ObjectiveTo analyze the risk factors for long-term cardiovascular events in patients undergoing long-term peritoneal dialysis （PD）， and to construct and validate a visual nomogram prediction model based on multiple parameters. MethodsA prospective cohort study was conducted， consecutively enrolling 248 maintenance PD patients （dialysis duration ≥ 3 months）. Demographic characteristics， clinical indicators， laboratory parameters， and echocardiographic indices （including left ventricular ejection fraction ［LVEF］， ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity （E/e’）， etc.） were collected. The composite endpoint was defined as the occurrence of cardiovascular events or cardiovascular death， with non-cardiovascular death as the competing risk and loss to follow-up or the end of follow-up as censoring events. Fine-Gray competing risks model was used to screen independent predictors， based on which a nomogram model was constructed. Internal validation was performed using the Bootstrap method （1 000 resamplings）， and the concordance index （C-index） and time-dependent receiver operating characteristic （time-dependent ROC） curve were calculated to evaluate the model performance. ResultsWith a median follow-up of 29 months （interquartile range： 24–35 months）， 88 patients （35.48%） reached the composite endpoint， including 80 cases of cardiovascular events and 8 cases of cardiovascular death， and 4 patients died of non-cardiovascular causes. Multivariate Fine-Gray analysis revealed that age， diabetes mellitus， hemoglobin （HGB） level and E/e' ratio were independent influencing factors of the composite endpoint. Specifically， each 1-year increase in age was associated with a 3.0% increase in the risk of the composite endpoint （HR=1.030， P=0.006）； patients with diabetes mellitus had a 167.9% higher risk compared with non-diabetic patients （HR=2.679， P=0.007）； each 1g/L increase in HGB level contributed to a 1.5% reduction in the risk （HR=0.985， P=0.003）； and each 0.1 increase in E/e' ratio led to a 7.2% increase in the risk （HR=1.072， P=0.045）. The nomogram model had a C-index of 0.76 （95% CI： 0.698–0.820）， and the AUC of the time-dependent ROC curve reached 0.849 at 23 months of follow-up. ConclusionIncreased age， complicated with diabetes mellitus， decreased HGB， and elevated E/e' ratio are independent risk factors of long-term occurrence of cardiovascular events and cardiovascular death in patients undergoing long-term PD. The nomogram model constructed based on the above variables has good predictive value and clinical applicability， which can provide a reference for cardiovascular risk stratification and individualized intervention in long-term PD patients.

ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents， providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem， ChemicalBook， and ChemSpider， combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography （HPLC）. ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents， including 69 flavonoids， 36 terpenoids， 23 phenylpropanoids， 8 phenylethanoid glycosides， and 19 other types of constituents. In the established quantitative analysis method， the seven main constituents showed good linearity within their respective linear ranges. The precision， repeatability， stability， and spike recovery all met the required standards. The results showed that the content ranges of geniposide， liquiritin， hesperidin， arctiin， baicalin， oroxylin A-7-O-β-D-glucuronide， and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25， 1.20-7.64， 5.45-7.45， 22.97-33.51， 29.95-39.07， 2.58-4.80， and 6.56-9.31 mg·g^-1， respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang， clarifying that its material basis is primarily composed of flavonoids， terpenoids， phenylethanoid glycosides， and phenylpropanoids. Furthermore， it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control， action mechanism， and clinical application of this formula.

Objective:To investigate the immunological mechanism by which grifola frondosa extract improves colonic tissue inflammation in rats with ulcerative colitis(UC)through the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)signaling pathway.Methods:Forty male SD rats were randomly divided into five groups:blank group,model group,sulfasalazine treatment group(SASP group),grifola frondosa extract treatment group(GF group),and sulfasalazine combined with grifola frondosa extract treatment group(SASP+GF group).UC model was established using a 3%dextran sulfate sodium(DSS)free drinking method.After one week,each treatment group received sulfasalazine 0.3 g/(kg·d),grifola frondosa extract 10 mg/(kg·d),and combination of both drugs by gavage.During the experiment,the general condition of the rats was observed,the disease activity index(DAI)score was re-corded and the protein content and positive expression levels of SPHK1,S1P,tumor necrosis factor receptor-associated factor 2(TRAF2)and TNF-α in rat colon tissue were detected by immunohistochemistry.mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in rat colon tissue were measured by RT-qPCR and Western blot.Results:Compared with the blank group,the general condition of the model group rats were poor,the DAI score was significantly increased,and the protein positive expres-sion,mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in colon tissue were significantly increased(P<0.01).Compared with the model group,the general condition of the rats in each treatment group improved significantly,the DAI score was decreased(P<0.01),and the positive expression of each target protein was significantly reduced(P<0.01),especially in the GF group and SASP+GF group;the mRNA and protein expression levels of SPHK1 and TRAF2 were reduced to varying degrees(P<0.01 or P<0.05),while the mRNA and protein expression levels of S1P and TNF-α only decreased significantly in the GF group and SASP+GF group(P<0.01).Compared with the SASP group,the GF group only showed a decrease in SPHK1 protein expression,TNF-α mRNA,and protein expression levels,while the SASP+GF group showed significant reductions in all targets(P<0.01 or P<0.05).Compared with the GF group,the SASP+GF group showed significant reductions in SPHK1 protein positive expression and content,S1P mRNA expression levels,and TNF-α protein content(P<0.05 or P<0.01).Conclusion:Grifola frondosa extract may alleviate co-lonic tissue inflammation in rats with UC by inhibiting the activation of the SPHK1/S1P pathway,restoring intestinal mucosal barrier function,and improving symptoms of UC.

Lung cancer is a serious pulmonary tumor,with exacerbation of chronic lung inflammation being a precursor to the development of lung cancer.Relevant animal models are widely used in experimental research,to gain a deeper understanding of the pathogenesis of lung cancer and to develop preventive treatment strategies.Induced lung cancer animal models are of particular importance for understanding the transition from chronic lung inflammation to lung cancer.Early intervention is crucial for the prevention and treatment of lung cancer.Here we review the recent literature regarding the inducing factors for lung cancer,including carcinogens(e.g.nicotine-derived nitrosamine ketone,benzopyrene,diethylnirtosamine atmospheric fine particulate matter(PM2.5),coal smoke,heavy metal ions,radiation,and biological infections).We also summarize animal models of lung inflammation and cancer transformation induced by these factors,discuss the mechanisms by which relevant carcinogens induce lung cancer,analyze the advantages and limitations of the animal models,and consider future development directions.This review aims is to provide a valuable reference for the future establishment of relevant models.

This study aims to investigate the effects of aflatoxin B1(AFB1)on the infection and replication of porcine delta coronavirus(PDCoV).Porcine small intestinal epithelial cells(IPEC-J2),porcine kidney cells(LLC-PK)and swine testis cells(ST)were used as models,and CCK-8 method was used to detect the safe mass concentration range of AFB1 on the three cell lines.Each cell line was divided into the blank control group,AFB1 treatment group,PDCoV treatment group and AFB1 and the PDCoV co-treatment group.The cells were treated with safe mass concentration of AFB1 for 12 h,and then treated with PDCoV for 20 h.Total RNA and total protein were extrac-ted from the cells.The effects of AFB1 on PDCoV infection and replication were detected by qPCR,Western blot and cell immunofluorescence tests.The results showed that compared with the PDCoV treatment group,the mRNA and N protein of viral S protein in the AFB1 and PDCoV co-treatment group were significantly increased(P＜0.05),and a significantly higher fluorescence of PDCoV N protein is also visibly present in the co-treatment group,and there was a significant difference between the two groups.The results showed that AFB1 could promote the infection and replication of PDCoV.It provides important data that AFB1 can promote the infection replication of PDCoV and provides a new idea for the prevention and treatment of PDCoV.

Objective:To investigate the immunological mechanism by which grifola frondosa extract improves colonic tissue inflammation in rats with ulcerative colitis(UC)through the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)signaling pathway.Methods:Forty male SD rats were randomly divided into five groups:blank group,model group,sulfasalazine treatment group(SASP group),grifola frondosa extract treatment group(GF group),and sulfasalazine combined with grifola frondosa extract treatment group(SASP+GF group).UC model was established using a 3%dextran sulfate sodium(DSS)free drinking method.After one week,each treatment group received sulfasalazine 0.3 g/(kg·d),grifola frondosa extract 10 mg/(kg·d),and combination of both drugs by gavage.During the experiment,the general condition of the rats was observed,the disease activity index(DAI)score was re-corded and the protein content and positive expression levels of SPHK1,S1P,tumor necrosis factor receptor-associated factor 2(TRAF2)and TNF-α in rat colon tissue were detected by immunohistochemistry.mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in rat colon tissue were measured by RT-qPCR and Western blot.Results:Compared with the blank group,the general condition of the model group rats were poor,the DAI score was significantly increased,and the protein positive expres-sion,mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in colon tissue were significantly increased(P<0.01).Compared with the model group,the general condition of the rats in each treatment group improved significantly,the DAI score was decreased(P<0.01),and the positive expression of each target protein was significantly reduced(P<0.01),especially in the GF group and SASP+GF group;the mRNA and protein expression levels of SPHK1 and TRAF2 were reduced to varying degrees(P<0.01 or P<0.05),while the mRNA and protein expression levels of S1P and TNF-α only decreased significantly in the GF group and SASP+GF group(P<0.01).Compared with the SASP group,the GF group only showed a decrease in SPHK1 protein expression,TNF-α mRNA,and protein expression levels,while the SASP+GF group showed significant reductions in all targets(P<0.01 or P<0.05).Compared with the GF group,the SASP+GF group showed significant reductions in SPHK1 protein positive expression and content,S1P mRNA expression levels,and TNF-α protein content(P<0.05 or P<0.01).Conclusion:Grifola frondosa extract may alleviate co-lonic tissue inflammation in rats with UC by inhibiting the activation of the SPHK1/S1P pathway,restoring intestinal mucosal barrier function,and improving symptoms of UC.

Objective:To investigate the magnetic resonance imaging (MRI) features of non-midline atypical medulloblastoma (MB) in children and analyze the causes of misdiagnosis, so as to improve the understanding and diagnosis of MB.Methods:The clinical and imaging data of 12 cases with non-midline atypical MB confirmed by pathology in Hunan Children′s Hospital from September 2018 to August 2023 were retrospectively analyzed. 12 cases underwent MRI plain scan, 11 cases underwent enhanced scan, and 10 cases underwent diffusion weighted imaging (DWI) and magnetic sensitivity weighted imaging (SWI). The location, morphology, peritumoral edema, size, signal characteristics (cystic lesion or hemorrhage), diffusion and enhancement of the tumor were observed, and the causes of misdiagnosis were analyzed.Results:Among the 12 cases, 9 cases were single, 4 cases were located in the cerebellar hemisphere, 2 cases were in the cerebellopontine angle (CPA), 2 cases were in the brain stem and CPA, and 1 case was in the left parietal lobe. There were 3 cases of multiple lesions, 1 case was located in the right pontine arm and cerebellar hemisphere (2 masses), 1 case was multiple lesions in bilateral cerebellar hemisphere, and 1 case was multiple nodular lesions in the cerebellar vermis mass and left cerebellar hemisphere. 6 cases were irregular in shape and 6 cases were quasi-circular. There were 3 cases without cystic change and 9 cases with varying degrees of cystic change (5 with large cystic change and 4 with small cystic change). 3 cases of hemorrhage, no calcification, 10 cases of DWI showed varying degrees of limited diffusion; 11 cases of enhanced scanning showed mild to obvious enhancement; There were 2 cases without peritumoral edema and 10 cases with mild to moderate peritumoral edema. There were 11 cases with supratentorial hydrocephalus and interstitial cerebral edema, and 1 case without hydrocephalus. 5 cases complicated with subtonsillar hernia; 9 cases were misdiagnosed before operation. Among them, 3 cases were misdiagnosed as high-grade glioma, 3 as low-grade glioma (1 of which was diagnosed as hair-cell astrocytoma), 2 as ependymoma, and 1 as atypical teratoma/rhabdomyoma.Conclusions:The MRI manifestations of non-midline atypical MB in children are varied. Combined with the location of the disease, age and focal signal characteristics, non-midline atypical MB can be included in the diagnostic range after the exclusion diagnosis, which can improve the preoperative diagnosis accuracy of this disease.

Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology* ; Autophagy/immunology* ; Humans ; Animals ; Immunity, Innate ; Adaptive Immunity ; Disease Progression ; Immune System/immunology*

The master protocol design encompasses a comprehensive clinical trial protocol containing multiple sub-protocols, which can be used to evaluate the clinical intervention effects of various drugs or vaccines on various diseases. Particularly, this design strategy represents an efficient and innovative approach to trial design in the context of precision medicine. The master protocol design can be used for emerging infectious diseases and urgent vaccine development in complex situations. This review aims to outline the types and concepts of master protocol design, analyze the key points and details, and discuss its application scenarios in vaccine clinical evaluations. Additionally, it will explore potential challenges that may arise during implementation to provide references for optimizing emergency clinical trial designs of infectious disease vaccines in China.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.