Abstract In April 2021, type Ⅰ vaccine-derived poliovirus (VDPV) was detected from two fecal samples of a male infant with acute flaccid paralysis (AFP) in Zhejiang Province when he was admitted to the Children's Hospital Affiliated to Fudan University in Shanghai, with 12 and 14 nucleotide mutations in the VP1 region, respectively. The case had a history of immunization with three doses of poliovirus vaccines, and grade Ⅲ proximal muscle strength and grade Ⅱ distal muscle strength of the right lower limb. After symptomatic treatment, the activity of the right lower limb and the muscle strength was significantly restored, thus he was discharged. VDPV was not detected from subsequent (the 8th to 12th) fecal samples of the case and fecal samples of close contacts. No similar cases were found in medical institutions in the county, surrounding areas, neighboring villages or towns. Since the case did not exhibit clinical symptoms of poliomyelitis caused by VDPV, poliomyelitis was excluded, and the case was diagnosed with hemophilia type A based on the epidemiological investigation, laboratory tests, and the history of poliomyelitis vaccination. This event involved cross-provincial (municipal) cooperation and was responsed promptly, preventing further spread of the virus. It suggested that the sensitivity of the AFP case surveillance system should be maintained, environmental monitoring methods should be increased, and the poliomyelitis vaccination should be promoted to prevent the spread of the virus.

Objective To explore the effects of bronchoalveolar lavage combined with microbiological rapid on-site evaluation in potential donor lung maintenance.Methods Brain death patients who met the inclusion criteria and were admitted to the Intensive Care Unit(ICU)of Calmette Hospital Affiliated to Kunming Medical University from September 2020 to December 2022 were selected for bronchoalveolar lavage(BAL)and(BAL)and the lavage fluid were collected for M-ROSE to compare the pathogen detection rate and initial diagnosis time.According to the positive results of the microbiological rapid on-site evaluation,patients with the brain death were treated with empirical anti-infective therapy,and the oxygenation index,chest X-ray score,and the infection index(WBC,CRP,PCT)of anti-infective treatment 48 hours were evaluated.Results 1.Comparison of the detection rate of pathogenic microorganisms:The results of M-ROSE were highly consistent with a routine microbiological smear(Kappa = 0.921,P<0.001).2.Comparison of diagnostic time:The initial diagnosis time of M-ROSE was significantly lower than routine microbiological smear time and microbial culture time(P<0.001).3.Comparison of therapeutic effects of anti-infective therapy for 48 hours:There was no significant difference in oxygenation index,white blood cells and hypersensitive C-reactive protein before and after the anti-infective treatment(P>0.05).There were significant differences in procalcitonin and chest X-ray before and after the anti-infective treatment(P<0.05).Conclusion Bronchoalveolar lavage combined with microbiological rapid on-site evaluation has the high timeliness in the diagnosis of potential donor pulmonary infection,which can provide a preliminary basis for the early anti-infective therapy of donor lung maintenance.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To systematically review the value of rapid on-site evaluation (ROSE) for diagnosing pulmonary and mediastinal lesions with endobronchial ultrasound (EBUS). Methods PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases were searched by computer to collect the studies of ROSE and EBUS in the diagnosis of pulmonary and mediastinal lesions from inception to August 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was implemented by RevMan 5.4 and Stata 12.0 software. Results A total of 15 studies (9 retrospective studies and 6 prospective studies) with 3 577 patients were included. The meta-analysis results of main outcomes showed that the adequacy of the sample (RD=0.10, 95%CI 0.05 to 0.15, P<0.000 1), overall diagnosis rate (RD=0.07, 95%CI 0.04 to 0.10, P<0.000 1) and the diagnosis rate of the malignant lesion (RD=0.06, 95%CI 0.02 to 0.09, P=0.004) of the ROSE combined with EBUS group were significantly higher than those of the EBUS group. Subgroup analysis showed that the diagnosis rates of pulmonary lesions (RD=0.12, 95%CI 0.08 to 0.17, P<0.000 01) and mediastinal lesions (RD=0.06, 95%CI 0.01 to 0.12, P=0.02) in the ROSE group was significantly higher than those in the EBUS group. The overall diagnosis rate and malignant diagnosis rate of ROSE combined with EBUS were 90% and 92%. The meta-analysis results of secondary outcomes showed that the number of lesions punctures (MD=–1.16, 95%CI –1.89 to –0.43, P=0.002) in the ROSE combined with EBUS group were significantly less than that in the EBUS group; there was no statistical difference in operation time (MD=0.09, 95%CI –5.22 to 5.39, P=0.97) or incidence of complications (RD=–0.06, 95%CI –0.13 to 0.01, P=0.1) between the two groups. Conclusion ROSE can improve the diagnostic efficiency of EBUS in pulmonary and mediastinal lesions, and has the value of the clinical application.

Objective To screen key genes for ferroptosis in atherosclerosis(AS)using bioinformatics methods and analyze the biological functions of key genes to gain an in-depth understanding of the pathogenesis of AS.Methods AS gene expression profile chip dataset GSE100927 was downloaded from the Gene Expression Omnibus(GEO)database.P＜0.05 and|logFC＞1|were used as the conditions to screen the differential genes of AS.These genes were intersected with ferroptosis gene dataset to screen out the genes related to AS ferroptosis.Gene ontology(GO)functional annotation and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were carried out.The STRING online analysis tool combined with Cytoscape visualization software was subsequently used to mine genes that play a key role in the biological process of AS,and the AS dataset GSE9874 was used as the verification set to verify the expression of key genes.Blood samples from 30 confirmed AS patients in the cardiovascular department of our hospital from January to March 2023 were collected as the experimental group,while blood samples from 20 healthy volunteers were collected as the control group.Sample RNA was extracted,and quantitative real time polymerase chain reaction(qRT-PCR)was used to verify the selected genes.Results A total of 10 differential genes related to ferroptosis were screened by bioinformatics method.GO functional enrichment analysis showed that differential genes were mainly involved in inflammation,apoptosis,oxidative stress and other biological processes,while KEGG pathway enrichment analysis showed that differential genes were mainly involved in ferroptosis,HIF-1 signaling pathway,and leukocyte migration pathway through endothelial cells.Seven key modules of gene construction were screened out through the protein interaction network,which were FTL,SLC40A1,CYBB,NCF2,HMOX1,DPP4 and ALOX5.GSE9874 was used for verification,and 5 key genes including ALOX5,DPP4,FTL,SLC40A1 and NCF2 were finally screened out.The expression detection of key genes in clinical samples by qRT-PCR showed that compared with the control group,the up-regulated genes in blood of AS group were DPP4(t=1.795,P=0.046),FTL(t=2.218,P=0.029)and SLC40A1(t=2.859,P=0.009),and the down-regulated genes were ALOX5(t=8.039,P＜0.001)and NCF2(t=11.867,P＜0.001),and the differences were significant.The experimental results were consistent with the results of bioinformatics analysis.Subgroup analysis showed that DPP4 expression in plaque group was higher than that in intima thickening group,and the difference was significant(t=2.843,P=0.036).Conclusion The key genes of ferroptosis screened by bioinformatics are AS,ALOX5,DPP4,FTL,SLC40A1 and NCF2,which may be potential targets for the diagnosis and treatment of AS,providing new ideas for the clinical diagnosis and treatment of AS.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.

Abstract Vaccine-hypervariable poliovirus type Ⅲ was detected in an acute flaccid paralysis infant at age of 6 months in Zhejiang Province in June, 2021, and the isolated and incubated virus had six nucleotide variations in the VP1 region as compared to the poliovirus Sabin vaccine strain. The infant had a history of three-dose poliovirus vaccination, and grade 2 muscle strength of the left upper limb upon onset. He was clinically diagnosed with cellulitis of the left shoulder, and recovered to normal following treatment. No abnormality was detected in the nervous system, and the infant was cured and discharged from hospital. No vaccine-hypervariable poliovirus was detected in subsequent infant' clinical samples or in close contacts, and no similar cases were identified during the active case detection by county/district medical institutions and among community populations. Since the infant did not present poliomyelitis-related clinical symptoms caused by vaccine-hypervariable poliovirus, poliomyelitis was excluded. The vaccine-hypervariable poliovirus was not spread because of timely identification and effective responses, suggesting the urgent need to maintain the sensitivity of the acute flaccid paralysis surveillance system and improve the coverage of poliovirus vaccination, so as to inhibit the transmission of poliovirus.

Objective:Summarizing the clinical characteristics of extraneural metastasis in childhood medulloblastoma.Methods:A total of 616 cases with medulloblastoma treated in Beijing Shijitan Hospital from April 2010 to April 2019 were analyzed retrospectively, among which 11 cases developed extraneural metastasis.The age of onset, location and time of extraneural metastasis, pathological and molecular typing, treatment and prognosis were descriptively analyzed.The differences of blood biochemical indexes between medulloblastoma cases with and without extraneural metastasis were statistically analyzed by t test. Results:As of February 2020, the median follow-up period was 16 months (ranging from 3 to 69 months). Eleven cases, including 8 males and 3 females, were diagnosed with extraneural metastasis, with the incidence being about 1.8%.The median age of medulloblastoma was 6 years (2-10 years), and the median age at presentation of extraneural metastasis was 7 years (2-12 years). Extraneural metastasis occurred from 0.5 months to 38.0 months after the operation, and the affected location includes bone (6 cases), bone marrow (3 cases), lung (3 cases), pelvis (2 cases) and abdominal cavity (1 case). In these patients, the range of lactic dehydrogenase (LDH) was (2 298.00±1 570.70) U/L and neuron-specific enolase (NSE) was (201.00±68.34) μg/L, which were significantly higher than those in patients without extraneural metastasis [(249.50±46.28) U/L and (22.80±7.12) μg/L, all P<0.05]. Partial patients were treated with chemotherapy, while the majority of them were treated with palliative treatment in the terminal stage, with the survival period mostly less than 10 months. Conclusions:Although there is a low incidence of extraneural metastasis in medulloblastoma pediatric patients, the prognosis of these patients with extraneural metastasis is poor and most of them would die within one year.The most common sites include bone, followed by bone marrow and lungs, which may be related to the spread of cerebrospinal fluid and the increased levels of LDH and NSE.

Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.