Objective To understand the antibody levels of diphtheria and tetanus among healthy population in Shanghai Pudong New Area, and to provide a scientific basis for improving the vaccine immunization strategy. Methods Random sampling was used to select healthy people of all ages in 16 communities in Shanghai Pudong New Area from 2018 to 2024, and serum samples were collected and tested for serum anti-diphtheria and tetanus toxin IgG antibodies by enzyme-linked immunosorbent assay (ELISA) method to analyze the antibody positivity rate (≥0.1 IU/ml) and the geometric mean concentration (GMC) of antibodies. Results A total of 3 312 serum samples were included, with a male-to-female ratio of 0.76:1, and 53.77% were local residents. The seropositivity rates and geometric mean concentrations (GMC) of both diphtheria and tetanus antibodies generally declined with increasing age, but exhibited a transient rebound in the 7y-. A total of 1 175 individuals (35.48%) were seropositive for diphtheria, with a GMC of 0.054 IU/mL. For tetanus, 988 individuals (29.83%) were seropositive, with a GMC of 0.033 IU/mL. Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1 324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1 142.007) were observed among different age groups (P<0.001). Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1142.007) were also found across different years (P<0.001). Conclusion The prevalence of diphtheria and tetanus antibodies in the healthy population of Pudong New Area is relatively low, particularly among adults over 20 years of age with inadequate immunization. This underscores the need to reinforce the National Immunization Program (NIP) vaccine specifications for children under 6 years of age and implement an immunization strategy for adolescents or adults against diphtheria and tetanus.

ObjectiveThis study sought to investigate the impact of exosomes derived from LoVo cells (LoVo-Exos) in colorectal cancer (CRC) on tumor angiogenesis, as well as to elucidate the potential molecular mechanisms underlying their pro-angiogenic effects. MethodsLoVo-Exos were isolated via ultracentrifugation, and their internalization into recipient human umbilical vein endothelial cells (HUVECs) was visualized using confocal microscopy. The influence of LoVo-Exos on angiogenesis was assessed through an in vitro tube formation assay. Additionally, the pro-angiogenic effects of LoVo-Exos were evaluated in vivo using a matrix gluing assay in mice. To investigate the molecular mechanisms through which LoVo-Exos facilitate angiogenesis, Western blot analysis was employed to examine the transfer of pEGFR by LoVo-Exos into recipient cells. Both Western blot and ELISA were utilized to assess the expression levels of key signaling proteins within the EGFR-ERK pathway, as well as the expression of downstream angiogenic core molecules. Furthermore, the impact of EGFR knockdown and ERK inhibitor treatment on angiogenesis was evaluated, with subsequent analysis of the expression of downstream angiogenic core molecules following these interventions. ResultsConfocal microscopy demonstrated the internalization of LoVo-Exos into HUVECs. In vitro angiogenesis assays further indicated that LoVo-Exos significantly enhanced the formation of tubular structures in HUVECs. Additionally, macroscopic examination of subcutaneous matrix plug formation in mice revealed a substantial increase in vascular-like structures within the matrix plugs following the administration of LoVo-Exos, compared to the PBS control group. Hematoxylin and eosin (HE) staining revealed the presence of erythrocyte-filled microvessels within the matrix plugs combined with LoVo-Exos. Furthermore, immunohistochemical analysis demonstrated the expression of the endothelial cell marker CD31 in these matrix plugs. The presence of CD31-positive cells in the LoVo-Exos-treated matrix plugs was associated with a significant enhancement in the formation of luminal structures. These findings suggest that LoVo-Exos facilitate the in vivo development of vascular-like structures. Subsequent investigations demonstrated that LoVo-Exos facilitated the delivery of pEGFR to HUVEC, thereby enhancing angiogenesis. Conversely, LoVo-Exos with EGFR knockdown exhibited a diminished capacity to promote angiogenesis, an effect that was further attenuated by the ERK phosphorylation inhibitor U0126. Western blot analysis assessing the activation of the EGFR-ERK signaling pathway in HUVEC indicated that LoVo-Exos augmented angiogenesis through the activation of this pathway. Furthermore, analysis of the impact of LoVo-Exos on the expression of downstream angiogenic core molecules revealed an increase in interleukin-8 (IL-8) secretion in HUVEC. The enhancement observed was diminished in LoVo-Exos following EGFR knockdown, and this reduction was counteracted by the ERK phosphorylation inhibitor U0126. ConclusionThe underlying mechanism may involve the delivery of pEGFR in LoVo-Exos to HUVECs, leading to increased IL-8 secretion via the EGFR-ERK signaling pathway, thereby enhancing the angiogenic potential of HUVECs. This finding may offer new insights into the mechanisms underlying cancer metastasis.

BACKGROUND:In recent studies,hydrogel loaded with exosomes has attracted wide attention as an emerging therapeutic strategy in the field of tissue engineering and regenerative medicine,and is considered as a promising means for the treatment of nerve regeneration and wound healing.OBJECTIVE:To review the application of hydrogel loaded with exosomes in nerve regeneration and wound healing and to provide reference and guidance for future research and clinical application.METHODS:The first author used a computer in May 2024 to retrieve the relevant literature published from January 2000 to May 2024 on PubMed and CNKI,searching for"exosome,hydrogel,nerve,nerve regeneration,wound,wound healing"in Chinese and English,eventually incorporating 66 papers for analysis.RESULTS AND CONCLUSION:(1)Hydrogel loaded with exosomes provides a promising path for nerve injury repair by exerting anti-inflammatory and anti-oxidation,stimulating axon growth and myelin regeneration.(2)Exosome-loaded hydrogel suppresses the level of inflammation and oxidative stress,accelerates the proliferation and migration of skin cells,collagen expression,and promotes blood vessel formation,significantly accelerates the wound healing process,and improves the healing quality.(3)The role of hydrogel loaded with exosomes in nerve regeneration and wound repair is still limited to cell and animal experiments,and does not involve clinical practice.In the future,more mechanistic studies,safety evaluation,and supplementary related clinical trials are still needed in the future.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the effect of ezetimibe combined with atorvastatin on the efficacy,blood lipids,ca-rotid ultrasound indicators in patients with coronary heart disease(CHD)and its safety.Methods:This randomized controlled study enrolled 98 CHD patients admitted to 945th Hospital of the PLA Joint Logistic Support Force be-tween June 2021 and June 2023.Patients were divided into intervention group and control group with 49 cases in each group.Patients in the control group was treated with atorvastatin-bascd routine medication comparing to those in intervention group receiving additional ezetimibe,both groups were treated for 90 d.Clinical efficacy,blood lipids,carotid ultrasound indicators,endothelial function indicators,and incidence of adverse reactions were compared between two groups.Results:Compared with patients in the control group,those in the intervention group had significant higher total effective rate(91.83％vs.73.47％,P=0.016).Compared with patients in the control group after treatment,those in intervention group had significant lower levels of low density lipoprotein cho-lesterol(LDL-C)[(2.74±0.61)mmol/L vs.(3.42±0.66)mmol/L],total cholesterol(TC)[(3.80±0.89)mmol/L vs.(4.69±1.02)mmol/L],triglyceride(TG)[(1.79±0.53)mmol/L vs.(2.35±0.62)mmol/L],re-sistance index(RI)[(52.02±6.32)％vs.(57.95±6.02)％],carotid intima-media thickness(IMT)[(0.91±0.17)mm vs.(1.08±0.24)mm],von Willebrand factor(vWF)[(19.03±3.76)mg/L vs.(23.41±4.42)mg/L],angiotensin Ⅱ(Ang Ⅱ)[(45.83±5.87)ng/L vs.(52.87±6.01)ng/L](P＜0.001 all);and significant high-er high density lipoprotein cholesterol(HDL-C)[(1.63±0.32)mmol/L vs.(1.35±0.27)mmol/L],peak systol-ic velocity(PSV)[(47.93±5.26)cm/s vs.(41.32±4.98)cm/s],end-diastolic velocity(EDV)[(36.14±5.10)cm/s vs.(30.73±4.48)cm/s],pulse index(PI)[(85.98±9.03)％vs.(78.42±8.82)％],vascular endothelial growth factor receptor 1(VEGFR1)[(289.14±32.98)ng/L vs.(258.34±29.32)ng/L](P＜0.001 all).There was no significant difference in the incidence of adverse reactions between the two groups(P=0.538).Conclusion:Ezetimibe combined with atorvastatin possesses significant therapeutic effect on CHD patients,which could signifi-cantly reduce blood lipids,improve the carotid blood flow velocity and vascular endothelial function with good safety.

BACKGROUND:In recent studies,hydrogel loaded with exosomes has attracted wide attention as an emerging therapeutic strategy in the field of tissue engineering and regenerative medicine,and is considered as a promising means for the treatment of nerve regeneration and wound healing.OBJECTIVE:To review the application of hydrogel loaded with exosomes in nerve regeneration and wound healing and to provide reference and guidance for future research and clinical application.METHODS:The first author used a computer in May 2024 to retrieve the relevant literature published from January 2000 to May 2024 on PubMed and CNKI,searching for"exosome,hydrogel,nerve,nerve regeneration,wound,wound healing"in Chinese and English,eventually incorporating 66 papers for analysis.RESULTS AND CONCLUSION:(1)Hydrogel loaded with exosomes provides a promising path for nerve injury repair by exerting anti-inflammatory and anti-oxidation,stimulating axon growth and myelin regeneration.(2)Exosome-loaded hydrogel suppresses the level of inflammation and oxidative stress,accelerates the proliferation and migration of skin cells,collagen expression,and promotes blood vessel formation,significantly accelerates the wound healing process,and improves the healing quality.(3)The role of hydrogel loaded with exosomes in nerve regeneration and wound repair is still limited to cell and animal experiments,and does not involve clinical practice.In the future,more mechanistic studies,safety evaluation,and supplementary related clinical trials are still needed in the future.

Objective:To investigate the prevalence of flight fatigue among helicopter flying personnel and analyze its contributors in order to provide data for related interventions.Methods:A cross-sectional study was conducted among 404 helicopter flying personnel between October 8, 2021 and July 31, 2022. Data was collected using a self-designed questionnaire, involving the demography of these subjects, sleep-related factors, flight fatigue, perceived causes of fatigue and coping strategies. The Pittsburgh Sleep Quality Index (PSQI), National Aeronautics and Space Administration Task Load Index (NASA-TLX) and Modified Fatigue Impact Scale (MFI-20) were used to assess sleep quality, mental workload, and levels of flight fatigue over the past month. The total scores of MFI-20 were compared across demographic groups, and correlations with PSQI and NASA-TLX scores were analyzed. Multiple linear regression was performed to identify the determinants of flight fatigue.Results:①Demography: among the 404 helicopter flying personnel, 92.8% (375/404) were pilots and 7.2% (29/404) navigators. As for years of service, 41.6% (168/404) served less than 5 years, while 58.4% (236/404) served more than 5 years. 37.9% (153/404) had a family history of insomnia. 18.8% (76/404) did not habitually nap, 68.9% (226/328) napped for ≤30 min, 31.1% (102/328) napped over 30 min, and 18.3% (74/404) had insomnia over the past month. As for helicopter flying personnel, 75.5% (305/404) reported experiencing fatigue, with 69.1% (279/404) attributing it to flight-related factors and 51.5% (208/404) using coffee as a countermeasure.②Scale scores: the total score of PSQI was [5 (3, 7)], while the highest daytime dysfunction score was [1(0, 2)]. The total score of NASA-TLX was [39.19 (26.57, 51.97)], and the effort score was the highest [10.31(5.07, 14.60)]. The total score of MFI-20 averaged (47.28±14.88), with the mental fatigue score being the highest [(10.03±4.42)]. ③Comparisons of MFI-20 total scores: flying personnel with ≤5 years of flying experience had higher MFI-20 total scores than those with >5 years, and those with a family history of insomnia had higher scores than those without ( t=3.35, 2.44, P=0.001, 0.015). Individuals with insomnia over the past month had higher scores than non-insomniacs ( t=3.33, P=0.001). Significant differences in MFI-20 scores were observed based on nap duration ( F=19.95, P<0.001). Non-nappers had higher scores than those napping for ≤30 min ( P=0.005). Flying personnel who napped for >30 min had higher scores than those did not ( P=0.043) or napped for ≤30 min ( P<0.001). ④Correlation analysis: the total score of MFI-20 was positively correlated with sleep quality, sleep latency, sleep disturbances, hypnotic medications, daytime dysfunction, and the total score of PSQI ( r=0.118-0.226, all P<0.05), but negatively with sleep duration ( r=-0.136, P=0.006). The total score of MFI-20 was positively correlated with mental demand, physical demand, and the total score of NASA-TLX ( r=0.119, 0.168, 0.184, P=0.017, 0.001, <0.001). ⑤Multiple linear regression analysis: the determinants of flight fatigue included aircraft types ( B=-4.956, 95% CI:-8.124--1.788), nap duration ( B=3.693, 95% CI: 1.267-6.119), sleep latency ( B=2.371, 95% CI: 0.229-4.513), sleep duration ( B=-7.383, 95% CI:-10.008--4.758), daytime dysfunction ( B=5.003, 95% CI: 2.967-7.039) and physical workload ( B=0.611, 95% CI: 0.324-0.898). Conclusions:Helicopter flying personnel are vulnerable to flight fatigue, which is strongly linked to sleep quality and mental workload. It is crucial to address flying personnel′s self-perceived fatigue, care about fatigue manifestations across aircraft types, and implement targeted interventions to improve sleep quality and reduce mental workload.

OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

Objective:To compare the effects of intermittent oro-esophageal tube feeding (IOE) and nasogastric tube feeding (NGT) on nutritional status, complications, swallowing function and airway protection in persons with post-stroke dysphagia (PSD).Methods:Sixty PSD patients were randomized into an observation group ( n=30) and a control group ( n=30). In addition to conventional medication and swallowing rehabilitation, the observation group received supplemental IOE nutrition, while the control group was given NGT. Before and after one month, both groups were evaluated using the Functional Oral Intake Scale (FOIS), and such nutritional indicators as body mass index (BMI), hemoglobin (Hb) levels, albumin (ALB), prealbumin (PAB), skinfold at the triceps (TSF) and arm muscle circumference (AMC) were measured. The morphology of each subject′s epiglottis, any edema of the arytenoid mucosa and vocal cord mobility were assessed using fiberoptic endoscopic evaluation of swallowing (FEES). Murray Secretion Scale ratings were documented, along with laryngeal sensation during swallowing, swallowing reflex, the Yale Pharyngeal Residue Severity Rating Scale, and the Rosenbek Penetration-aspiration Scale. Results:Both groups showed significant improvement in their average FOIS scores and all of the nutritional descriptors, but with significantly greater improvement in the observation group. Abnormalities in the shape of the epiglottis, arytenoid edema and vocal cord mobility had decreased significantly in both groups. This was also true of larynx sensation, swallowing reflex, pharyngeal secretions, residue and penetration/aspiration. On average the improvements were significantly greater in the observation group.Conclusion:Compared with NGT, IOE more effectively improves swallowing, enhances airway functioning and reduces NGT syndrome among PSD patients. These observations support its clinical adoption.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.