In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Esophageal cancer is one of the most prevalent malignant tumors globally.Its clinical management is challenged by difficulties in early diagnosis,significant inter-individual variability in therapeutic efficacy,and high rates of tumor residuals and recurrence.Circulating tumor DNA(ctDNA),a novel liquid biopsy biomarker,reflects tumor burden and genetic characteristics.It offers advantages such as non-invasiveness,repeatability,and real-time dynamic monitoring,pro-viding a promising approach for precision diagnosis and treatment of esophageal cancer.In recent years,ctDNA has shown remarkable progress in the early detection,efficacy prediction,prognos-tic assessment,and monitoring of tumor residuals and recurrence in esophageal cancer,emerging as an essential tool in the clinical management of the disease.This review summarizes the latest advancements in ctDNA research in esophageal cancer,providing valuable insights and inspiration for future studies and clinical applications.

Objective To establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

Objective To investigate the protective mechanisms of huanglian jiedu decoction(HLJDD)against hypertensive cardiac hypertrophy(HCH)in rats.Methods The HCH model was constructed in SD rats through abdominal aortic constriction(AAC).Rats were randomly divided into the sham operation(Sham)group,model(Mod)group,Mod+HLJDD high,medium and low-dose(Mod+H,Mod+M,Mod+L)groups,and Mod+Captopril(Cap)group using a simple random sampling method.Blood pressure,echocardiography,hematoxylin-eosin staining,and Masson staining were performed to assess the impact of HLJDD on HCH.Based on the results of part one,rats were further randomly divided into Sham group,Mod group,Mod+Notch1 inhibitor(DAPT)group,Mod+Notch1 agonist(Jagged-1)group,Mod+HLJDD high-dose(HLJDD)group,Mod+HLJDD high-dose+Notch1 inhibitor(DAPT+H)group,and Mod+HLJDD high-dose+Notch1 agonist(Jagged-1+H)group using a simple random sampling method.Hematoxylin-eosin staining and Masson staining were observed.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to detect the expression levels of related inflammatory factors,to further explore the mechanisms of HLJDD.Results Compared with the Mod group,rats in the Mod+H group exhibited reduced blood pressure(P＜0.05),improved cardiac func-tion(P＜0.05),relieved myocardial injury and decreased myocardial fibrosis(P＜0.05).Compared with the Mod group,the DAPT group displayed aggravated myocardial injury and fibrosis,decreased expression levels of Notch1 and Hes1(P＜0.05),and increased ex-pression levels of inflammatory factors and NF-κB p65(P＜0.05).The Jagged-1 group and HLJDD group showed opposite results.Compared with HLJDD group,the DAPT+H group displayed aggravated myocardial injury and fibrosis,decreased expression levels of Notch1 and Hes1(P＜0.05,P＜0.01),and increased expression levels of inflammatory factors and NF-κB p65(P＜0.05).The Jag-ged-1+H group showed opposite results,indicating that HLJDD can partially activate the Notch1signaling pathway while inhibiting the NF-κB signaling pathway and the release of inflammatory factors.Conclusion HLJDD can alleviate AAC-induced HCC in rats,and its mechanism may be achieved through the modulation of the Notch1/NF-κB signaling pathway.Additionally,a certain negative feed-back regulatory relationship exists between the Notch1 signaling pathway and the NF-κB signaling pathway.

Objective To study the age-dependent relationship between body mass index(BMI)and cognitive impairment in rural population aged 40 years and above.Methods From October 2014 to March 2015,people aged 40 years and above,who lived in two natural villages in Huyi District of Xi'an,were selected as the research subjects.Their general demographic information,lifestyle,medical history,family history,physical examination,and biochemical examination were collected.Mini-Mental State Examination(MMSE)was used to evaluate global cognitive function.Cognitive impairment was defined as an MMSE score lower than the cutoff value,specifically,scores ≤17 for subjects who were illiterate,scores ≤20 for subjects with primary school education,and scores ≤24 for subjects with junior high school education or above.The age-dependent relationship between BMI and cognitive impairment was discussed using stratified analysis,restricted cubic spline(RCS),and multivariate Logistic regression.Results We included a total of 1 792 subjects in the analysis,of whom 230(12.8％)were diagnosed with cognitive impairment.There were 726 males(40.5％);the average age was(55.53±9.92)years,ranging from 40 to 85 years,1 193 subjects aged 40-59 years(66.6％),and 599 subjects aged ≥60 years(33.4％).The average BMI was(25.29±3.14)kg/m2.In the total population,BMI index was fitted as restricted cubic splines in the Logistic regression model,and other confounding factors were corrected.The results showed that BMI index was significantly correlated with cognitive impairment(Poverall=0.023),and there was a trend of nonlinear relationship(P nonlinear=0.097).The specific relationship was that with BMI=25 kg/m2 as the reference(OR=1),when BMI index was＜25 kg/m2,the OR value increased as BMI index decreased.However,when BMI index was ≥25 kg/m2,the OR value did not change significantly as BMI index increased.The population was divided into two subgroups according to age(40-59 years vs.≥60 years).Stratified analysis showed that in the ≥60 years old subgroup,cognitive impairment had significant correlation with BMI index(Poverall=0.038,Pnonlinear=0.097),and the changing trend of the correlation was similar to that of the overall population.By contrast,in the 40-59 years old subgroup,BMI index was not significantly associated with cognitive impairment(Poverall=0.722,Pnonlinear=0.738).Conclusion The relationship between BMI and cognitive impairment is affected by age.No significant association is found in the middle-aged population of 40-59 years old,but there may be a nonlinear association in the elderly population over 60 years old.Specifically,with BMI=25 kg/m2 as the boundary,as BMI decreases,the risk of cognitive impairment gradually increases.As BMI further increases,the risk of cognitive impairment does not change significantly even though it reaches the obesity level.

A 36-year-old male developed unconsciousness and no response to voice stimuli after taking approximately 2 050 mg felodipine (the specific time was unknown). Two hours later, he was sent to the department of emergency by his family and admitted to the hospital. His vital signs showed body temperature 35.1 ℃, pulse 148 times/min, respiration 32 times/min, and blood pressure 65/34 mmHg. Acute drug poisoning, acute toxic cardiomyopathy, acute toxic shock, acute type Ⅱ respiratory failure, acute toxic encephalopathy, and acute renal failure were diagnosed based on the patient′s clinical manifestations combined with laboratory tests results, cardiac ultrasound, chest and abdominal CT scans. Endotracheal intubation connected to a ventilator for invasive assisted ventilation, pressure boosting, and fluid resuscitation were given. At the same time, repeated gastric lavage and enema were performed to remove toxins. Blood perfusion was intermittently and repeatedly administered, and continuous renal replacement therapy was used. The blood concentration of felodipine was 1 298 μg/L at 2 hours after admission, and cardiac arrest occurred at 4 hours. Venous-arterial extracorporeal membrane oxygenation (V-A ECMO) treatment was administered immediately. After 48 hours of ECMO operation, sedatives were discontinued and the patient′s consciousness was improved after 4 hours. On the 5th day of ECMO treatment, his heart rate was 72 beats per minute, and blood pressure was 127/65 mmHg. The blood concentration of felodipine decreased to 2 μg/L. The patient′s vital signs were significantly improved and ECMO supportive treatment was withdrawn. After 26 days of hospitalization, the patient recovered and was discharged.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

Esophageal cancer is one of the most prevalent malignant tumors globally.Its clinical management is challenged by difficulties in early diagnosis,significant inter-individual variability in therapeutic efficacy,and high rates of tumor residuals and recurrence.Circulating tumor DNA(ctDNA),a novel liquid biopsy biomarker,reflects tumor burden and genetic characteristics.It offers advantages such as non-invasiveness,repeatability,and real-time dynamic monitoring,pro-viding a promising approach for precision diagnosis and treatment of esophageal cancer.In recent years,ctDNA has shown remarkable progress in the early detection,efficacy prediction,prognos-tic assessment,and monitoring of tumor residuals and recurrence in esophageal cancer,emerging as an essential tool in the clinical management of the disease.This review summarizes the latest advancements in ctDNA research in esophageal cancer,providing valuable insights and inspiration for future studies and clinical applications.

Objective To study the age-dependent relationship between body mass index(BMI)and cognitive impairment in rural population aged 40 years and above.Methods From October 2014 to March 2015,people aged 40 years and above,who lived in two natural villages in Huyi District of Xi'an,were selected as the research subjects.Their general demographic information,lifestyle,medical history,family history,physical examination,and biochemical examination were collected.Mini-Mental State Examination(MMSE)was used to evaluate global cognitive function.Cognitive impairment was defined as an MMSE score lower than the cutoff value,specifically,scores ≤17 for subjects who were illiterate,scores ≤20 for subjects with primary school education,and scores ≤24 for subjects with junior high school education or above.The age-dependent relationship between BMI and cognitive impairment was discussed using stratified analysis,restricted cubic spline(RCS),and multivariate Logistic regression.Results We included a total of 1 792 subjects in the analysis,of whom 230(12.8％)were diagnosed with cognitive impairment.There were 726 males(40.5％);the average age was(55.53±9.92)years,ranging from 40 to 85 years,1 193 subjects aged 40-59 years(66.6％),and 599 subjects aged ≥60 years(33.4％).The average BMI was(25.29±3.14)kg/m2.In the total population,BMI index was fitted as restricted cubic splines in the Logistic regression model,and other confounding factors were corrected.The results showed that BMI index was significantly correlated with cognitive impairment(Poverall=0.023),and there was a trend of nonlinear relationship(P nonlinear=0.097).The specific relationship was that with BMI=25 kg/m2 as the reference(OR=1),when BMI index was＜25 kg/m2,the OR value increased as BMI index decreased.However,when BMI index was ≥25 kg/m2,the OR value did not change significantly as BMI index increased.The population was divided into two subgroups according to age(40-59 years vs.≥60 years).Stratified analysis showed that in the ≥60 years old subgroup,cognitive impairment had significant correlation with BMI index(Poverall=0.038,Pnonlinear=0.097),and the changing trend of the correlation was similar to that of the overall population.By contrast,in the 40-59 years old subgroup,BMI index was not significantly associated with cognitive impairment(Poverall=0.722,Pnonlinear=0.738).Conclusion The relationship between BMI and cognitive impairment is affected by age.No significant association is found in the middle-aged population of 40-59 years old,but there may be a nonlinear association in the elderly population over 60 years old.Specifically,with BMI=25 kg/m2 as the boundary,as BMI decreases,the risk of cognitive impairment gradually increases.As BMI further increases,the risk of cognitive impairment does not change significantly even though it reaches the obesity level.