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.

Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

Objective To investigate the epidemiological characteristics and changing trend of typhus in Shaanxi Province from 2005 to 2023 to provide a scientific basis for its prevention and control. Methods Excel 2007, SPSS 25.0, Joinpoint 4.9.1.0, and Geoda 1.6 were used for data collection and statistical analysis. Super Map was used for data visualization to describe the changing characteristics of the disease. Results A total of 394 typhus cases were reported in Shaanxi Province from 2005 to 2023. The average annual incidence of typhus was 0.054/100 000, showing a dynamic fluctuation trend(AAPC=-3.3, t=-0.3, P>0.05). The cases were mainly concentrated in Baoji, Hanzhong and Xi′an, accounting for 78.68%. The incidence peak was from May to October, accounting for 64.21% of annual incidence. The epidemic season was from May to October and December. The incidence of the disease was concentrated in the 40-69 age group, accounting for 58.88%, and the sex was 1.07:1. The main occupation was farmers, accounting for 72.08%. The median time from onset to diagnosis was 7 days. Global spatial autocorrelation analysis showed that there were significant spatial autocorrelations in 11 years from 2005 to 2023(P<0.05). Local spatial autocorrelation analysis detected a total of 43“high-high”clustering areas, mainly concentrated in Baoji City. Conclusions The overall incidence of typhus in Shaanxi Province showed a dynamic fluctuation trend, with notable seasonal and regional aggregation. The incidence of typhus was higher in middle-aged and elderly people in rural areas. Surveillance should be strengthened in typhus endemic areas in summer and autumn, and health education should be conducted for key population to form good health habits and reduce the incidence of typhus.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective:To investigate the predictive value of serum 25 hydroxyvitamin D3[25 (OH) D3], insulin-like growth factor 1 (IGF-1) and bone mineral density (BMD) in the occurrence of osteoporosis (OP) in postmenopausal women.Methods:A total of 87 postmenopausal women admitted to Shanxi Children’s Hospital from Jan. 2020 to Dec. 2023 were chosen and separated into OP group ( n=40) and non-OP group ( n=47) . The differences of clinical features, serum 25 (OH) D3, IGF-1 and BMD were compared, and the correlation analysis between serum 25 (OH) D3, IGF-1 and BMD (including L 1-4 BMD, femoral neck BMD and total hip BMD) was analyzed. Multivariate Logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the influencing factors of OP occurrence in postmenopausal women and the predictive value of serum 25 (OH) D3 and IGF-1 combined with BMD for OP occurrence. Results:Compared with non-OP group, there were no significant differences in age, body mass index (BMI) , menopause time, serum calcium, serum phosphorus, alanine aminotransferase (ALT) , or aspartate aminotransferase (AST) levels in OP group ( t=1.42, 1.03, 1.71, 0.93, 0.76, 0.43, 0.04; P=0.161, 0.306, 0.092, 0.354, 0.452, 0.670, 0.966) , but the proportion of diabetes mellitus significantly increased ( χ2=4.37, P=0.037) . Compared with non-OP group, the levels of serum 25 (OH) D3 and IGF-1 and the values of L1-4 BMD, femoral neck BMD and total hip BMD in OP group significantly decreased ( t=5.37, 4.83, 8.31, 2.01, 3.11; P<0.001, P<0.001, P<0.001, P=0.048, P=0.003) . Correlation analysis showed that serum 25 (OH) D3 and IGF-1 were significantly positively correlated with L 1-4 BMD, femoral neck BMD and total hip BMD ( r=0.37, 0.42, 0.29, 0.33, 0.28, 0.29; P<0.001, P<0.001, P=0.024, P=0.015, P=0.032, P=0.021) . Multivariate Logistic analysis showed that serum 25 (OH) D3, IGF-1 and L 1-4 BMD were independent influencing factors for OP occurrence in postmenopausal women ( P=0.007, 0.019, 0.001) ROC curve showed that the area under the curve (AUC) values of serum 25 (OH) D3, IGF-1, L 1-4 BMD and their combination in the prediction of the occurrence of OP in postmenopausal women were 0.764, 0.752, 0.957 and 0.985, respectively. Conclusion:Serum 25 (OH) D3, IGF-1 and L 1-4 BMD can be used as predictors of OP occurrence in postmenopausal women, and the combined value of the three is higher.

Objective:To explore the mechanism by which atractylodin regulates the ROS (reactive oxygen species) /AKT signaling pathway to induce apoptosis and cell cycle arrest in endometrial cancer cells, and to provide theoretical support for its potential application in the treatment of endometrial cancer.Methods:Endometrial cancer cell lines (Ishikawa and HEC-1A) were selected as experimental models. Cells were treated with different concentrations (1, 5, 10, 20 μM) of atractylodin. Cell proliferation was assessed by CCK-8 assay, apoptosis was analyzed by flow cytometry (FCM), and protein expression levels of AKT, p-AKT, Bcl-2, Caspase-3, and other AKT signaling pathway-related proteins were detected by Western blot. ROS levels were measured by flow cytometry.Results:Atractylodin treatment significantly inhibited the proliferation of endometrial cancer cells. Flow cytometry analysis revealed a marked increase in the apoptotic cell population. Western blot results showed that atractylodin treatment significantly decreased p-AKT expression, reduced Bcl-2 protein levels, and increased Caspase-3 expression. ROS level analysis showed that atractylodin treatment significantly elevated intracellular ROS generation, suggesting that atractylodin might induce AKT pathway inhibition through ROS, leading to cell cycle arrest and apoptosis.Conclusions:Atractylodin regulates the ROS/AKT signaling pathway to induce apoptosis and cell cycle arrest in endometrial cancer cells, exhibiting potential anti-endometrial cancer effects. This study provides new theoretical evidence for the application of atractylodin in the treatment of endometrial cancer and reveals its underlying mechanisms.

Objective:To compare the clinical outcomes of arthroscopic Y-shaped suture suspension fixation and those of open reduction and internal fixation in the treatment of tibial insertion avulsion fractures of the posterior cruciate ligament (PCL).Methods:A retrospective study was conducted to analyze the clinical data from the 23 patients with PCL tibial avulsion fracture who had been admitted to Department of Sports Medicine, The Affiliated Changsha Central Hospital, University of South China, from May 2018 to May 2024. There were 15 males and 8 females with an age of (39.0±15.6) years. By the Meyers-McKeever classification, there were 20 cases of type Ⅱ and 3 cases of type Ⅲ. All patients were divided into 2 groups based on their different surgical schemes: an arthroscopic group of 11 cases treated with Y-shaped suture suspension fixation under arthroscopy and an open group of 12 cases treated with open reduction and internal fixation. The surgical time, intraoperative blood loss, and visual analog scale (VAS) pain scores, Lysholm knee function scores, and International Knee Documentation Committee (IKDC) subjective scores at 1 month after surgery and the last follow-up were recorded and compared between the 2 groups.Results:There was no statistically significant difference in the preoperative general information between the 2 groups, indicating comparability ( P>0.05). The 23 patients were followed up for (13.7±3.8) months after surgery. None of the patients experienced complications like incision infection, neurovascular damage, nonunion or delayed union of fracture. In the arthroscopic group, the surgical time was (97.1±11.1) min, significantly shorter than that in the open group [(64.7±9.0) min], and the intraoperative blood loss (14.9±6.6) mL, significantly less than that in the open group [(29.4±13.2) mL] ( P<0.05). At 1 month after surgery, the VAS pain score, Lysholm knee function score, and IKDC subjective score in the arthroscopic group were, respectively, 3.0 (2.0, 3.0) points, (72.0±4.8) points, and (67.3±2.9) points, all significantly better than those in the open group [5.0 (4.0, 5.0) points, (66.9±4.0) points, and (63.1±2.4) points] ( P<0.05). There was no statistically significant difference in the VAS pain score, Lysholm knee function score, or IKDC subjective score at the last follow-up between the 2 groups ( P>0.05). Conclusions:Both arthroscopic Y-shaped suture suspension fixation and open reduction and internal fixation can achieve satisfactory treatment outcomes for PCL tibial avulsion fractures. The latter shows an advantage in shorter surgical time, but the former advantages in less bleeding volume and better early efficacy.

Objective:To evaluate the design methodology and efficacy of skin excision in sitting and supine positions of blepharoplasty.Methods:A retrospective study was performed on 31 female patients who received double eyelid surgery at the Department of Plastic and Aesthetic Surgery, Affiliated Hospital of Qingdao University, from January to June 2021. The patients ′ ages varied from 18 to 37 years, with a mean age of (26.5±5.2) years. Of the patients, 27 exhibited single eyelids, while 4 presented with shallow double eyelids. All patients demonstrated laxity of the upper eyelid skin. The method of utilizing the sitting and supine positions was employed to determine the extent of skin excision, subsequently leading to full-incision double eyelid surgery. Follow-up was performed through clinic visits and WeChat to monitor double eyelid morphology, complications, and evaluate patient satisfaction. Results:All 31 patients successfully underwent the surgical procedure. Postoperative follow-up duration varied from 3 to 12 months. The double eyelid lines manifested as natural and seamless, with suitable width. All patients exhibited satisfactory eyelid closure, with no instances of ectropion or incomplete eyelid closure. Skin laxity of the upper eyelid was significantly ameliorated in all instances. The patient satisfaction rate was 100% (31/31).Conclusions:The sitting and supine position for executing skin excision in double eyelid surgery is straight forward to implement. Postoperative outcomes demonstrate natural and seamless double eyelid contours, with adequate rectification of upper eyelid skin laxity.

Objective:To observe the effect of hyperthermia combined with iron overload on the regulation of tumor-associated macrophage polarization and the migration ability of CAL-27 cells and explore its mechanism.Methods:Human monocytic leukemia cell THP-1 was induced and polarized into M2 macrophages. M2 tumor-associated macrophages and CAL-27 cells were divided into the control group (no intervention), hyperthermia group (incubated at 42 ℃ for 1 h, and then incubated at 37 ℃ for 24 h), ferric citrate group (added with 2.5 mg/ml ferric citrate, and cultured in an incubator at 37 ℃for 24 h) and hyperthermia + ferric citrate group (added with 2.5 mg/ml ferric citrate for 1 h, cultured in an incubator at 42℃ for 1 h, and then incubated at 37℃ for 24 h). For M2 macrophage groups, the mRNA relative expression levels of surface markers of M1 macrophage polarization including interleukin (IL)-1β, tumor necrosis factor-α(TNF-α), and those of M2 macrophage polarization including IL-10 and transforming growth factor-β(TGF-β) were detected by real-time reverse transcription polymerase chain reaction. The expression levels of IL-1β and IL-10 were detected by ELISA. The expression levels of CD86 (surface marker of M1 macrophage polarization) and CD206 (surface marker of M2 macrophage polarization) were measured by flow cytometry. The expression levels of signal transducer and activator of transcription 3 (STAT3), Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) and phosphorylated (p)-NF-κB were detected by Western blot (WB). The migration ability of CAL-27 cells was assessed by scratch assay.Results:Compared with the control group, the expression levels of IL-1βand TNF-α mRNA, and IL-1βand CD86 proteins were up-regulated, whereas those of IL-10 and TGF-β mRNA, and IL-10 and CD206 proteins were down-regulated in the hyperthermia, ferric citrate and hyperthermia + ferric citrate groups, respectively (all P<0.05). In addition, the changes in the hyperthermia+ferric citrate group were significantly larger than those in the hyperthermia and ferric citrate groups (all P<0.05). WB showed that the expression level of STAT3 protein was down-regulated and those of TLR4, NF-κB and p-NF-κB expression were up-regulated in the hyperthermia + ferric citrate group (all P<0.05). Scratch assay showed that the migration ability of CAL-27 cells was inhibited in the hyperthermia, ferric citrate and hyperthermia + ferric citrate groups ( P<0.001), and the changes in the hyperthermia + ferric citrate group were significantly more pronounced than those in the hyperthermia and ferric citrate groups (both P<0.001). Conclusions:Hyperthermia and iron overload can promote the polarization of M1 macrophages and inhibit the polarization of M1 macrophages into M2 macrophages, thereby suppressing the migration of oral squamous cell carcinoma. The mechanism may be related to inhibiting the expression of STAT3 and activating the TLR4/NF-κB signaling pathway.