Objective To examine the anti-central-fatigue function of maca and its underlying mechanism.Methods Forty Sprague-Dawley rats were divided randomly into a negative control group,model control group,and low-,medium-,and high-dose maca groups(0.6,1.2,and 2.4 g/kg·body weight).Rats in all groups except the negative control group were subjected to multi-factor stimulation,including cold-water swimming,sleep deprivation,restraining,and tail-clamping,to establish central fatigue rat models.Rats in the low-,medium-,and high-dose maca groups received 0.6,1.2,or 2.4 g/kg maca,respectively,by gavage for 35 days.Behavioral testing was carried out using the Morris water-maze,sucrose-preference,and tail-suspension tests.Markers of oxidative stress in the hippocampus,including superoxide dismutase(SOD),malondialdehyde(MDA),and catalase(CAT),were detected using test kits.Proteins connected with the AMP-activated protein kinase(AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α)signaling pathway in the hippocampus were detected by Western blot.Results Rats in the low-,medium-,and high-dose maca groups spent significantly more time in the target quadrant compared with the model control group(P＜0.05 or P＜0.01),but there was no significant dose-effect relationship.Rats in the medium-and high-dose maca groups showed decreased escape latency(P＜0.05),increased time crossing the platform location(P＜0.05),increased sucrose preference(P＜0.05),decreased tail suspension time(P＜0.05),increased the activities of CAT(P＜0.01)and SOD(P＜0.05),and decreased MDA content(P＜0.01).Rats in the low-,medium-,and high-dose maca groups also showed significantly increased protein expression levels of AMPK and nuclear respiratory factor 1(P＜0.01 or P＜0.05),but no significant dose-effect relationship was observed.Rats in the medium-and high-dose maca groups showed increased protein expression of PGC-1α(P＜0.05 or P＜0.01),and rats in the high-dose maca group showed increased protein expression of SIRT1 and mitochondrial transcription factor A(P＜0.05 or P＜0.01).Conclusions Maca can improve the indicators of central fatigue in rats,determined by behavioral testing and oxidative stress-related factors.The underlying mechanism may be related to its regulatory effects on the AMPK/SIRT1/PGC-1α signaling pathway.

Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar^-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Animals ; Osteoclasts/cytology* ; Periodontitis/metabolism* ; Cell Differentiation ; Mice ; Fibroblasts/metabolism* ; Macrophages ; Disease Models, Animal ; Complement C3/metabolism* ; Humans ; Disease Progression ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective The high global prevalence of adenovirus serotype 5(Ad5)infection,particularly in developing coun-tries,has led to widespread pre-existing neutralizing antibodies(NAbs)against this serotype.These NAbs may substantially im-pair the efficacy of Ad5-based therapeutics,necessitating the development of novel strategies to circumvent neutralizing antibody interference.Methods A novel Ad5-based vector was engineered via homologous recombination,wherein the hexon hypervari-able region(HVR)1,2,and 5 of Ad5 were strategically replaced with their counterparts from the less prevalent adenovirus sero-type 35(Ad35).This chimeric design aimed to reduce vector neutralization by Ad5-specific NAbs while preserving infectivi-ty.Results The hexon HVR-modified Ad5 vector exhibited reduced neutralization by pre-existing Ad5 antibodies while retai-ning efficient infectivity in tumor cells.In animal models,thesemodified vectors demonstrated excellent oncolyticability and still maintained strong tumor-killing activity in nude mice that received passive immunization with Ad5 neutralizing antibody ser-um.Conclusion The hexon HVR-modified Ad5 vectors demonstrate effective tumor infection rates and oncolytic efficacy in the presence of pre-existing Ad5 NAbs,suggesting promising clinical potential.

Objective To examine the anti-central-fatigue function of maca and its underlying mechanism.Methods Forty Sprague-Dawley rats were divided randomly into a negative control group,model control group,and low-,medium-,and high-dose maca groups(0.6,1.2,and 2.4 g/kg·body weight).Rats in all groups except the negative control group were subjected to multi-factor stimulation,including cold-water swimming,sleep deprivation,restraining,and tail-clamping,to establish central fatigue rat models.Rats in the low-,medium-,and high-dose maca groups received 0.6,1.2,or 2.4 g/kg maca,respectively,by gavage for 35 days.Behavioral testing was carried out using the Morris water-maze,sucrose-preference,and tail-suspension tests.Markers of oxidative stress in the hippocampus,including superoxide dismutase(SOD),malondialdehyde(MDA),and catalase(CAT),were detected using test kits.Proteins connected with the AMP-activated protein kinase(AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α)signaling pathway in the hippocampus were detected by Western blot.Results Rats in the low-,medium-,and high-dose maca groups spent significantly more time in the target quadrant compared with the model control group(P＜0.05 or P＜0.01),but there was no significant dose-effect relationship.Rats in the medium-and high-dose maca groups showed decreased escape latency(P＜0.05),increased time crossing the platform location(P＜0.05),increased sucrose preference(P＜0.05),decreased tail suspension time(P＜0.05),increased the activities of CAT(P＜0.01)and SOD(P＜0.05),and decreased MDA content(P＜0.01).Rats in the low-,medium-,and high-dose maca groups also showed significantly increased protein expression levels of AMPK and nuclear respiratory factor 1(P＜0.01 or P＜0.05),but no significant dose-effect relationship was observed.Rats in the medium-and high-dose maca groups showed increased protein expression of PGC-1α(P＜0.05 or P＜0.01),and rats in the high-dose maca group showed increased protein expression of SIRT1 and mitochondrial transcription factor A(P＜0.05 or P＜0.01).Conclusions Maca can improve the indicators of central fatigue in rats,determined by behavioral testing and oxidative stress-related factors.The underlying mechanism may be related to its regulatory effects on the AMPK/SIRT1/PGC-1α signaling pathway.

Objective The high global prevalence of adenovirus serotype 5(Ad5)infection,particularly in developing coun-tries,has led to widespread pre-existing neutralizing antibodies(NAbs)against this serotype.These NAbs may substantially im-pair the efficacy of Ad5-based therapeutics,necessitating the development of novel strategies to circumvent neutralizing antibody interference.Methods A novel Ad5-based vector was engineered via homologous recombination,wherein the hexon hypervari-able region(HVR)1,2,and 5 of Ad5 were strategically replaced with their counterparts from the less prevalent adenovirus sero-type 35(Ad35).This chimeric design aimed to reduce vector neutralization by Ad5-specific NAbs while preserving infectivi-ty.Results The hexon HVR-modified Ad5 vector exhibited reduced neutralization by pre-existing Ad5 antibodies while retai-ning efficient infectivity in tumor cells.In animal models,thesemodified vectors demonstrated excellent oncolyticability and still maintained strong tumor-killing activity in nude mice that received passive immunization with Ad5 neutralizing antibody ser-um.Conclusion The hexon HVR-modified Ad5 vectors demonstrate effective tumor infection rates and oncolytic efficacy in the presence of pre-existing Ad5 NAbs,suggesting promising clinical potential.

Objective:To investigate the effect of oral immunotherapy with donor human milk on feeding tolerance in premature infants with very low birth weight.Methods:A total of 94 extremely low birth weight preterm infants admitted to the neonatal Intensive Care Unit of Cangzhou People's Hospital from August 2022 to February 2024 were selected, These infants were randomized at 1:1 into 2 groups (47 cases each) using random number method. The control group were given oral 0.9% sodium chloride (oral drip), while the experimental group were given donor human milk (oral drip). General information were collected, including gender, delivery method, twins or not, small for gestational age or not, birth weight, gestational age, intestinal feeding of dairy products, and so on. Total intestinal feeding time, length of hospital stay and feeding intolerance were compared between groups.Results:The total intestinal feeding time and length of hospital stay were significantly shorter in the experimental group compared with the control group ( P<0.05). The incidence of feeding intolerance in the experimental group was also lower than that in the control group ( P<0.05). Conclusion:Oral immunotherapy with donor human milk can improve the feeding tolerance in premature infants with very low birth weight and shorten the hospital stay.

Objective:To explore the relationship between the imaging features of enhanced MRI in patients with central chronic pulmonary artery thromboembolism (CPTE) and pulmonary vascular resistance (PVR).Methods:Thirty-nine patients with CPTE who had contrast-enhanced MRI examination were retrospectively enrolled this study from January 2018 to December 2020. And 33 patients who received right heart catheterization were divided into two groups based on PVR=1 000 dyn·s·cm -5. The differences of imaging features of CPTE in enhanced MRI between the two groups were compared. The relationship between gender, duration of disease, age, pleural thickening, bilateral bronchial artery dilation, number of the involved vascular segments, number of thrombosis, number of the thrombus-related delayed enhancement of artery wall and PVR was analyzed by binary logistic regression. Results:In 39 patients with central CPTE, the dilated lumen (168, 43.30%) and delayed enhancement of wall (122, 31.52%) were found in most of pulmonary arteries. The rate of the lumen dilatation associated with thrombus was the highest among that of the lumen abnormality (66, 52.80%). There were more thrombi in PVR<1 000 dyn·s·cm -5 group than those in PVR≥1 000 dyn·s·cm -5 group (χ 2=9.55, P=0.002). There was no significant difference in the incidence of wall delayed enhancement associated the thrombus between the two groups (χ 2=0.90, P=0.344). The incidence of bilateral bronchial arterial dilatation in PVR<1 000 dyn·s·cm -5 group was higher than that in PVR≥1 000 dyn·s·cm -5 group ( P=0.019). Logistic regression analysis showed that female, the less number of involved vascular segments and bilateral bronchial artery dilation were correlated with the lower PVR. Conclusions:Enhanced MRI is helpful to accurately evaluate the lumen abnormality of pulmonary artery and wall remodeling in central CPTE, which is of great value for the assessment of patients′ conditions and treatment effect.

Objective:To analyze the late gadolinium enhancement (LGE) manifestations, cardiac function, and myocardial strain by feature tracking (FT) in Takayasu arteritis (TA) with pulmonary artery involvement (PTA) using cardiac MR (CMR), and then to investigate manifestations of the impaired myocardial structure and function.Methods:A retrospective study was performed on 32 patients with PTA and 21 healthy subjects without cardiopulmonary diseases from January 2017 to December 2020. All of them underwent CMR examinations. According to the presence of pulmonary arterial hypertension (PAH),PTA patients were divided into two groups including PAH group (11 cases) and non-PAH group (21 cases). LGE manifestations were observed and Fisher exact test was used for statistical analysis between the two groups. Cardiac function parameters and FT values including global peak strain of the left and right ventricle were calculated separately in PAH, non-PAH group of patients and healthy controls, using One-way ANOVA or non-parametric Kruskal-Wallis test for statistical analysis including a pairwise comparison between groups. The correlations between FT values of the PAH group and parameters measured by right heart catheterization test (RHC) and transthoracic echocardiography were analyzed using Pearson or Spearman correlation analysis.Results:There were 23 PTA patients (71.9%) with LGE. LGE in the interventricular insertion points (IPs)(11/11), and in the mid-wall (11/11) or epicardial (10/11) myocardium was more common ( P values were 0.006,<0.001 and 0.011, respectively) in PAH group, compared with LGE in the IPs (11/21), and in the mid-wall (7/21) or epicardial (9/21) myocardium in non-PAH group. The absolute values of left ventricular global peak circumferential strain (LVGPCS), left ventricular global peak longitudinal strain (LVGPLS) and right ventricular global peak longitudinal strain in PAH group were smaller than those in healthy subjects ( P<0.05). The absolute values of LVGPCS and LVGPLS in non-PAH group were smaller than those in healthy subjects ( P<0.05). In PAH group, mean pulmonary artery pressure of RHC was correlated with several FT parameters ( P<0.05), especially left ventricular global peak radial strain ( r=-0.807, P=0.009) and LVGPCS ( r s=0.817, P=0.007). Conclusions:Myocardial injury can be seen in PTA patients. And LGE in the IPs and LGE in the mid-wall or epicardial myocardium is more common in PTA patients with PAH. LVGPCS and LVGPLS can early indicate left heart dysfunction in PTA patients without PAH.