Objective To explore predictive factors of severe community-acquired pneumonia (CAP) complicated with respiratory failure (RF) and to develop and internally validate a clinical prediction model. Methods A retrospective study was conducted on 350 patients with severe CAP admitted to Tianyou Hospital Affiliated to Wuhan University of Science and Technology from September 2022 to December 2024. Patients were randomly divided into a training set (n＝245) and a validation set (n＝105) in a 7∶3 ratio, and further categorized into RF and non-RF groups. LASSO regression was applied to optimize variable selection. Multivariate logistic analysis was used to construct the prediction model, followed by internal validation. Results Univariate regression analysis identified male, hypertension, diabetes, coronary heart disease, age, CURB-65 score, white blood cell count, neutrophil count, C-reactive protein (CRP), serum amyloid A, procalcitonin, and hospital stay as risk factors for RF in severe CAP, while albumin level was a protective factor. LASSO regression selected CURB-65 score, albumin level, and CRP for inclusion in the final model. The area under the receiver operating characteristic curve was 0.903 in the training set and 0.919 in the validation set. Calibration curve analysis demonstrated excellent agreement between predicted and observed probabilities in both sets, and Hosmer-Lemeshow goodness-of-fit tests indicated no significant deviations. Threshold probabilities ranged from 0.01 to 0.99 in both training and validation sets. Conclusions CURB-65 score, albumin level, and CRP are independent predictors of RF in severe CAP. The clinical prediction model based on these factors exhibits strong discrimination, calibration, goodness-of-fit, and clinical utility.

AIM To study the chemical constituents from Ganoderma angustisporum J.H.Xing,B.K.Cui&Y.C.Dai and their α-glucosidase inhibitory activities.METHODS The ethyl acetate extract from G.angustisporum was isolated and purified by silica gel,ODS,TLC and HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.pNPG method was used to evaluate their α-glucosidase inhibitory activities.RESULTS Seven compounds were isolated and identified as N-acetyl-L-phenylalanine ethyl ester(1),N-acetyl-L-phenylalanine methyl ester(2),4-hydroxy-17R-methylincisterol(3),6,8-di-O-methylaverufin(4),aversin(5),methyl 2-(4-hydroxyphenyl)aceate(6),5-toluene-1,3-diol(7).Compounds 1-2,4-7 showed inhibitory activities of α-glucosidase with IC50 values being(33.80±0.47),(45.45±7.95),(48.80±5.86),(39.48±2.82),(41.47±6.68),(55.38±10.12)μmol/L,and compound 1 showed good inhibitory activity.CONCLUSION Compound 1 is a new natural product.Compounds 2-7 are isolated from genus Ganoderma for the first time.Compounds 1-2,4-7 have α-glucosidase inhibitory activities.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective To investigate the effect of Ophiopogonin D on lipopolysaccharide(LPS)-induced apoptosis of alveolar epithelial cells by regulating the interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A549 AT Ⅱ cells cultured in vitro were randomly divided into four groups:control group,LPS group,LPS+Ophiopogonin D group,LPS+Ophiopogonin D+colivelin(JAK2/STAT3 signal activator)group,except for the control group,and cells in all other groups were established injury models while being grouped with Ophiopogonin D and colivelin for treatment.Cell counting kit-8(CCK-8)experiment and flow cytometry were applied to detect cell proliferation and apoptosis in each group;Western blotting was applied to detect the expression of IL-6/JAK2/STAT3 signaling pathway proteins of cells in each group.Results The apoptosis rates of A549 cells in control group,LPS group,LPS+Ophiopogonin D group and LPS+Ophiopogonin D+colivelin group were(2.52±0.73)％,(52.43±4.14)％,(1.67±0.52)％and(47.94±3.43)％;IL-6 protein levels were 0.14±0.03,0.49±0.05,0.17±0.04 and 0.45±0.06,and p-JAK2/JAK2 protein levels were 0.17±0.04,0.64±0.08,0.19±0.06 and 0.61±0.07;p-STAT3/STAT3 protein levels were 0.20±0.06,0.69±0.10,0.22±0.07 and 0.65±0.09;the apoptosis rates of AT Ⅱ cells were(3.01±0.69)％,(55.16±3.94)％,(2.35±0.71)％and(50.28±3.78)％;the levels of IL-6 protein were 0.11±0.03,0.87±0.13,0.19±0.04 and 0.84±0.12;the p-JAK2/JAK2 protein levels were 0.13±0.04,0.56±0.08,0.15±0.03 and 0.53±0.07;p-STAT3/STAT3 protein levels were 0.30±0.08,0.79±0.14,0.33±0.09 and 0.75±0.13.The above indexes:control group,LPS+Ophiopogonin D group compared with LPS group,LPS+Ophiopogonin D+colivelin group compared with LPS+Ophiopogonin D group,the differences were statistically significant(all P＜0.05).Conclusion Ophiopogonin D can reduce LPS induced inflammation and oxidative stress levels by inhibiting the activation of IL-6/JAK2/STAT3 signaling pathway,ultimately reducing LPS-induced apoptosis of alveolar epithelial cells.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Ceria nanoparticles(CeO2 NPs)have become popular materials in biomedical and industrial fields due to theirpotential applications in anti-oxidation,cancer therapy,photocatalytic degradation of pollutants,sensors,etc.Many methods,including gas phase,solid phase,liquid phase,and the newly proposed green synthesis method,have been reported for the synthesis of CeO2 NPs.Due to the wide application of CeO2 NPs,concerns about their adverse impacts on human health have been raised.This review covers recent studies on the biomedical applications of CeO2 NPs,including their use in the treatment of various diseases(e.g.,Alzheimer's disease,ischemic stroke,retinal damage,chronic inflammation,and cancer).CeO2 NP toxicity is discussed in terms of the different systems of the human body(e.g.,cytotoxicity,genotoxicity,respiratory toxicity,neurotoxicity,and hepatotoxicity).This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the application effect of grid-like locator in percutaneous transforaminal endoscopic discectomy(TESSYS)technology for lumbar disc herniation(LDH)in young adults.Methods Using a randomized controlled study method,102 young adults with LDH were included and divided into the control group and the observation group,with 51 cases in each group.Patients in the control group underwent TESSYS technology,while patients in the observation group underwent TESSYS technology with a grid-like locator.The perioperative indicators,complications,good to excellent surgical rate,the pre-and post-operative pain mediators[5-hydroxy-tryptamine(5-HT),substance P(SP)],Oswestry disability index(ODI),visual analogue scale(VAS),Cobb angle,and lumbar curvature index were compared between the two groups.Results The operation time of patients in the observation group was shorter than that of the control group,and the intraoperative blood loss and the number of intraoperative fluoroscopy were less than those of the control group(P＜0.05).The levels of serum 5-HT and SP,and VAS score 3 days after surgery in the observation group were lower than those in the control group(P＜0.05).There was no significant difference in the serum pain mediators,VAS scores,ODI scores,Cobb angles,or lumbar curvature indexes 3 months,6 months,and 12 months after surgery between the two groups(P＞0.05).There was no significant difference between the observation group and the control group in the incidence of complications(4.16％vs.10.64％),good to excellent surgical rate(89.58％vs.85.11％)12 months after surgery(P＞0.05).Conclusion The application of a grid-like locator in TESSYS technology for young adults with LDH can help to reduce the intraoperative fluoroscopy,alleviate pain symptoms,and shorten the operation time.

Objective To construct a non-drug intervention program for acute chemotherapy-related nausea and vomiting in children with cancer and to evaluate its efficacy.Methods Through literature review and Delphi expert correspondence,a non-drug intervention program for acute chemotherapy-related nausea and vomiting in children with cancer was constructed.By the convenience sampling method,200 consecutive children who received chemotherapy in the neurosurgery department of a tertiary children's hospital in Zhejiang province from February 1 to October 31,2023 were included as the application subjects,with 100 cases in an experimental group and 100 cases in a control group.The experimental group applied the non-drug intervention program of acute chemotherapy-related nausea and vomiting in children with cancer,and the routine measures were applied in the control group.The incidence of nausea and vomiting,severity of vomiting,compliance rate of normal sleep duration and incidence of negative emotions were compared between the 2 groups.Results The recovery rate of the valid questionnaire in 2 rounds of expert letter inquiry was 100％,and the expert authority coefficient was 0.836.The Kendall harmony coefficients were 0.471 and 0.820(P＜0.001),and the final non-drug intervention program for pediatric acute chemotherapy-related nausea and vomiting included 5 primary,14 secondary and 18 tertiary items.The results showed that the incidence of nausea,vomiting and negative emotions in the experimental group were lower than that in the control group,with statistically significant differences(P＜0.05).The severity of vomiting was less than it in the control group,with statistically significant difference(P＜0.05).The standard rate of normal sleep time was higher than that of the control group,and the difference was statistically significant(all P＜0.05).Conclusion The non-drug intervention program of chemotherapy-related nausea and vomiting in children is scientific and feasible,and the implementation of the program can reduce the incidence of nausea,vomiting and negative emotions,reduce the severity of vomiting,and improve the standard rate of normal bedtime in children.