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 systematic analyze the risk factors for new-onset urethral stricture after transurethral holmium laser enucleation of the prostate(HoLEP)in the treatment of benign prostatic hyperplasia(BPH).Methods A case-control study was conducted on 746 BPH patients undergoing HoLEP treatment in Department of Urology of the Third Medical Center of Chinese PLA General Hospital from November 2021 to August 2024.After 23 cases were excluded because of complication of prostate cancer,finally 723 patients were included.General clinical data such as age,height,weight,history of smoking and drinking,perioperative parameters,and follow-up data at 1,3 and 6 months after operation were collected.Univariate and multivariate logistic regression analyses were used to identify the clinical risk factors for new-onset urethral stricture after HoLEP.Results The subjected patients had a median age of 66.5(64.0,75.0)years,and a preoperative median prostate volume of 66(45,92)mL,and a median indwelling catheter time of 4(4,5)d.The incidence of new urethral stricture after operation was 5.8%(42/723),with membranous part of the urethra(61.9%)the most common site,followed by the external urethral orifice(21.4%)and the bladder neck(7.1%).Risk factor analysis indicated that low BMI(<18.5 kg/m2)(OR=4.682,P=0.037),young age(OR=0.946,P=0.005),and postoperative urinary tract infection(OR=4.513,P=0.001)were independent risk factors for new-onset urethral stricture after surgery.Prostate volume and indwelling time of urinary catheter had no significant association with the occurrence of new urethral stricture after surgery.Conclusion The occurrence of new-onset urethral stricture after HoLEP is significantly correlated with BMI,age and urinary tract infection.The above 3 factors can be used as better predictors of new-onset urethral stricture after HoLEP.

Neurofibromatosis type 1 (NF1) presents with a diverse range of symptoms that can affect the skin, bones, eyes, central nervous system, and other organs. This article reports the diagnosis and treatment process of a patient with NF1 complicated by bilateral severe-to-profound sensorineural hearing loss. Genetic testing revealed a heterozygous variant of NF1 NM_ 000267.3: c.4054_ 4058del(p.Ser1352LeufsTer20, supporting the diagnosis of NF1. After thorough evaluation, a right cochlear implantation was performed, yielding satisfactory postoperative results. This case suggests that NF1 patients may exhibit phenotypic heterogeneity and atypicality, providing a reference for clinicians in the diagnosis and treatment of such patients.

This study investigated the prevalence and potential mechanisms of gentamicin heterore-sistance in Streptococcus isolates from dairy cows.In this study,A total of 39 Streptococcus isola-ted from raw milk were collected,and the minimum inhibitory concentration(MIC)of gentamicin and other drugs on the isolates was determined by micro broth dilution method,and the K-B paper diffusion method,colony analysis profile(PAP),and resistance stability test were used to investigate the heteroresistance characteristics of Streptococcus,and the mechanism of heteroresis-tance was analyzed based on whole genome sequencing and resequencing.Seven suspected heterore-sistance strains were identified by K-B paper diffusion method,accounting for 17.95％(7/39)of the total number of suspected strains.PAP confirmed that the MIC to MNIC ratio of L147,L108 and L174 was greater than 8,and the frequency of resistant subgroups ranged from 1.38×10-5 to 8.18 × 10-5,which was greater than 1 × 10-7,confirming that they were heteroresistance strains.Resistance stability tests revealed that the resistant subpopulations of all three strains were not stably inherited.Whole-genome sequencing revealed mutations in the ribosomal target genes of aminoglycoside antibiotics,rsmA,rsmB and rsmE,compared with the reference genome,which may lead to heteroresistance to gentamicin in Streptococcus.The occurrence of heteroresistance of Streptococcus to gentamicin is high in dairy sources,so more attention should be paid to the occur-rence of heteroresistance when using gentamicin for clinical treatment.

Objective:To investigate the current status of occupational stress among electronic manufacturing workers in Qingdao and analyze its effect on depressive symptoms and anxiety symptoms.Methods:From July to September 2022, a cluster random sampling method was employed to select frontline workers from 14 electronic manufacturing enterprises in Qingdao as the study subjects. A total of 1134 questionnaires were distributed, with 1000 valid questionnaires collected, yielding an effective response rate of 88.18%. The Core Occupational Stress Scale (COSS), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7) were adopted to assess occupational stress, depressive symptoms, and anxiety symptoms, respectively. Binary logistic regression was employed to analyze influencing factors of occupational stress and its effects on depressive and anxiety symptoms.Results:The detection rates of occupational stress, depressive symptoms, and anxiety symptoms were 15.1% (15/1000), 7.9% (79/1000), and 13.8% (138/1000), respectively. The influencing factor analysis of occupational stress revealed that female gender ( OR=0.621, 95% CI: 0.434-0.890) and weekly working hours of 45-48 hours ( OR=0.537, 95% CI: 0.309-0.935) were protective factors ( P<0.05), while weekly working hours ≥55 hours ( OR=2.176, 95% CI: 1.290-3.670) and shift work ( OR=2.038, 95% CI: 1.412-2.940) were risk factors ( P<0.05). Spearman correlation analysis showed that the COSS score was positively related with the PHQ-9 score and the GAD-7 score ( rs=0.438, 0.289, P<0.01). Workers judged with occupational stress had 3.596 times (95% CI: 2.181-5.931, P<0.001) and 3.121 times (95% CI: 2.046-4.761, P<0.001) higher risks of detecting depressive and anxiety symptoms compared to those without occupational stress. Conclusion:Electronic manufacturing workers in Qingdao experience a certain level of occupational stress, which may increase the risk of developing depressive and anxiety symptoms. Enterprises should implement appropriate interventions to promote workers' mental health.

Objective To evaluate the modeling characteristics and predictive performance of models for predicting post-stroke neurological deterioration(ND)published in existing literatures.Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidance for scoping reviews,a comprehensive search was conducted in PubMed,CINAHL,Cochrane Library,Embase,Web of Science,Scopus,CNKI,Wanfang Data,and VIP databases from inception to December 15,2024.The search strategy combined Medical Subject Headings(MeSH)and free-text terms,with key words including"Stroke""Ischemic Stroke""Neurological Deterioration""Nomograms""Risk Prediction""Predictive Models""卒中""脑梗死""脑出血""神经功能恶化"and"预测模型".Base on the data extraction checklist and critical appraisal,data extraction covered three domains:(1)basic characteristics,including author,publication year,country,study design(retrospective,prospective,registry-based),sample source(single-center,multicenter),stroke subtypes(acute ischemic stroke[AIS]-conservative therapy,AIS-intravenous thrombolysis[IVT],AIS-endovascular therapy[EVT],intracerebral hemorrhage[ICH]),ND time windows(acute[≤72 h],subacute[≤ 7 d],long-term[≤90 d]),and outcome types(single/composite endpoints);(2)model evaluation metrics,including missing data handling(complete-case analysis,multiple imputation),model development methodologies(multivariate Logistic regression,least absolute shrinkage and selection operator regression,machine learning),presentation formats(nomograms,web calculators,risk prediction tool),discrimination(area under the curve,C-index),calibration(Hosmer-Lemeshow test,calibration curve and slope),clinical utility(decision curve analysis[DCA],global metrics Brier score,R2,AIC),sample size(training set,internal validation set,external validation set),sample size requirements(events per variable[EPV]≥10 to mitigate overfitting),and validation(internal/external);(3)predictor features,including selection strategies(prior knowledge-driven,univariate analysis),quantity,and attributes(demographics,medical history,physical examination,treatment intervention information,imaging/laboratory indicators).Predictive models that meet exclusion criteria from prior literature were analyzed by their discrimination,calibration,clinical utility and global metrics.Forest plots were utilized to visualize discrimination(evaluated via difference in area under the curve)of the extracted models.The prediction model risk of bias assessment tool(PROBAST)was applied to assess bias risk and clinical applicability.Occurrence frequencies of the post-stroke neurological deterioration predictors were ranked and the top 6 high-frequency predictors were extracted.Results(1)Among 3 728 screened studies,25 were included based on the inclusion and exclusion criteria.(2)Basic characteristics:retrospective(72％[18/25])and single-center(64％[16/25])designs dominated.With most models targeted on AIS(92％[23/25]),and the rest(8％[2/25])on ICH.ND was primarily defined by neurological scale changes(60％[15/25];e.g.,National Institutes of Health stroke scale[NIHSS]score increase or Glasgow coma scale[GCS]score decrease),with time windows categorized as acute(36％[9/25]),subacute(48％[12/25]),or long-term(16％[4/25]).(3)Model evaluation:multivariate Logistic regression(96％[24/25])and nomograms(88％[22/25])were predominant.Only 24％(6/25)explicitly addressed missing data handling methods,and 52％(13/25)with EPV≥10.The median area under the curve was 0.865(range:0.650-0.981).44％(11/25)of the studies reported calibration curves,and 4％(1/25)reported calibration slopes.All studies utilized DCA to validate their clinical applicability,84％(21/25)of the studies conducted internal validation,while only 32％(8/25)conducted external validation.PROBAST evaluation revealed low overall bias risk in 8％(2/25;no error across participant,predictor,outcome,or analysis domains)and low clinical applicability risk in 44％(11/25;alignment with target populations,accessible predictors,and clinically relevant outcomes)of the studies.(4)Predictors:64％(16/25)of the predictor were screened predominantly through the prior knowledge-driven based strategy.The top 6 high-frequency predictors are NIHSS score(64％[16/25]),age(36％[9/25]),blood glucose/diabetes(36％[9/25]),blood pressure/hypertension(32％[8/25]),the Alberta stroke program early CT score(20％[5/25]),and neutrophil-to-lymphocyte ratio(20％[5/25]).AIS-ND predictors emphasized readily available metrics,such as NIHSS(65％[15/23]),age(35％[8/23]),while ICH-ND primarily relied on imaging markers(e.g.,baseline hematoma volume[2/2],location[1/2]).Conclusion Current post-stroke ND predictive models demonstrate satisfactory performance on discrimination and multimodal integration,but their practical application are hindered by insufficient calibration quantification,high bias risk,and limited clinical translatability.

As one of the core theories of spleen governing transportation and transformation in the traditional Chinese medicine visceral manifestation theory,the modern biological basis of"spleen qi disperses essence"has not been fully elucidated.Lipids are one of the three major nutrients in the body,which are derived from exogenous absorption or endogenous transformation,and belong to the category of"grease"and"essence"substances in traditional Chinese medicine.Because of their hydrophobic nature,lipids require apolipoproteins to be transported in the bloodstream and used by the body;similarly,essence also needs spleen qi transformation to be distributed throughout the body and exert their nourishing effects,revealing a certain degree of inherent unity between the two.When the spleen qi functions properly,essence dispersal is orderly and lipid metabolism remains in homeostatic balance;if spleen deficient leads to impaired transportation,the essence will not be distributed,and the lipid turbidity will accumulate,causing disease.Classic strengthening spleen prescriptions such as Zexie Decoction,can reshape lipid homeostasis by regulating apolipoproteins.Based on apolipoprotein-mediated lipid metabolism,this paper explores the modern molecular biology basis of the theory of"spleen qi disperses essence,"which provides novel insights for enriching the modern research of traditional Chinese medicine visceral manifestation theory,and lays the foundation for clinical practice and theoretical innovation in the treatment of metabolic diseases from the spleen.

Thyroid-associated ophthalmopathy(TAO) is an organ-specific autoimmune disease closely related to hy-perthyroidism,but it may also be detected in chronic autoimmune thyroiditis patients with normal thyroid functions or hy-pothyroidism.The clinical manifestations of TAO are diverse,and the progression of the disease varies.Therefore,accu-rately assessing its activity and the extent of lesions is crucial for guiding clinical treatment.Imaging examinations play an important role in the clinical diagnosis and evaluation of TAO.Commonly used methods include computed tomography(CT)and magnetic resonance imaging(MRI).In this article,the current applications of CT and MRI to the evaluation of TAO were reviewed,aiming to assist clinicians in selecting appropriate imaging modalities for accurate disease staging and formulating more rational treatment strategies.

In July 2024,the Diagnosis Related Groups(DRG)2.0 is released based on the Notice from the National Healthcare Security Administration on Issuing the DRG 2.0 and Deepening the Relevant Work.Compared with DRG 1.1,version 2.0 was established based on a wider range of suggestions regarding the Adjacent Diagnosis Related Groups(ADRG),Major Comorbidity or Complication(MCC),and Comorbidity or Complication(CC)from various institutions.A list of disease diagnoses and surgical operations that are not used as grouping rules was compiled,and grouping efficacy was further improved by upgrading the algorithms for MCC and CC with the help of AI.Meanwhile,it is necessary to pay more attention to the number of cases of ADRG,the better methods to list the MCC/CC,the suggestions of various doctors and continuously standardize the data and update the grouping scheme of DRG.

Objective:To investigate the effects of remote ischemic preconditioning (RIPC) on myocardial injury after non-cardiac surgery (MINS) in elderly patients with hip fracture.Methods:A prospective randomized controlled trial was conducted on 78 elderly patients with hip fracture admitted to the Seventh Medical Center of the PLA General Hospital between October 2023 and September 2024. The patients were divided into RIPC group and non-RIPC group using a random number table. They were treated with closed reduction internal fixation, open reduction internal fixation, or hip arthroplasty for hip fracture under regional anesthesia. The RIPC group received RIPC intervention on the day before surgery and after entering the operating room on the day of surgery (3 cycles of 5-minute upper limb exsanguination followed by 5-minute reperfusion using an inflatable tourniquet cuff). The non-RIPC group received the same perioperative management as the RIPC group except RIPC. Plasma high-sensitivity cardiac troponin I (hs-cTnI) concentrations were measured at admission, immediately after surgery, on the morning of the first postoperative day, and on the morning of the third postoperative day and MINS incidence was calculated based on the hs-cTnI concentrations. The incidence of MINS within 3 days postoperatively and the intraoperative complications were compared in the overall cohort and in age-stratified groups (<80 years, ≥80 years). The local adverse reactions at the RIPC application sites were observed within 3 days after surgery.Results:Among the 78 elderly patients with hip fracture, including 21 males and 57 females, aged 60-99 years [79.5(70.0, 87.0)years], 40 were assigned to the RIPC group and 38 to the non-RIPC group. No significant difference was found in the general data of the two groups. There was no significant difference in the overall MINS incidence between the two groups ( P>0.05). In the patients aged <80 years, no MINS incidence was found (0/21) in the RIPC group, compared with 22% (4/18) in the non-RIPC group ( P<0.05), while in the patients aged ≥80 years, no significant difference in MINS incidence was observed between the two groups ( P>0.05). There were no significant differences in intraoperative complication rates in the overall cohort, patients aged <80 years, or patients aged ≥80 years ( P>0.05). None of the patients had local adverse reactions at the RIPC application sites. Conclusion:For elderly patients with hip fracture who received regional anesthesia, RIPC can significantly reduce the incidence of MINS in patients aged <80 years, but exerts no significant effect on MINS incidence in the overall cohort or in patients aged ≥80 years.