetic beads co-incubated with the 4 strains of Candida of clinical origin and H.pylori isolate. Specifically， PCR testing of the magnetic beads co-incubated with one vaginal Candida， one gastric Candida and H.pylori isolate showed positive results for the 16S rDNA and ureA genes of H. pylori； however， the PCR tests for the two genes were negative for the magnetic beads co-incubated with the other two Candida isolate. ConclusionThis study demonstrates that H. pylori-specific genes Candida can release H. pylori.

ObjectiveTo compare the differences between wild Alpiniae Oxyphyllae Fructus（WAOF） and cultivated Alpiniae Oxyphyllae Fructus（CAOF） through a traditional quality evaluation system for medicinal materials. MethodsA total of 10 batches of WAOF and 12 batches of CAOF samples were collected from various regions of Hainan province. Relevant analytical methods from the 2020 edition of the Pharmacopoeia of the People's Republic of China were employed to observe the characteristics of WAOF and CAOF， followed by microscopic identification， thin-layer chromatography（TLC） identification， moisture content（toluene method）， total ash， acid-insoluble ash， water-soluble and alcohol-soluble extracts（hot dipping method）， water-soluble protein， total polysaccharides and total flavonoids（ultraviolet spectrophotometry）， and volatile oil content（method A under general rule 2204）. The contents of five active components（protocatechuic acid， chrysin， kaempferol， tectochrysin and nootkatone） were quantified using ultra-performance liquid chromatography（UPLC）， and the antioxidant activity was evaluated. Building upon traditional quality evaluation of AOF， quantitative measurements were conducted on its appearance traits including diameter， length， plumpness（diameter/length ratio）， and color. Canonical correlation analysis was performed using SPSS 26.0 to explore relationships between appearance traits and intrinsic quality. ResultsNo significant differences were observed between WAOF and CAOF in microscopic observation， TLC identification， moisture content， protocatechuic acid content， kaempferol content， odor， or antioxidant activity measured by 2，2ʹ-azino-bis（3-ethylbenzothiazoline-6-sulfonic acid）（ABTS） method. WAOF exhibited significantly higher levels in water-soluble extracts， alcohol-soluble extracts， total polysaccharide content， water-soluble protein content， 100-grain weight， length， and total color difference（ΔE^*ab） compared to CAOF（P<0.01）. In contrast， CAOF showed significantly higher levels of total ash， acid-insoluble ash， content of total flavonoids， volatile oil content， chrysin content， tectochrysin content， nootkatone content， diameter， plumpness， lightness（L^*）， red-green chromaticity（a^*）， yellow-blue chromaticity（b^*）， and antioxidant activity measured by 1，1-diphenyl-2-picrylhydrazyl（DPPH） method compared to WAOF（P<0.01）. Correlation analysis between 7 phenotypic traits and 8 quality traits revealed that among the phenotypic traits， plumpness， L^*， a^*， and b^* exerted significant influence on intrinsic quality. Among the quality traits， total flavonoids， volatile oils， nootkatone， chrysin， and tectochrysin contributed substantially to intrinsic quality. ConclusionPlumpness， L^*， a^*， and b^* of AOF significantly influence its intrinsic quality， and higher values of these parameters indicate relatively superior intrinsic quality. The comprehensive quality evaluation reveals that CAOF samples collected in this study are superior to their wild counterparts.

ObjectiveTo investigate whether anti-programmed death-1 （PD-1） monoclonal antibody can enhance the efficacy and safety of argon-helium cryoablation combined with targeted therapy in patients with unresectable hepatocellular carcinoma （uHCC） aged 60 years or older. MethodsA retrospective analysis was performed for the clinical data of 124 patients with advanced uHCC aged 60 years or older who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to September 2024. After propensity score matching， 57 patients received cryoablation combined with targeted therapy （double combination group）， while 57 received cryoablation combined with targeted therapy and anti-PD-1 monoclonal antibody （triple combination group）. The indicators for efficacy assessment included objective response rate （ORR）， disease control rate （DCR）， progression-free survival （PFS）， overall survival （OS）， and the incidence rate of adverse events. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. A Cox proportional-hazards regression model analysis was used to investigate the influencing factors for survival prognosis. ResultsThe triple combination group had a significantly higher ORR than the double combination group （59.6% vs 29.8%， χ²=9.083， P=0.003）， while there was no significant difference in DCR between the two groups （87.7% vs 77.2%， χ²=1.516， P=0.218）， and compared with the double combination group， the triple combination group had significantly longer median PFS （9.1 months vs 4.8 months， χ²=7.813， P=0.005） and median OS （26.1 months vs 13.6 months， χ²=14.199， P<0.001）. The multivariate Cox proportional-hazards regression model analysis showed that triple combination treatment was an independent influencing factor for PFS （hazard ratio ［HR］=0.52， 95% confidence interval ［CI］： 0.35 — 0.78， P=0.001） and OS （HR=0.32， 95%CI： 0.20 — 0.51， P<0.001）. There was no significant difference in the incidence rate of adverse events between the two groups （P>0.05）. ConclusionTriple combination treatment with argon-helium cryoablation， targeted therapy， and anti-PD-1 monoclonal antibody can significantly improve survival benefits in uHCC patients aged 60 years or older， with a controllable safety profile.

ObjectiveTo explore the potential categories and characteristics of the public hospice care demand in Hainan Province， and analyze different potential types of influencing factors， so as to provide reference for relevant departments to improve the public awareness and demand of hospice care. MethodsUsing convenience sampling method， select 6484 cities of the public as the survey object， using the general data questionnaire， the hospice care demand questionnaire of the potential profile analysis， and analyze the influencing factors of the public hospice care demand category. ResultsThe characteristics of the hospice care demand in Hainan Province were divided into three potential categories： low demand group （14.19%）， medium demand group （49.99%） and high demand group （35.82%）. Multivariate analysis showed that gender， age， education level， cultural belief， and life-death education experience were the main influencing factors of public hospice care demand （p<0.05）. Males， those aged 41-60 years， and those with high school education or below had relatively lower hospice care demand， while those with life-death education experience had relatively higher demand. ConclusionRelevant departments should focus on hospice care knowledge popularization and demand enhancement for males， middle-aged groups， and people with low education levels， while strengthening universal life-death education through stratified and classified publicity strategies and educational interventions to improve different populations’ awareness and acceptance of hospice care.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

Objective To investigate the association between depression and autonomic nervous function in Parkinson disease （PD）， and to provide a basis for clinical treatment. Methods Clinical and neurocirculation data were collected from 168 PD patients who attended Department of Neurology， The Second Affiliated Hospital of Hainan Medical College， from July 2022 to July 2023， and according to the score of Beck Depression Inventory， the patients were divided into depression in PD （dPD） group with 57 patients and non-dPD （nPD） group with 111 patients. General clinical data were collected from all patients. The supine-to-standing TCD test was performed for all patients to record systolic blood pressure （SBP）， diastolic blood pressure （DBP）， heart rate （HR）， and the mean velocity （Vm）， pulsatility index （PI）， and resistance index （RI） of the middle cerebral artery （MCA） at 1， 3， and 5 minutes in both the supine and standing positions. A network was constructed for depression symptoms in PD. Results In the network of non-motor symptoms in PD， depression showed the highest centrality and the strongest predictability and was strongly correlated with sleep/fatigue and mood/cognition， with a strength centrality stability coefficient （CS strength） of 0.440. Compared with the nPD group， the dPD group had significantly lower supine HR， ∆HR， Vm in the standing position， and ∆Vm%， a significantly greater ∆DBP， and a significantly higher proportion of patients with dizziness with orthostatic hypotension or orthostatic cerebral hypoperfusion （P<0.05）. Depression was positively correlated with ∆SBP， ∆DBP， Vm in the supine position， and RI in the standing position， and it was negatively correlated with ∆HR， DBP in the supine position， HR in the supine position， and ∆PI （CS strength=0.375 and 0.222）. Conclusion Impairment of cardiovascular and cerebral autonomic nervous function might be involved in the pathogenesis of depression in PD， and intervention of depression can help improve the overall non-motor symptoms of PD， with sleep， fatigue， and cognition as the effective targets for improving depression in PD.
Parkinson Disease ; Depression

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.