This study identified six novel azaphilones, isochromophilones G-L (1-6), and three novel biosynthetically related congeners (7-9) from Diaporthe sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (4) or linear conjugated polyenoid moieties (5 and 6), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW 264.7 macrophages at 20 μmol·L^-1. The novel compound (1) effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
Animals ; Mice ; RANK Ligand/genetics* ; RAW 264.7 Cells ; Osteoclasts/metabolism* ; Benzopyrans/isolation & purification* ; Osteogenesis/drug effects* ; Macrophages/metabolism* ; Molecular Structure ; Pigments, Biological/isolation & purification* ; Ascomycota/chemistry* ; NF-kappa B/genetics* ; Cell Differentiation/drug effects*

Objective To explore the accumulated effects of physical activity,sedentary behavior,and sleep on cardiorespiratory fitness(CRF)among college students and provide effective measures for enhancing their CRF. Methods From May to June in 2023,223 college students aged 18 to 24 years old were recruited from Tianjin University of Science and Technology for a 24 hours activity behavior survey and CRF testing.Compositional analysis was employed to investigate the relationships of physical activity,sedentary behavior,and sleep with CRF.Isotemporal substitution models were established to predict the effects of substituting various activity behaviors on CRF.Results The proportion of time spent on moderate-to-vigorous physical activity(MVPA)was positively correlated with CRF of college students(β=6.40,P=0.002),while the proportion of time spent on sedentary behavior was negatively correlated with CRF(β=-3.02,P=0.004).Light physical activity(LPA)and sleep were not correlated with CRF(β=-1.06,P=0.504).Isotemporal substitution results for 15-min increments showed that replacing other activity behaviors with MVPA significantly increased the CRF of college students[SB:1.72 mL/(kg·min),95% CI=0.94-2.51;LPA:1.82 mL/(kg·min),95% CI=0.95-2.68;sleep:1.64 mL/(kg·min),95% CI=0.84-2.45].In the dose-response relationship from -30 min to 30 min,reallocating time from other behaviors to MVPA had greater adverse effect on CRF than reallocating time from MVPA to other behaviors.Among all the substitutions,replacing LPA with MVPA had the most beneficial effect on improving CRF.Additionally,a 5-min increment was considered the optimal tipping point for MVPA replacing other activities.Conclusions This study underscores the importance of participating in MVPA for improving the CRF of college students.The isotemporal substitution model provides clear goals for the allocation of time for these behaviors,aiding in future intervention measure development and policy-making.
Humans ; Sedentary Behavior ; Sleep ; Students ; Cardiorespiratory Fitness ; Exercise ; Young Adult ; Adolescent ; Universities ; Male ; Female

ObjectiveTo investigate the effect of video-based educational intervention combined with maternal presence on perioperative adverse outcomes in preschool children undergoing general anesthesia， including cooperation in anesthesia induction， perioperative anxiety， pain and agitation during recovery. MethodsA total of 300 preschool children scheduled for general anesthesia in our hospital from June to December 2023 were randomly assigned to control group （n=150） and intervention group （n=150）. The control group received routine recovery care. For the intervention group， in addition to routine recovery care， a preoperative visit was scheduled one day before surgery. During this visit， mothers were guided to watch anesthesia videos with their children. During the waiting period in the operating room and 30 minutes after awakening， the mothers were guided to accompany the children for more than 30 minutes. Recovery conditions were recorded using the surgical anesthesia information system， and the children’s anesthetic induction compliance， perioperative anxiety， pain， and agitation were evaluated and recorded using the modified Yale Preoperative Anxiety Scale （m-YPAS）， the Induction Compliance Scale （ICC）， the Children’s Pain Behavior Scale （FLACC）， and the Pediatric Agitation and Emergence Delirium Scale （PAED）. ResultsOn the preoperative visit day， there were no statistically significant differences in baseline data between the two groups （P > 0.05）. For perioperative anxiety， the m-YPAS scores of the intervention group were significantly lower than those of the control group， both when entering the operating room waiting area （35.27±6.48 vs. 41.79±6.68， P < 0.05） and 30 minutes after postoperative recovery （20.13±7.05 vs. 35.75±9.51， P < 0.05）. In terms of anesthesia induction cooperation， the ICC scores of the intervention group were significantly lower than those of the control group （1.84±0.95 vs. 3.17±0.62， P < 0.05）， and the proportion of good induction cooperation was significantly higher than that of the control group （24.00% vs. 12.67%， P < 0.05）. There was no significant difference in awakening duration between the two groups， but the intervention group had a significantly shorter length of stay in the post-anesthesia care unit than the control group （0.90±0.29 hours vs. 1.29±0.42 hours， P < 0.001）. For perioperative agitation， the PAED scores of the intervention group were significantly lower than those of the control group （entering in the operating room waiting area： 8.5 vs. 9.2， P < 0.05； 30 minutes after postoperative recovery： 4.2 vs. 7.8， P < 0.05）. In terms of pain scores， the FLACC scores of the intervention group were also significantly lower than those of the control group， both when entering the operating room waiting area （ 5.3 vs. 6.7， P < 0.05； 30 minutes after postoperative recovery： 2.1 vs. 4.9， P < 0.05）. ConclusionsVideo-based educational intervention combined with maternal presence reduces the perioperative anxiety， pain and agitation of preschool children undergoing general anesthesia， and improved the compliance of anesthesia induction. It is recommended to promote this intervention measure in clinical practice.

Objective:To investigate the clinical efficacy of posterior midline incision combined with anteromedial approach in the treatment of complex olecranon fracture-dislocation.Methods:A retrospective analysis was performed on 26 patients (15 males and 11 females) with olecranon fracture-dislocation who were admitted from January 2020 to January 2024, including 5 cases of anterior transolecranon fracture-dislocation (2 cases of upper ulnar-radial joint dislocation), 21 cases of posterior transolecranon fracture-dislocation (5 cases of them were accompanied by upper ulnar-radial joint dislocation). Among them, there were 13 cases of traffic accidents, 7 cases of falling from heights, and 6 cases of walking falls. The average age is 45.1±15.3 years old (21-84 years old).Results:The operation time was 151.2±41.9 minutes, average tourniquet time was 93.7±22.6 minutes, and the intraoperative blood loss was 76.2±20.2 ml. The average follow-up was 16(12, 23) months, and the VAS score decreased significantly and the MEPS score increased significantly over time. At the last follow-up, the VAS score was 2(1, 2), and the MEPS score was 86.5±10.3, with 16 cases excellent, 7 cases good, and 3 cases medium, with an excellent rate of 89%. The range of motion of flexion-extension and pronation-supination were 119.3°±13.5°and 138.6°±15.2° respectively. Complications included 16 cases of ectopic ossification, of which 4 patients with significant effects on elbow function underwent surgical release 3-6 months after surgery. 1 case of ulnar nerve injury symptoms improved after emergency ulnar nerve release, and 1 case of elbow subluxation due to inaccurate coronoid process reduction and fixation. There were no serious complications such as vascular injury, internal fixation failure, fracture nonunion, and incision infection.Conclusion:The posterior midline incision combined with anteromedial approach can effectively treat complex olecranon fracture-dislocation and meet the requirements of early postoperative elbow rehabilitation.

Objective To explore the predictive value of growth differentiation factor 15(GDF-15)for atrial fibrillation(AF)in patients with coronary heart disease(CHD).Methods A prospective observation cohort of 1261 elderly CHD patients was randomly sampled from the First Medical Center of Chinese PLA General Hospital from January 2012 to December 2015.ELISA was used to detect GDF-15 level in all the subjects,and their baseline data were collected.Until March 2023,93 patients were lost during the follow-up period,and finally 1168 patients completed the follow-up,with a median time of 9.4 years.According to AF occurred or not during the period,the eligible patients were divided into an AF group(197 cases)and a non-AF group(971 cases),and based on their medical history,also assigned into a stable angina pectoris(SAP,n=304)and an acute coronary syndrome group(ACS,n=864).Logistic regression analysis was used to determine whether GDF-15 is a risk factor for AF in elderly CHD patients.ROC curve was plotted to assess the predictive value of GDF-15,guideline recommended CHARGE-AF scoring model,and their combination for AF events in the patients.Results The AF group had significantly advanced age,larger proportions of smoking history,type 2 diabetes,hypertension,old myocardial infarction,stroke,ACS and administration of statins,higher ratio of angiotensin converting enzyme inhibi-tor/angiotensin receptor blocker,and elevated levels of GDF-15 and N-terminal pro-B-type natri-uretic peptide,and lower left ventricular ejection fraction,SAP incidence,and low-density lipopro-tein cholesterol,total cholesterol and triglycerides levels when compared with the non-AF group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that GDF-15 was not a risk factor for AF in elderly CHD patients(OR=0.92,95％CI:0.74-1.16,P=0.489),but was a risk factor for AF in SAP patients(OR=1.38,95％CI:1.07-2.79,P=0.015),and in ACS patients,still not a risk factor for AF(OR=0.81,95％CI:0.63-1.05,P=0.814).ROC curve analysis showed that the AUC value of GDF-15 combined with the CHARGE-AF scoring model in predic-ting AF was 0.682 in the elderly CHD patients,0.746 in the SAP patients,and 0.680 in the ACS patients.Conclusion Elevated GDF-15 level is an independent risk factor and predictor of AF in elderly SAP patients.In SAP patients,the combination of GDF-15 and CHARGE-AF scoring model further improves the predictive performance of AF occurrence.

Objective:To investigate whether intermittent fasting alleviates insulin resistance in a polycystic ovary syndrome(PCOS) mouse model through the regulation of autophagy.Methods:Fifty 3-week-old female C57BL/6J mice were randomly assigned into the following groups using a random number table: normal control(NC) group( n=10), maintained on a standard chow diet; high-fat diet(HFD) group( n=10) fed a diet with 60% of calories derived from fat; and PCOS model group( n=30), established by combining a HFD with dehydroepiandrosterone(DHEA) administration. Successful modeling was confirmed by disrupted estrous cycles, hyperandrogenism, and polycystic ovarian morphology. The PCOS model mice were further divided into three groups: PCOS group( n=9), PCOS with intermittent fasting group(PCOS+ IF, n=9), and PCOS with intermittent fasting plus the autophagy inhibitor 3-methyladenine(3-MA) group(PCOS+ IF+ 3-MA, n=9). Autophagy levels were assessed by detecting markers LC3 and p62 and observing autophagosomes via transmission electron microscopy. Glucose tolerance test(GTT) and insulin tolerance test(ITT) were performed, and the area under the curve(AUC) was calculated to evaluate insulin resistance. Western blotting was used to detect phosphorylation levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin(mTOR), and p70S6 kiase(p70S6K). Results:Compared with the NC group, the PCOS model group showed absent estrous cycles, significantly elevated serum testosterone, sex hormone binding globulin, and luteinizing hormone(LH) levels( P<0.001), and polycystic ovarian changes on hematoxylin-eosin staining, confirming successful model establishment. Immunohistochemistry, transmission electron microscopy, and Western blotting demonstrated that autophagy levels were increased in the PCOS+ IF group compared with the PCOS group, while 3-MA administration reduced the intermittent fasting - induced autophagy. The AUC values for both GTT and ITT were significantly lower in the PCOS+ IF group than those in the PCOS group( P<0.001, P=0.003), but increased in the PCOS+ IF+ 3-MA group compared to the PCOS+ IF group( P<0.001, P=0.020). Western blotting analysis showed that phosphorylation levels of PI3K, Akt, mTOR, and p70S6K were significantly decreased in the PCOS+ IF group compared with the PCOS group( P=0.002, P=0.001, P=0.001, and P<0.001, respectively), and increased in the PCOS+ IF+ 3-MA group compared with the PCOS+ IF group( P=0.021, P=0.041, P=0.047, and P=0.024, respectively). Conclusions:Intermittent fasting alleviates insulin resistance in a PCOS mouse model through inhibitiing PI3K/Akt/mTOR signaling pathway and promoting autophagy.

Objective:To investigate the influence of the complexity metrics of the multi-leaf collimator (MLC) on the γ-pass rate of volumetric modulated arc therapy (VMAT) plans for nasopharyngeal carcinoma (NPC).Methods:A total of 60 VMAT plans for NPC were selected to measure the γ-pass rate. The MLC data across all control points (CPs) in each VMAT plan were analyzed to calculate the mean field area (MFA), average leaf gap (ALG), small aperture score (SAS), and their corresponding weighted metrics including MFAW, ALGW, and SASW, considering dose weight (W). Pearson′s bivariate correlation analysis was conducted to examine the correlations between MLC complexity metrics and the γ-pass rate. Moreover, the receiver operating characteristic (ROC) analysis was employed to assess the predictive efficacy of MLC complexity metrics on dose verification result.Results:Under the 3%/3 mm, 3%/2 mm, and 2%/2 mm criteria, the MFA in the 60 VMAT plans exhibited a positive correlation with the γ-pass rate ( r=0.82, 0.79, 0.72, P<0.05), and the MFAW was also positively correlated with the γ-pass rate ( r=0.83, 0.81, 0.75, P<0.05). The ALG manifested a positive correlation with the γ-pass rate ( r=0.82, 0.79, 0.74, P<0.05), as did the ALGW ( r=0.83, 0.81, 0.77, P<0.05). The SAS(0-1 cm), SAS(1-2 cm), SAS(2-3 cm), and SAS(3-4 cm) displayed negative correlations with the γ-pass rate ( r= -0.86, -0.82, -0.71, -0.84, -0.82, -0.72, -0.79, -0.79, -0.73, -0.30, -0.35, -0.42, P<0.05), whereas the SAS(4-5 cm), SAS(5-6 cm), and SAS(6-40 cm) showed positive correlations with the γ-pass rate ( r=0.49, 0.45, 0.33, 0.73, 0.71, 0.59, 0.79, 0.79, 0.76, P<0.05). The outcomes of SASW reveal slightly stronger correlations than those of SAS. In terms of correlations among complexity metrics, a positive correlation was observed between MFA and ALG ( r=0.98, P<0.05). ALG was negatively correlated with SAS(0-1 cm), SAS(1-2 cm), SAS(2-3 cm), and SAS(3-4 cm) ( r= -0.95, -0.94, -0.89, -0.39, P<0.05), and positively correlated with SAS(4-5 cm), SAS(5-6 cm), and SAS(6-40 cm) ( r=0.51, 0.77, 0.92, P<0.05). The weighted result mirrored these correlations. The ROC-derived analytical result indicate that MFA, MFAW, ALG, ALGW, SAS(0-1 cm), SAS(1-2 cm), SAS(2-3 cm), SAS(6-40 cm), SASW(0-1 cm), SASW(1-2 cm), SASW(2-3 cm), and SASW(6-40 cm) demonstrated exceptional predictive efficacy for dose verification result [Area under the curve (AUC) > 0.9, P<0.05]. Conclusions:The γ-pass rate of VMAT plans for NPC is strongly correlated with MLC complexity metrics, which demonstrate excellent predictive efficacy for dose verification result. The increased uncertainty in dose calculations and measurements caused by narrow fields generated by the MLC is a significant factor contributing to the reduced γ-pass rate of VMAT plans. This finding is associated with discrepancies in the precision of treatment planning system (TPS) modeling and the accuracy of dose verification tools, providing a reference for similar challenges.

Objective:To investigate the differences in dosimetric parameters for target volumes and organs at risk (OARs), radiation doses to reconstructed tissues, and beam-on time in radiotherapy among helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and fixed-field intensity-modulated radiotherapy (F_IMRT) following immediate breast reconstruction for breast cancer, thereby providing a reference for the selection of clinical radiotherapy techniques.Methods:This study retrospectively investigated 15 breast cancer patients who underwent radiotherapy following modified radical mastectomy and immediate breast reconstruction at the Liuzhou Worker′s Hospital from August 2018 to July 2023. During target volume delineation, precautions were taken to avoid the reconstructed tissues, which were delineated separately. Customized HT, VMAT, and F_IMRT treatment plans were designed for each patient. The plans were categorized into the HT, VMAT, and F_IMRT groups based on different radiotherapy techniques employed. They were comparatively analyzed through one-way analysis of variance (ANOVA), with multiple comparisons further conducted in the case of significant differences.Results:Statistical analyses reveal significant differences in various parameters of target volumes among the three groups of plans ( F = 38.73, 14.95, 37.01, 48.05, 35.55, 22.56, 34.30, P < 0.05). Pairwise comparisons indicate that the maximum dose ( D2%), minimum dose ( D98%), mean dose ( Dmean), and the proportion of high-dose volumes within the target volume ( V107%and V110%) in both the HT and VMAT groups were significantly better than those in the F_IMRT group. The HT group demonstrated the optimal conformity index (CI), while the VMAT group displayed the superior homogeneity index (HI) compared to the other two groups. In terms of OAR, the V20 of the ipsilateral lung was the lowest in the HT group ( F = 14.31, P < 0.05) and the highest in the F_IMRT group ( F = 14.31, P < 0.05). However, the V5 and Dmean for both the ipsilateral and contralateral lungs in the HT group significantly surpassed those of the other groups ( F = 39.16, 31.91, P < 0.05). The mean dose Dmean ( F = 5.57, P < 0.05) of the contralateral breast was significantly reduced in the VMAT group compared to the other two groups. No statistically significant differences were observed for other OARs, including the heart, spinal cord PRV, thyroid, and humeral head ( P > 0.05). The radiation doses to reconstructed tissues ( Dmax, V53.5, Dmean) ascended in the order of HT, VMAT, and F_IMRT groups ( F = 17.69, 17.53, 15.11, P < 0.05). The HT and F_IMRT groups showed similar beam-on times ( P > 0.05), both exceeding that of the VMAT group by several folds ( F = 28.72, P < 0.05). Conclusions:The comparative analysis indicates that the three radiotherapy techniques exhibit distinct advantages and limitations, with F_IMRT demonstrating the least comprehensive advantage. HT can enhance the conformity of target volumes while reducing the overall radiation doses to reconstructed tissues and the crucial indicator V20 in the ipsilateral lung. VMAT demonstrates the highest treatment efficiency, yielding improved dose uniformity in the target volume and reduced radiation doses to the contralateral breast. It is advisable to prioritize HT or VMAT based on actual clinical conditions.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To study the impact of third-party disability in caregivers of aphasia patients with stroke based on the concept of the International Classification of Functioning, Disability and Health (ICF), and to examine the factors influencing it.Methods:Sixty-four pairs of stroke patients with aphasia and their caregivers were recruited. The patients were assessed using a general information questionnaire and the western aphasia battery (WAB), while the caregivers were surveyed using a general information questionnaire and a family aphasia measure of life impact (FAMLI) developed based on the ICF framework. Pearson correlation analysis was performed on the WAB scores of the patients and the FAMLI scores of their caregivers, and multiple linear regression analysis was used to screen out the factors significantly influencing third-party disability among the caregivers.Results:The caregivers′ average total FAMLI score was (33.64±19.38), with significant differences reflecting the patient′s age and the course of the disease. Correlation analysis showed that the patients′ cerebral cortical quotients (CQs) and aphasia quotients were significantly and positively correlated with the FAMLI scores of their caregivers ( r-values of 0.408 and 0.395, respectively). Multiple linear regression analysis showed that a patient′s CQ score and age were significantly correlated with the FAMLI score of their caregiver (β-values of 0.326 and 0.599, respectively). Conclusion:The caregivers of stroke survivors with aphasia tend to have third-party disabilities. The patient′s age and the severity of their aphasia are important predictors of life quality for their caregivers.