BACKGROUND:During healing process of chronic wounds,excessive production of reactive oxygen species can impair the function of L929 fibroblasts,thereby delaying wound repair.Therefore,protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE:To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma(CMC-OCS/PRP)hydrogel on L929 cells under H2O2 stimulation. METHODS:CMC-OCS/PRP hydrogels were prepared,and the micromorphology,degradation performance,scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized.L929 cells with good growth state were taken and cultured in five groups.The control group was cultured conventionally.H2O2 was added to the H2O2 group.Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract+H2O2 was added to the CMC-OCS group.Platelet-rich plasma gel extract+H2O2 was added to the PRP group.The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract+H2O2.Each group was treated with hydrogel extract for 6 hours,and then H2O2 for 24 hours.After culture,the levels of active oxygen and malondialdehyde,apoptosis and expression of collagen fiber I protein were detected.In the presence of H2O2,the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours,respectively.Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION:(1)CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability,could effectively remove H2O2 and hydroxyl radicals in vitro,and had good biocompatibility.(2)Compared with the control group,the apoptosis rate,reactive oxygen species,and malondialdehyde levels were increased(P<0.05);the spread area of cells was decreased(P<0.05),and the expression of collagen fiber I protein had no significant changes(P>0.05)in the H2O2 group.Compared with the H2O2 group,reactive oxygen species level was decreased in the CMC-OCS group(P<0.05),malondialdehyde level was decreased(P<0.05),and cell spread area was increased(P<0.05)in the PRP group,CMC-OCS group,and CMC-OCS/PRP group;apoptosis rate was decreased in the CMC-OCS/PRP group(P<0.05),and collagen fiber I protein expression was increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05).(3)Compared with the control group,the number of cell migration was decreased(P<0.05),and the migration area had no significant change(P>0.05)in the H2O2 group.Compared with the H2O2 group,the number and area of cell migration were increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05),and the increase was most significant in the CMC-OCS/PRP group.(4)Under oxidative stress,CMC-OCS/PRP hydrogel can improve the migration ability of fibroblasts,resist cell apoptosis,and preserve cell extension function.

BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

OBJECTIVE: To observe the effect of acupuncture at back-shu points on patients with post-stroke tracheotomy on the basis of extracorporeal diaphragmatic pacing (EDP) combined with conventional acupuncture. METHODS: A total of 64 patients with post-stroke tracheotomy were randomly divided into an experiment group (32 cases, 2 cases dropped out) and a control group (32 cases, 2 cases dropped out). The control group received EDP combined with conventional acupuncture, acupuncture was applied at Baihui (GV20), Zhongwan (CV12) and bilateral Fengchi (GB20), Quchi (LI11), Hegu (LI4), Neiguan (PC6), Xuehai (SP10) , Yinlingquan (SP9), Sanyinjiao (SP6), Zusanli (ST36), 30 min each time. The experiment group was treated with acupuncture at bilateral Feishu (BL13), Pishu (BL20), Shenshu (BL23) on the basis of the treatment in the control group, 30 min each time. Acupuncture in both groups was given once a day, 5 days a week for 4 weeks. Before and after treatment, the pulmonary function (forced vital capacity [FVC], first second forced expiratory volume [FEV₁], peak expiratory flow [PEF], maximal inspiratory pressure [MIP], maximal expiratory pressure [MEP]), diaphragmatic thickening fraction (DTF), diaphragm excursion (DE), postural assessment scale for stroke patients (PASS) score and Berg balance scale (BBS) score were observed in the two groups. The extubation success rate was recorded in the two groups. RESULTS: After treatment, the FVC, FEV₁, PEF, MIP and MEP in the two groups were increased compared with those before treatment (P<0.001), and above indexes in the experiment group were higher than those in the control group (P<0.001, P<0.01). After treatment, the DTF and DE in the two groups were increased compared with those before treatment (P<0.001), the DE in the experiment group was higher than that in the control group (P<0.001). After treatment, the PASS and BBS scores in the two groups were increased compared with those before treatment (P<0.001), and the BBS score in the experiment group was higher than that in the control group (P<0.001). The extubation success rate of the experiment group was 73.3% (22/30), which was higher than 46.7% (14/30) in the control group (P<0.05). CONCLUSION On the basis of EDP combined with conventional acupuncture, acupuncture at back-shu points can improve the pulmonary function, respiratory muscle strength, trunk control and balance abilities in patients with post-stroke tracheotomy, and increase the extubation success rate.
Humans ; Acupuncture Therapy ; Male ; Female ; Middle Aged ; Aged ; Stroke/complications* ; Acupuncture Points ; Tracheotomy ; Adult ; Airway Extubation ; Treatment Outcome

Objective:To investigate the incidence of basal ganglia calcification (BGC), and risk factors for BGC in acute ischemic stroke (AIS) patients.Methods:A total of 730 patients with nervous system diseases hospitalized in Department of Neurology, Shanghai Punan Hospital of Pudong New Area from January 2023 to December 2023 were enrolled. These patients were divided into AIS group ( n=380) and non-AIS group ( n=350). Propensity score matching (PSM) was firstly used for 1:1 matching to eliminate the differences in baseline data of these patients; BGC incidence was compared between the two groups. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for BGC in AIS patients. Results:After PSM, there were 251 patients in the AIS group and 251 patients in the non-AIS group. No significant difference was noted between the two groups in age, gender, histories of hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking and drinking, ratio of previous stroke, and serum calcium, low-density lipoprotein cholesterol, homocysteine, uric acid, estimated glomerular filtration rate, or parathyroid hormone ( P>0.05). BGC incidence in the AIS group was 33.1% (83/251), with mild BGC in 55 patients (21.9%), moderate BGC in 19 patients (7.6%), and severe BGC in 9 patients (3.6%). BGC incidence in the AIS group was significantly higher than that in the non-AIS group (33.1% vs. 16.7%, P<0.05). Univariate and multivariate Logistic regression analyses showed that female ( OR=1.842, 95% CI: 1.021-3.324, P=0.043) and diabetes ( OR=1.953, 95% CI: 1.205-3.167, P=0.007) were independent risk factors for BGC in AIS patients. Conclusion:Compared with non-AIS patients, AIS patients trend to have BGC; female AIS patients with diabetes mellitus are more likely to have BGC.

Bone defect repair is an urgent problem in the field of orthopedics,and numerous researchers are working to develop more effective treatment plans.The accurate evaluation of bone repair after surgery is a crucial step.In line with the development of computed tomography(CT)imaging,dual-energy CT imaging has shown significant advantages in analyzing bone composition and reducing metal artifacts.This article reviews the application of dual-energy CT imaging for the evaluation of bone repair in animals.

Palliative care is a way to help end-of-life populations improve their quality of life， and its development in practice cannot be separated from the level of education in palliative care. At present， some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system， lack of medical students’ hospice knowledge； insufficient interdisciplinary teaching faculty， weak palliative care awareness of medical students； single teaching evaluation mode； weak palliative care practice teaching links. To this end， it is necessary to improve the palliative care curriculum system， explore rich and diverse teaching methods； strengthen interdisciplinary teaching and faculty development， enhancing the awareness of palliative care among medical students；establish a scientific and effective evaluation method， carry out multi-dimensional dynamic assessment； expand the palliative care practice teaching base， and accurately improve the practical skills of medical students in palliative care， and other countermeasures to improve the level of palliative care education， and to help the strategy of Healthy China.

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

This study aimed to elucidate the mechanism of action of metformin (MET) in inhibiting the malignant progression of hepatocellular carcinoma (HCC) by regulating the degradation of aldo-keto reductase family 1 member C3 (AKR1C3). The correlation between the sensitivity of different hepatocellular carcinoma cell lines to MET and their basal expression levels of AKR1C3 was firstly evaluated. MET was found to significantly reduce the level and accelerate the degradation rate of AKR1C3 protein by Western blot. The interaction between MET and AKR1C3 protein was confirmed by cellular thermal shift assay (CETSA). Proteasome inhibitor MG132 and the lysosomal inhibitor chloroquine (CQ) were used to screen the degradation pathway, and confirm, in combination with the HBSS starvation-induced autophagy model, that MET mediated the degradation of AKR1C3 through the autophagy lysosome pathway. Ubiquitylation assay showed that MET specifically enhanced the K63-linked polyubiquitylation modification of AKR1C3. Sequestosome 1 (SQSTM1/p62) knockdown, immunoprecipitation, and immunofluorescence co-localization analyses confirmed that the autophagy receptor p62 plays a key role in mediating MET-induced degradation of AKR1C3. The adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor compound C was used to demonstrate that the regulatory effect of MET on AKR1C3 is independent of the classical AMPK signaling pathway. The experimental results showed that metformin promoted the ubiquitination modification of AKR1C3 by targeting AKR1C3, enhanced the binding of AKR1C3 to autophagy receptor p62, then degraded the AKR1C3 protein through selective autophagy-like pathway, and ultimately inhibited the malignant phenotypes of hepatocellular carcinoma cells, which is a regulatory mechanism free of the classical AMPK activation pathway of metformin.

Objective To analyze the relationship between hypertension combined with obstructive sleep apnea hypopnea syndrome(OSAHS)and intima-media thickness(IMT)and explore the correlation between the risk of IMT and hypertension with OSAHS patients.Methods Select 50 patients with hypertension and OSAHS patients who were treated in Jiaxing Hospital of Traditional Chinese Medicine during January 2020 to February 2024 as observation group,while 50 patients with simple hypertension were used as control groups to collect two groups of patients'sleep respiratory monitoring disorders(AHI),lowest blood oxygen saturation(L-SaO2)at night,average hemodium oxygen saturation(M-SaO2)at night,dynamic blood pressure 24h,daytime and night's average diastolic blood pressure,IMT,conducting relevant statistical analysis,compares correlation between IMT of two groups and the severity of OSAHS.Results Compared with control group,observation group AHI,IMT,average systolic blood pressure voltage and average diastolic blood pressure increased significantly(P＜0.01),L-SaO2,M-SaO2 decreased significantly(P＜0.01).Observation group AHI and average systolic blood voltage and average diastolic pressure of average systolic blood pressure at 24h,daytime,and night were positively correlated(P＜0.01),L-SaO2,24h and daytime average contraction pressure were negatively correlated(P＜0.05).Observation group AHI and IMT were positive,and L-SaO2,M-SaO2 and IMT were negatively related(P＜0.01).Conclusion Severity of the disease of hypertension combined with OSAHS patients is closely related to patient's blood pressure level and change of IMT.Actively controlling blood pressure and IMT may help improve prognosis of patients,reduce the occurrence of cardiovascular events.The prognostic evaluation has certain clinical value.