The development of multidrug resistance (MDR) to chemotherapy remains a major trouble in the treatment of tumors,and the mechanisms of MDR are complicated.The classic mechanisms involve the overexpression of multidrug resistance-associated protein,inhibition of cell apoptosis,abnormality of enzyme system and gene repair.Studies in recent years have shown that the mechanisms of MDR are also closely related with tumor stem cells,tumor microenvironment and abnormality of signal transduction pathways.

Objective:To raise awareness of acute myeloid leukemia (AML) combined with lymphoblastic lymphoma (LBL) in children.Methods:The clinical characteristics, diagnostic methods, treatment plans and prognosis of a child with AML combined with LBL who was admitted to the First Affiliated Hospital of Zhengzhou University in April 2016 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was an 11-year-old boy with fever, abnormal hemogram and cervical lymph node enlargement as clinical manifestations. A biopsy of the cervical lymph node was performed and the patient was diagnosed as T-lymphoblastic lymphoma (T-LBL). After the bone marrow morphology, immunology, cytogenetics and molecular biology (MICM) classification examination, the diagnosis was AML. The patient met the diagnostic criteria of two diseases at the same time, and thus he was confirmed as AML combined with T-LBL. AML chemotherapy regimens were given, and the patient achieved complete remission and disease-free survived.Conclusions:AML with LBL is extremely rare in children. The diagnosis mainly depends on MICM classification examination of bone marrow and pathological examination of lymph nodes. There is currently no standard treatment scheme, and the prognosis is extremely poor. AML chemotherapy followed by bridging hematopoietic stem cell transplantation is the best treatment option for these patients.

Objective To systematically evaluate the effects of prone position ventilation on newborn with respiratory distress syndrome.Methods We searched databases including PubMed,EMBASE,Cochrane Library,Web of Science,CBM,CNKI,Wanfang and VIP.We included all randomized controlled trials and randomized crossover trials of neonatal respiratory distress syndrome.Studies were selected according to inclusion and exclusion criteria,extracting data and assessing quality.Then RevMan 5.3 software was used to analyze the data.Results Ten studies included seven randomized controlled trials and three randomized crossover trials,and 500 patients were included.The results of meta-analysis showed that in prone position ventilation group SaO2[MD=2.41,95％CI(0.87,3.95),P=0.002],PaO2[MD=5.20,95％CI(3.04,7.36),P＜0.001],Pa2//FiO2[MD=24.40,95％CI(8.35,40.44),P=0.003],the risk of pneumothorax [RR =0.10,95％ CI (0.01,0.76),P=0.03] and intracranial hemorrhage [RR =0.41,95％ CI (0.20,0.83),P=0.01]and duration of mechanical ventilation [MD=-23.22,95％CI(-38.30,-8.14),P=0.003] compared with supine positiongroup had significantly statistical difference;however there was no significant difference in ventilator-associated pneumonia[RR=0.72,95％CI(0.48,1.09),P=0.12] between two groups.Conclusion Prone position ventilation is effective to improve SaO2,PaO2 and PaO2/FiO2,shorten duration of mechanical ventilation and reduce the risk of pneumothorax and intracranial hemorrhage in newborn with respiratory distress syndrome.While it could not effectively reduce incidence of ventilator-associated pneumonia.Due to the limitations of the quality of studies included,multi-centered randomized controlled trials with large sample size are needed in the future to evaluate the effects of prone position ventilation on neonatal respiratory distress syndrome.

Objective:To investigate whether the existence of thoracic artery blood supply in peripheral pulmonary lesions is the key factor affecting the accuracy of contrast-enhanced ultrasound in differentiating benign and malignant lesions.Methods:From June 2020 to December 2021, a total of 170 patients with peripheral pulmonary lesions were consecutively enrolled in Xi′an Chest Hospital, and all patients underwent conventional ultrasound and contrast-enhanced ultrasound(CEUS). Taking ΔAT(lesion-lung arrival time difference ) of 2.5 seconds as the cut-off point for differentiating benign and malignant lesions(ΔAT<2.5 s for benign, ΔAT≥2.5 s for malignant), and the final pathological results as the gold standard, these patiens were divided into correct classification group and wrong classification group, and the main influencing factors of wrong classification were analyzed.Results:Compared with the correct classification group, the proportion of thoracic artery blood supply in the wrong classification group was significantly higher ( P<0.001). After adjusting the dendritic venous reflux, thoracic artery blood supply was an independent influencing factor for CEUS misclassification ( OR=3.531, 95% CI=1.805-6.908, P<0.001). In the patients with thoracic artery blood supply, the sensitivity of the absence of dendritic venous reflux in judging malignant peripulmonary lesions was 75.0%, the specificity was 91.3%, and the area under the ROC curve (AUC) was 0.832 (95% CI=0.715-0.915, P<0.001), while the sensitivity, specificity and AUC of CEUS in judging malignant peripulmonary lesions were 68.7%, 67.4% and 0.659 (95% CI=0.528-0.775, P=0.006), and there was significant statistical difference in the AUC between them( P<0.001). In the group of patients without thoracic arterial blood supply, the sensitivity of the absence of dendritic venous reflux in judging malignant peripulmonary lesions was 82.8%, the specificity was 63.3%, and the AUC was 0.730 (95% CI=0.636-0.811, P<0.001), while the sensitivity, specificity and AUC of CEUS in judging malignant peripulmonary lesions were 62.1%, 81.0% and 0.684 (95% CI=0.587-0.770, P=0.003), and there was no significant difference in the AUC between them ( P=0.425). Conclusions:The presence of thoracic artery blood supply significantly decrease the diagnostic efficiency of CEUS in differentiating benign and malignant of peripheral pulmonary lesions. For peripheral pulmonary lesions with thoracic arterial blood supply, the diagnostic efficiency of dendritic venous reflux is better than CEUS, while for lesions without thoracic artery supply, the diagnostic efficiency of dendritic venous reflux is equivalent to CEUS.

Objective:To investigate the clinical characteristics, diagnosis and treatment and prognosis of children with leukemia secondary to malignant solid tumor.Methods:From January 2012 to January 2022, a total of 2 275 children under 15 years of age with malignant solid tumor were admitted to the First Affiliated Hospital of Zhengzhou University.Six children diagnosed with secondary leukemia after follow-up to August 1, 2022 were selected as the study objects.Their clinical data were retrospectively analyzed and the literature was reviewed.Results:(1)A total of 2 275 children with malignant solid tumors included 1 369 males and 906 females.There were 6 children with secondary leukemia, with an incidence rate of 0.26%, including 4 males and 2 females.The age of onset of solid tumor was 5.5(2.8, 9.7)years, and the age of secondary leukemia was(9.1±3.9)years, and the interval between them was(26.2±17.3)months.(2)Malignant solid tumor types: according to the time of secondary leukemia, there were hip malignant rhabdomyoma in 1 case, intracranial medulloblastoma in 2 cases, intracranial and pelvic malignant germinoma in 1 case respectively, and pancreatic blastoma in 1 case.Intracranial lesion biopsy was performed in 1 case, and tumor resection was performed in the other 5 cases.Three patients with intracranial tumors underwent local tumor bed, whole brain and spinal radiotherapy.All the 6 children received chemotherapy, and the main chemotherapy drugs were doxorubicin, vincristine, cyclophosphamide, platinum, ifosfamide, etoposide, bleomycin, temozolomide, etc.Complete remission was achieved in 3 cases, partial remission in 1 case, stable disease in 1 case, and disease progression in 1 case.(3)The secondary leukemia types were as follows: acute myeloid leukemia(AML)M5 in 3 cases, M1 in 1 case, M2 in 1 case, and acute B-lymphoblastic leukemia(B-ALL)in 1 case.All six cases refused hematopoietic stem cell transplantation(HSCT).One case with B-ALL gave up after receiving hydroxyurea and dexamethasone.Five cases with AML received chemotherapy according to the AML-2006 Protocol of Hematology Group of Pediatrics Society of Chinese Medical Association.The outcome of the disease was as follows: 2 cases died early, 4 cases achieved complete remission after 1 ~ 2 courses of chemotherapy, among which 2 cases did not continue treatment after 3 courses of chemotherapy due to pulmonary infection, deep mycosis, osteomyelitis, etc, and then recurred and died.By the end of follow-up, 2 cases survived and continued treatment, of which 1 case relapsed.After the diagnosis of secondary leukemia, the 1-year overall survival rate of the 6 cases was(33±26)%.Conclusion:Leukemia secondary to malignant solid tumors in children is rare and mostly occurs in older children.The pathogenesis is related to genotoxic injury caused by exposure to chemotherapy or radiotherapy, and the prognosis is unfavourable.HSCT after chemotherapy combined with immunotherapy is the best treatment strategy.

OBJECTIVETo explore significance of serum soluble CD163(sCD163) and soluble CD25(sCD25) in diagnosis and guiding treatment of children with hemophagocytic lymphohistiocytosis (HLH).

METHODData of 42 cases of children with HLH, 32 cases of non-HLH children with infection presented to First Affiliated Hospital of Zhengzhou University pediatric clinic and ward were collected from December 2013 to December 2014. Twenty-four healthy children were enrolled into a normal control group in the same period.Peripheral venous blood specimens (3 ml) were taken from the children with HLH after fasting before treatment, two weeks after treatment and eight weeks after treatment.Peripheral venous blood specimens (3 ml) were also taken from children of non-HLH infected group and normal control group after fasting at the initial visit. Serum sCD163 and sCD25 levels in the peripheral blood in three groups were determined by ELISA. According to cause of disease, children with HLH were divided into infection-related HLH, tumor-related HLH, primary HLH and others; relationship between serum sCD163 and sCD25 level and cause of disease was analyzed.

RESULTSerum sCD163 of HLH group ((6 094 ± 2 769) µg/L) and serum sCD163 of non-HLH infection group ((2 174 ± 950) µg/L) were significantly higher than that of normal control group ((777 ± 256) µg/L), F=71.396, P<0.05), and the differences among groups were statistically significant (P<0.05); serum sCD25 of HLH group ((41 963 ± 31 821) ng/L) and serum sCD25 of non-HLH infection group ((6 700 ± 4 105) ng/L) were significantly higher than that of normal control group ((2 440 ± 1 870) ng/L, F=37.513, P<0.05).There was no statistically significant difference between the non-HLH infection group with the normal control group (P>0.05), and the difference between the remaining groups was statistically significant (P<0.05). And serum sCD163 and sCD25 level of HLH group had a positive linear correlation, and Pearson correlation coefficient r=0.742 (t=7.000, P<0.05). The difference of serum sCD163 and sCD25 level among the different cause of disease in HLH group was significant (P<0.05).Pairwise comparison showed that serum sCD163 and sCD25 level of tumor-associated HLH group significantly increased as compared with infection-associated HLH group (P<0.05), but the difference was not statistically significant between the other groups (all P>0.05). Serum sCD163 and sCD25 level of HLH group before treatment, 2 weeks and 8 weeks after treatment showed a statistically significant tendency of decrease (P<0.05). Seen from the ROC curve, when sCD163 cut-off point was 2 359.08 µg/L, the diagnostic sensitivity was 83.3%, and specificity was 83.9%.When sCD25 cut-off point was 14 901.024 ng/L, the diagnosis sensitivity was 76.2%, and specificity was 98.2%.

CONCLUSIONSerum sCD163 and sCD25 levels may be used for diagnosis of HLH.Dynamically monitoring of serum sCD163 and sCD25 level can help to determine deterioration of HLH and guide treatment.

Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Case-Control Studies ; Child ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-2 Receptor alpha Subunit ; blood ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; therapy ; ROC Curve ; Receptors, Cell Surface ; blood ; Sensitivity and Specificity

Objective:The study aims to investigate the characteristic baseline information about genetic lineages, drug-resistance genes, virulence genes and evolutionary relationships of food-borne Listeria monocytogenes (Lm) isolates from Nanshan district of Shenzhen.Methods:The whole genomes of 46 Lm isolates during 2009-2019 were extracted and sequenced (Illumina PE-150, 100×). The CLC Genomics Workbench 12.0 was used to assemble and align Lm genomes, analyze their housekeeping genes, drug-resistance genes and virulence genes, and construct a k-mer phylogenetic tree.Results:After assembly, all genomes satisfied analytical conditions (contigs N50>20 kb). The medians of GC content, gene count and gene size were 38.3%, 5 960 and 2 952 608 bp, respectively. Based on the Lm genomic reference database, the local k-mer phylogenetic tree had 14 clusters of which the genetic distance was wide. The 46 Lm isolates were classified as Lineage 1 (21), Lineage 2 (23) and Lineage 3 (2). The most common ST type of Lineage 1 was ST87, followed by ST3, ST59, ST224 and ST429, whereas the major ST types of Lineage 2 included ST8 and ST9, the rest being ST121, ST155, ST199, ST204 and ST321. However, Lineage 3 only had ST299. The part of Lm strains carried five drug-resistance genes, such as fosX (17), tetM (6), dfrG (4), catB3 (1) and mefA (1). Furthermore, all strains possessed nine virulence genes, including flaA, iap, actA, hly, mpl, prfA, plcA, plcB and inlB. Nevertheless, six isolates and three of them respectively carried the mutant inlA and inlJ, and other two isolates lacked inlC.Conclusion:The food-borne Lm isolates from Nanshan district of Shenzhen presented genetic and evolutionary diversity. Noted that the drug-resistant strains, which also owned abundant virulence genes with specific functions, could lead to serious infections, particularly those isolates from raw poultry and Flammulina velutipes. It was implied that the local region was at risk due to Listeriosis by food. This study offered reference for prevention, control and treatment of Lm infection to the Greater Bay Area.

Objective:The study aims to investigate the characteristic baseline information about genetic lineages, drug-resistance genes, virulence genes and evolutionary relationships of food-borne Listeria monocytogenes (Lm) isolates from Nanshan district of Shenzhen.Methods:The whole genomes of 46 Lm isolates during 2009-2019 were extracted and sequenced (Illumina PE-150, 100×). The CLC Genomics Workbench 12.0 was used to assemble and align Lm genomes, analyze their housekeeping genes, drug-resistance genes and virulence genes, and construct a k-mer phylogenetic tree.Results:After assembly, all genomes satisfied analytical conditions (contigs N50>20 kb). The medians of GC content, gene count and gene size were 38.3%, 5 960 and 2 952 608 bp, respectively. Based on the Lm genomic reference database, the local k-mer phylogenetic tree had 14 clusters of which the genetic distance was wide. The 46 Lm isolates were classified as Lineage 1 (21), Lineage 2 (23) and Lineage 3 (2). The most common ST type of Lineage 1 was ST87, followed by ST3, ST59, ST224 and ST429, whereas the major ST types of Lineage 2 included ST8 and ST9, the rest being ST121, ST155, ST199, ST204 and ST321. However, Lineage 3 only had ST299. The part of Lm strains carried five drug-resistance genes, such as fosX (17), tetM (6), dfrG (4), catB3 (1) and mefA (1). Furthermore, all strains possessed nine virulence genes, including flaA, iap, actA, hly, mpl, prfA, plcA, plcB and inlB. Nevertheless, six isolates and three of them respectively carried the mutant inlA and inlJ, and other two isolates lacked inlC.Conclusion:The food-borne Lm isolates from Nanshan district of Shenzhen presented genetic and evolutionary diversity. Noted that the drug-resistant strains, which also owned abundant virulence genes with specific functions, could lead to serious infections, particularly those isolates from raw poultry and Flammulina velutipes. It was implied that the local region was at risk due to Listeriosis by food. This study offered reference for prevention, control and treatment of Lm infection to the Greater Bay Area.

OBJECTIVE To investigate the efficacy and adverse reaction of CD 19-targeted chimeric antigen receptor T cells （CAR-T）in the treatment of relapsed/refractory diffuse large B -cell lymphoma （R/R DLBCL ），so as to provide an evidence -based basis for more reasonable and efficient application of CAR -T. METHODS Retrieved from PubMed ，Embase，Cochrane， ClinicalTrials.gov，CNKI，Wanfang，VIP database ，the literature about CD 19 targeted CAR -T in the treatment of R/R DLBCL that were published from the inception to April 2022 were screened . Taking objective remission rate （ORR），complete remission rate （CRR）and incidence of adverse reactions as outcome indicators ，subgroup analysis was performed according to the costimulatory factor of CAR -T and the different types of research . R 4.1.2 software was used for meta -analysis，sensitivity analysis and publication bias analysis . RESULTS A total of 11 pieces of literature were screened ，involving 1 466 patients. The ORR of CD -19 targeted CAR -T cells in the treatment of R/R DLBCL was 72.1%（95% CI：62.3%-81.9%），the CRR was 50.8%（95% CI：41.1%- 60.5%），the incidence of cytokine release syndrome （CRS）was 77.5%（95% CI：65.6%-89.4%），the incidence of neurotoxicity was 41.4%（95% CI：26.8%-56.1%）. Results of subgroup analysis showed that the incidence of ORR ，CRR，CRS and neurotoxicity in costimulatory factor CD 28 subgroup were higher than those in 4-1BB subgroup . The incidence of ORR ，CRR，CRS and neurotoxicity in the observational experimental subgroup were higher than those in the intervention experimental subgroup . CONCLUSIONS CD19 targeted CAR -T has high ORR and CRR for R/R DLBCL ，as well as higher incidence of adverse reactions. Co-stimulatory factor CD 28 has higher ORR ，CRR， CRS incidence and neurotoxicity incidence than 4-1BB.

Objective:To analyze the relationship between the high sensitivity C-reactive protein (hs-CRP) and anxiety levels in patients hospitalized with cardiovascular-related diseases and hypertension.Methods:A total of 221 patients hospitalized with cardiovascular-related diseases in the Fuwai Hospital were selected by a voluntary sampling method from September to December 2021. Participants were divided into hypertensive and non-hypertensive groups ( n=119 and n=102) based on the diagnosis of hypertension in their inpatient medical records. Anxiety levels were assessed using the Zung Self-Rating Anxiety Scale, and the levels of serum hs-CRP were estimated by automatic immunoanalyzer. Multivariate logistic regression was used to analyze the relationship between hs-CRP and anxiety. Results:In the hypertensive group, the risk of anxiety in patients with abnormal hs-CRP (>3 mg/L) was 4.239 times (95% CI: 1.569-11.748, P=0.005) higher than those in normal hs-CRP (≤3 mg/L). In turn, compared with patients without anxiety, those with anxiety had 3.878 times greater probability of experiencing abnormal hs-CRP (95% CI: 1.495-10.062, P=0.005), while those with mild anxiety and moderate to severe anxiety had 4.525 times (95% CI: 1.392-14.714, P=0.012) and 3.286 times (95% CI: 0.911-11.357, P=0.070) greater odds of experiencing abnormal hs-CRP, respectively. No similar significant association was seen in the non-hypertensive group. Conclusion:There is an interrelationship between elevated hs-CRP and anxiety in hospitalized patients with cardiovascular-related diseases and hypertension.