Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

ObjectiveTo elucidate the effects of autonomic neuromodulators [calcium chloride (CaCl₂)-acetylcholine (ACh)] on atrial electrical remodeling and histopathological changes in rats, thereby providing evidence for further investigation into the pathological mechanisms by which autonomic imbalance induces atrial fibrillation (AF). MethodsTen 8-week-old male Sprague-Dawley (SD) rats were randomly divided into experimental and control groups, with 5 rats in each group. The experimental group received daily tail vein injections of a CaCl₂-ACh mixed solution for 28 days, while the control group received an equal volume of saline. Surface electrocardiograms were recorded before and after daily administration. On day 28 of administration, under isoflurane inhalation anesthesia, echocardiography was performed, and then the rats were euthanized by exsanguination under isoflurane anesthesia for tissue collection. Body weight and heart weight of rats were measured, and electrophysiological parameters including AF inducibility, conduction velocity, and conduction dispersion in isolated rat hearts were monitored using the MappingLab multichannel electrophysiological mapping system. HE staining was performed to evaluate atrial tissue architecture and inflammatory cell infiltration. The expression levels of matrix metalloproteinase 9 (MMP-9) and interleukin-1 beta (IL-1β) were analyzed by Western blotting. Masson staining was used to quantitatively analyze the proportional distribution of collagen fibers and myocardial fibers, and to calculate the area of collagen deposition, thereby evaluating the degree of myocardial fibrosis. Wheat germ agglutinin (WGA) staining was used to evaluate morphological changes of cardiomyocytes. Dihydroethidium (DHE) staining was used to detect the level of oxidative stress in atrial myocytes. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect atrial cell apoptosis. ResultsCompared with the control group, the experimental group showed obvious arrhythmias on electrocardiograms. Echocardiography after 28 days of administration revealed significant structural remodeling in the experimental group, with a marked increase in left atrial anteroposterior diameter (P < 0.05), and also showed cardiac dysfunction, with significant decreases in left ventricular ejection fraction and left ventricular fractional shortening (P < 0.01). Compared with the control group, the experimental group showed a significantly increased heart weight-to-body weight ratio (P < 0.05), a markedly higher AF inducibility (P < 0.001), a significantly slowed atrial conduction velocity (P < 0.05), an uneven isochronal map with irregular directions, and a significantly increased conduction dispersion (P < 0.01). HE staining showed that atrial myocytes in the experimental group were disorganized, with slight inflammatory cell infiltration. Western blotting showed that the expression levels of MMP-9 and IL-1β in the atrial tissue of the experimental group were significantly upregulated (P < 0.05). Masson staining showed a significant increase in collagen deposition and a significant increase in fibrosis area in the atrial tissue of the experimental group (P < 0.001). WGA staining showed that cardiomyocytes in the experimental group were significantly hypertrophied compared with the control group (P < 0.05). DHE staining and TUNEL staining revealed that the level of oxidative stress in atrial myocytes (P < 0.001) and the apoptotic rate (P < 0.01) were both significantly increased. Conclusion Daily tail vein injections of the autonomic neuromodulator CaCl₂-ACh mixed solution for 28 days can successfully induce AF in rats, accompanied by significant atrial structural remodeling, electrical remodeling, and oxidative stress.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

Objective To evaluate the prevention and control effectiveness of four major chronic diseases in Youyang County, and find the weak link of prevention and control, and to provide theoretical support for improving prevention and control strategies. Methods Based on the death data of permanent residents from 2012 to 2020 extracted from the cause-of-death registration and reporting system of Youyang County, a statistical analysis was conducted using SPSS19.0. The annual percentage change (APC) was tested by t-test. Results From 2012 to 2020, the mortality rate of and the standardized mortality rate of the four major chronic diseases and the premature mortality rate of diabetes in males showed an increasing trend (APC was 3.05%, 1.82% and 27.12%, respectively, P < 0.05). The mortality rate of the four chronic diseases in females increased (APC was 2.53%, P < 0.05), while the proportion of premature death of the four chronic diseases and the probability of premature death of cardiovascular and cerebrovascular diseases in females decreased (APC was -2.37%, -5.73%, P < 0.05). The standardized mortality rate and premature death rate of the four major chronic diseases were higher in males than those in females. The mortality rate of the four major chronic diseases and the premature death rate of diabetes in the whole population were on the rise (APC was 2.84% and 12.86%, P < 0.05). It was expected that the early death probability of the four major chronic diseases in Youyang County would be 12.65% in 2030, higher than the target value of 12.59% of ^“Healthy China 2030^”. Conclusion The future focus of Youyang County is to prevent and control malignant tumors and diabetes, especially to strengthen the prevention and control of male diabetes.

ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway， and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups： blank control， model， low-， medium-， and high-dose （7.03， 14.06， 28.12 g·kg^-1， respectively） Bugansan， and vitamin E （suspension， 27 mg·kg^-1）， with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose （400 mg·kg^-1）， while the blank control group was injected with normal saline. Since the day of modeling， rats in intervention groups received corresponding agents by gavage， and those in blank control and model groups received an equal volume of normal saline （10 mL·kg^-1）. General biological features such as fur color， activity， body mass， water intake， and food intake were observed. Meanwhile， the content of malondialdehyde （MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in the serum were measured to assess aging. Grip strength and the content of total bile acids （TBA） and the activity of α-amylase （AMY） in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase （β-gal） in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 （GLP-1）， vasoactive intestinal peptide （VIP）， and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 （Bmi1） and leucine-rich repeat-containing G protein-coupled receptor 5 （Lgr5） in the duodenal tissue. Moreover， Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to quantify the mRNA levels of Ki67， Bmi1， and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally， the mRNA levels of R-spondin1， Wnt3a， β-catenin， and glycogen synthase kinase-3β （GSK-3β） and the protein levels of R-spondin1， Wnt3a， β-catenin， and phosphorylated GSK-3β （p-GSK-3β） in the duodenum were determined by Real-time PCR and Western blot， respectively， to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group， the model group showed decreases in body mass， water intake， food intake， grip strength， activities of SOD， GSH-Px， and AMY in the serum and content of GLP-1， VIP and D-xylose in the serum （P<0.05）， increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）， reductions in villus length， villus width， crypt depth， and villi/crypt （V/C） value， down-regulated mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and up-regulated level of GSK-3β， phosphorylation （p）-GSK-3β （P<0.05）. Compared with the model group， Bugansan increased the body mass， water intake， food intake， grip strength， and activities of SOD， GSH-Px， and AMY and levels of GLP-1， VIP and D-xylose in the serum （P<0.05）， while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）. Furthermore， Bugansan increased the villus length， villus width， crypt depth， and V/C value， up-regulated the mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and down-regulated the level of GSK-3β and p-GSK-3β （P<0.05）. ConclusionAging rats exhibit obvious impairments in digestion and absorption functions， accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions， ultimately contributing to the delay of aging.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

Objective To explore the influencing factors on foot function recovery after distraction device-assisted repositioning of small incisions treatment for Sanders Ⅱ and Ⅲ calcaneal fractures,and to provide guidance for timely clinical interventions.Methods A retrospective analysis was conducted on 80 patients with Sanders type Ⅱ and Ⅲ calcaneal fractures admitted to the People's Hospital of Bozhou from January 2021 to June 2023.Data were collected using a general information questionnaire,the hospital's electronic medical record system,the visual analog scale(VAS),the Marland foot function scale(MFS),the perceived social support scale(PSSS),and the perceived stress scale(PSS).The influencing factors of postoperative foot function recovery were analyzed using univariate factor analysis,multivariate linear regression,and structural equation modeling.Results The MFS scores of 80 patients at 6 months post-operation were significantly higher than preoperative scores(P＜0.001).The rates of excellent,good,fair,and poor foot function at 6 months post-operation were 56.3％,31.3％,10.0％,and 2.5％,respectively.Univariate analysis revealed significant differences in MFS scores based on different ages,time to start full weight-bearing exercise,bone mineral density,surgical timing,body mass index(BMI),postoperative VAS score,PSSS score,PSS score,and the presence of postoperative peroneal muscle spasm and peroneal muscle tendon adhesion(P＜0.05).Multivariate linear regression identified age,time to start full weight-bearing exercise,surgical timing,BMI,postoperative fibular muscle spasm,postoperative fibular muscle tendon adhesion,postoperative VAS score,PSSS score,and PSS score as significant factors affecting foot function recovery(P＜0.05).Structural equation modeling indicated that age,time to start full weight-bearing exercise,bone density,operative timing,BMI,postoperative peroneal muscle spasm,postoperative peroneal tendon adhesion,and pain severity directly influenced postoperative foot functional recovery.Additionally,psychological stress not only directly affected postoperative foot functional recovery but also indirectly influenced it through the mediating effect of social support.Conclusions Foot function recovery after surgery for Sanders type Ⅱ and Ⅲ calcaneal fractures is influenced by multiple factors.Psychological stress not only directly affects the recovery of foot function after surgery,but also mitigates the harm to foot function through social support.

Total knee arthroplasty(TKA)is mainly used for the treatment of advanced knee osteoarthritis.Accurate preoperative planning and rapid prosthesis recognition are essential for smooth operation and postoperative rehabilitation.However,manual prosthesis recognition rely on doctors'experience,easily leading to misdiagnosis or missed diagnosis.Recent years,artificial intelligence(AI)had been integrated with medical imaging,represented by machine learning(ML)and its branch deep learning(DL),and displayed relatively powerful auxiliary functions in TKA.The research status and application progresses of AI combined with imaging in TKA were reviewed in this article.

Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.