Impact of angiogenic inhibition in the treatment of newly diagnosed and recurrent glioblastoma: a meta-analysis based on randomized controlled trials.

OBJECTIVE: Glioblastoma (GBM) is the most common and aggressive primary malignant tumor of the central nervous system in adults with high recurrence and mortality rates. Although radiotherapy and temozolomide have become the standard therapeutic regimen for GBM as adjuvant chemoradiotherapy after surgical resection, clinical outcomes remain suboptimal. In recent years, targeted antiangiogenic therapy has attracted considerable attention, but its therapeutic efficacy and safety are still controversial. MATERIALS AND METHODS: Randomized controlled trials (RCTs) of chemoradiotherapy with or without bevacizumab for the treatment of glioblastoma were collected by searching on the Pubmed, Embase, Cochrane, Ovid, Scopus, Web of Science, and Google Scholar databases from the date of database establishment to February 2022. Meta-analysis was performed using RevMan 5.3 software after two investigators independently screened the literature, extracted data, and assessed the risk bias of included studies. RESULTS: A total of 7 RCTs were included. The meta-analysis showed that bevacizumab in combination with chemoradiotherapy was superior to chemoradiotherapy alone in terms of progression-free survival (PFS), with a statistically significant difference. Interestingly, bevacizumab in combination with chemoradiotherapy improved PFS more significantly in recurrent glioblastoma than in newly diagnosed glioblastoma. However, for overall survival (OS), the combination of bevacizumab with chemoradiotherapy was similar to chemoradiotherapy alone, which was not significantly different. With regard to safety, the incidence of most adverse events was higher in the combination of bevacizumab and chemoradiotherapy than in chemoradiotherapy alone, especially in terms of hematologic adverse events. CONCLUSIONS: Current evidence suggests that angiogenesis inhibitor-containing chemoradiotherapy regimens are preferentially recommended for patients with recurrent glioblastoma to prolong their progression-free survival, provided that safety is acceptable, but this does not confer a significant benefit on overall patient survival.

Docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer: a meta-analysis.

OBJECTIVE: Although bevacizumab and trastuzumab have been widely added to the standard regimen for metastatic breast cancer, the clinical outcomes remain controversial. The purpose of this study was to conduct meta-analysis to verify the clinical efficacy and safety of docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: All available literature of clinical trials about docetaxel, bevacizumab, trastuzumab and metastatic breast cancer was pooled from PubMed, Embase and Cochrane library database. The meta-analysis combined the progression free survival (PFS), overall response rate (ORR) and incidence of all grades adverse events in MBC patients. RESULTS: Seven clinical trials were included by two reviewers. Docetaxel and bevacizumab with trastuzumab show the pooled PFS was 16.53 months (95% CI: 13.95-19.11 months), the pooled ORR was 0.75 (95% CI: 0.69-0.80) in HER2-positive MBC patients. Docetaxel and bevacizumab show that the pooled PFS was 8.49 months (95% CI: 7.80-9.18 months), the pooled ORR was 0.51(95% CI: 0.47-0.55) in HER2-negative MBC patients. CONCLUSIONS: Both for patients with HER2-positive and negative metastatic breast cancer, docetaxel and bevacizumab with or without trastuzumab as first-line treatment resulted in long survival, especially in terms of progression-free survival. Although the overall response rates are also significantly improved, it is still controversial based on the current evidence.

[Analysis of immunity markers related to nosocomial infection in children with sepsis].

Objective: To investigate the immunity markers related to nosocomial infection in children with sepsis. Methods: A retrospective study including 155 cases diagnosed as sepsis from September 2015 to June 2020 in children's intensive care unit (PICU) of Shanghai Children's Medical Center was conducted. According to the presence of nosocomial infection occurred in PICU, septic children were divided into two groups: no nosocomial infection and nosocomial infection group. The differences about helper T-cells 1 and 2 cytokines, T cells subgroup absolute count, the proportion of CD14+ human leukocyte antigen DR (CD14+HLA-DR), the proportion of regulatory T cells, pediatric risk of mortality Ⅲ (PRISM-Ⅲ), the treatment and outcome between the two groups were compared. Through propensity score matching (PSM), the disease severity and treatment of the two groups were matched to analyze the differences between the above indicators. Chi-square test or U test was used for comparison between groups. Receiver operating characteristic (ROC) curve was used to predict the occurrence of nosocomial infection. Results: There were 104 cases in no nosocomial infection group and 51 cases in nosocomial infection group. The first PICU-acquired infections occurred at (12±7) days after PICU admission. The most common PICU-acquired infections were pneumonia (26 cases, 51.0%) and bloodstream infections (15 cases, 29.4%). PRISM-Ⅲ of nosocomial infection group was significantly higher than that in no nosocomial infection group (8 (0-31) vs. 4 (0-17), Z=3 913.00, P<0.01).The proportion of using vasoactive drugs and invasive mechanical ventilation of nosocomial infection group was significantly higher (35.3% (18/51) vs. 10.6% (11/104), χ²=13.77, P<0.01; 86.3% (44/51) vs. 38.5% (40/104), χ²=31.51, P<0.01).The PICU length of stay of nosocomial infection group was significantly longer (20 (3-94) vs.7 (2-41) days, Z=4 585.50, P<0.01). The mortality of the nosocomial infection group was significantly higher than that of the group without nosocomial infection (29.4% (15/51) vs. 6.7% (7/104), χ²=14.45, P<0.01). Interleukin-6 and interleukin-10 of the nosocomial infection group were significantly higher than that in no nosocomial infection group (37.83 (2.23-7 209.99) vs. 13.45 (0.80~50 580.64) ng/L, Z=3 390.50, P=0.01; 10.42 (1.11-6 052.21) vs.4.10 (0.16-409.28) ng/L, Z=3 212.00, P=0.03). CD4+/CD8+ and the percentage of CD14+HLA-DR were significantly lower in the nosocomial infection group compared with the no nosocomial infection group (1.16 (0.44-4.96) vs. 1.61 (0.15-6.37), Z=1 955.00, P=0.01; 0.48 (0.08-0.99) vs. 0.67 (0.09-0.98), Z=1 915.50, P<0.01). After PSM, the percentage of CD14+HLA-DR of nosocomial infection group was significantly lower than that in no nosocomial infection group (0.44 (0.08-0.99) vs. 0.64 (0.09-0.98), Z=758.00, P=0.02). The ROC curve analysis of the percentage of CD14+HLA-DR in predicting nosocomial infection showed that the area under the curve was 0.642, the cut-off value was 0.39, and the 95%CI was 0.528-0.755. Conclusion: The level of the percentage of CD14+HLA-DR maybe is related to the occurrence of nosocomial infection in children with sepsis.

[Application of apparent diffusion coefficient histogram in moderate to severe neonatal hypoxic-ischemic encephalopathy].

Objective: To investigate the diagnostic value of apparent diffusion coefficient (ADC) histogram in quantifying moderate to severe neonatal hypoxic-ischemic encephalopathy (HIE). Methods: A total of 49 children with moderate to severe HIE admitted to the Children's Hospital Affiliated to Nanjing Medical University from July 2015 to September 2018 were retrospectively analyzed. Cranial magnetic resonance imaging (MRI) data of 31 full-term neonates without neurological symptoms and signs who visited the hospital during the same period were recruited as the control group. ImgJ software was used to delineate the whole brain area at the thalamus/basal ganglia level as the area of interest, and MRIcron software was used to obtain ADC histogram parameters. The differences of ADC histogram parameters between HIE group and control group were compared. The correlation between ADC histogram parameters and neonatal neurobehavioral neurological assessment (NBNA) in HIE group was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of each parameter. Results: The mean value, minimum value, maximum value, mode-value, variance, heterogeneity and 10%-90% ADC values of HIE group were all greater than those of the control group(634±65,310±36,1 683±18,711±87,66 928±921,5 907±204,477±50,513±53,542±56,568±59,591±61,625±92,661±97,709±105,811±119),the differences were statistically significant(all P<0.05), while mode-count of HIE group was smaller than that of the control group(272±22 to 395±83), and the difference was statistically significant (t=2.996,P<0.05). All the above parameters with statistical differences were correlated with NBNA score, among which mode-count was negatively correlated with NBNA score(r=-0.369,P<0.05), and the rest were positively correlated(all P<0.05). The area under the ROC curve (AUC) of variance had the highest diagnostic efficiency (0.881), followed by 90% ADC value and ADC maximum value. Conclusion: ADC histogram is helpful for the diagnosis of HIE, objectively and quantitatively reflecting the diffusion information of brain, and assessing the severity of HIE.

[Identification and evaluation on methods with upstream flank sequences of CRISPR1, regarding Escherichia coli and Shigella].

Objective: To analyze the effect of the identification and evaluation of Escherichia (E.) coli and Shigella, based on the upstream flanking sequences of CRISPR1. Methods: Both CRISPR and cas sequences were obtained through the BLAST with repeating sequences against the publicly complete genome in GenBank that related to E. coli and Shigella. Clustal X was used to perform multi-sequences alignment of the flanking sequences. PCR method was used to amplify the upstream flanking sequences of CRISPR1 in order to appraise the effect of identification and evaluation of upstream flanking sequences on E. coli and Shigella, which were based on the upstream flanking sequences of CRISPR1. Results: The results showed that 73.4% of the strains containing the I-E CRISPR/Cas that belonged to the phylogroups A, B1, D while 8.4% strains carried the I-F CRISPR/Cas. Another 17.2% of the strains owned CRISPR3-4 (non-CRISPR/Cas) only belonged to the phylogroups B2. All the Shigella strains carried I-E CRISPR/Cas. More than 99% of similarity the CRISPR1 upstream-flanking sequences was seen in E. coli (except B2) and Shigella and E. coli (B2). Both sensitivity and specificity were greater than 91% after PCR amplification in the region to identify the E.coli and Shigella. Conclusion: The upstream of CRISPR1 could achieve a preliminary identification effect on E.coli and Shigella.

[Association between phage-mediated shiga toxin and molecular distribution of CRISPR in Escherichia coli O26 ∶ H11 or NM].

Objective: To investigate the association between phage-mediated shiga toxin and molecular distribution of CRISPR in Escherichia (E.) coli O26∶H11 or NM. Methods: A total of 135 E. coli O26 ∶ H11 or NM strains were collected from NCBI database. Software CRT and CRISPR Finder were used to extract CRISPR and Excel was used to assign the spacer of unique number and type CRISPR. And the relationship between CRISPR and stx phage was analyzed. Results: All the 135 E. coli O26 ∶ H11 or NM strains had the CRISPR. For CRISPR1, CRISPR2.1, CRISPR2.2 and CRISPR3-4, 19, 22, 1 and 1 subtypes were found, respectively. According to the four CRISPR sites, the strains could be divided into 40 subtypes. Stx-phage was only observed in the group C of CRISPR. Compared with E. coli of stx-phage negative, E. coli with stx-phage harbored more spacers. Conclusions: CRISPR loci was extensively existed in E. coli O26∶H11 or NM, and many subtypes were found in these strains. The presence of stx-phage was related to the molecular distribution of CRISPR in E. coli O26∶H11 or NM. CRISPR might be a valuable biomarker to identify strains with high virulent potential.

[Changes of resistant phenotype and CRISPR/Cas system of four Shigella strains passaged for 90 times without antibiotics].

Objective: To explore the stability of resistant phenotypes and changes of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) gene system on four Shigella strains in the absence of antibiotics. Methods: Four clinical isolated Shigella strains that resistant to different antibiotics were consecutive passaged for 90 times without antibiotics. Agar dilution method was used to determine the minimum inhibitory concentration of Shigella strains. After sequence analysis with PCR, CRISPR Finder and Clustal X 2.1 were applied to identify the changes of CRISPR loci in the Shigella strains. Results: After the consecutive transfer of 90 generations, sensitivity to certain antibiotics of four Shigella strains with different drug resistant spectrums increased. Mel-sf1998024/zz resistance to ampicillin, cephalexin, cefotaxime, chloramphenicol decreased, mel-s2014026/sx resistance to norfloxacin, trimethoprim decreased, mel-sf2004004/sx drug resistance to ampicillin, cefuroxime, cefotaxime, chloramphenicol, trimethoprim decreased and mel-sf2013004/bj resistance to chloramphenicol decreased. The spacer of which matched gene codes Cas and its upstream repeat in 3'end of CRISPR3 got lost in mel-sf1998024/zz and mel-sf2013004/bj. Conclusions:Shigella strains could reduce or lose their resistance to some antibiotics after consecutive transfers, without the interference of antibiotics. CRISPR3 locus had dynamic spacers in Shigella strains while CRISPR3 locus and cas genes might have been co-evolved.

[A surveillance study on CRISPR/Cas molecular biomarker in Escherichia coli].

OBJECTIVE: A new method related to molecular biomarker with CRISPR/Cas (clustered regularly interspaced short palindromic repeats-cas) in Escherichia (E.) coli was developed and used for surveillance programs. METHODS: CRISPR/Cas sequence that containing 135 strains with complete sequence and 203 strains with whole genome shotgun sequence of E. coli in GenBank by BLAST and 361 strains of E. coli (including 38 strains of E. coli O157∶H7) in laboratory were identified by PCR and analyzed with the CRISPR Finder. Spacers were compared with DANMAN and the phylogenetic trees of cas gene were constructed under Clustal Ⅹ and Mega 5.1. RESULTS: With new perspective, a descriptive method was developed targeting on the position of CRISPR/cas in E. coli. The CRISPR1 was detected in 77.04%, 100.00% and 75.62% and the CRISPR2 was detected in 74.81%, 100.00% and 92.24% and the CRISPR3 and CRISPR4 were detected in 11.85%, 0 and 1.39% for 135 strains with complete sequence, 203 strains with whole genome shotgun sequence and 361 strains in the laboratory, respectively. One strain downloaded in GenBank with whole genome sequencing and 2 strains in the our laboratory were identified that containing four CRISPR locus. The other E. coli strain was with insertion sequence in downstream of the non-cas CRISPR1. The unique CRISPR was found in 8 strains of O55∶H7, in 180 strains of O157∶H7, in 8 strains of O157∶HNM, in 40 strains of O104∶H4, in 4 strains of O145∶H28, in all the 699 E. coli strains. The phylogenetic tree could be divided into two groups-cas with type I-E or type I-F. CONCLUSIONS: CRISPR/Cas might be used as a valuable molecular biomarker in epidemiological surveillance studies to identify the high virulent strains or new strains of E. coli. Phage night be related to the missing or obtaining of spacers.

Y-STR INRA189 polymorphisms in Chinese yak breeds.

To further explore Y-STR INRA189 polymorphisms in the yak, and to determine the genetic differences among yak breeds, genotyping analysis of INRA189 in 102 male yak individuals from three yak breeds in Qinghai Province of China was performed. Genotyping revealed the presence of four alleles, with sizes of 149, 155, 157, and 159 bp, respectively. Of these, the 157-bp allele, which was found with the highest frequency in the three yak breeds, was the dominant allele. Interestingly, the 149-bp allele was only detected in the Gaoyuan breed, and the 159-bp allele was only found in the Huanhu and Datong breeds. Only the 157- and 155-bp alleles were found in all three yak breeds. Taking the three yak breeds as a single population, the frequency of these four alleles was 0.0294, 0.0686, 0.8628, and 0.0392, respectively. The average polymorphism information content in the three yak breeds was 0.2379, indicating that the INRA189 was a low polymorphic Y-STR marker in yak.

rDNA ITS sequences among morphotypes of Keratell cochlearis, Keratell quadrata and Brachionus forficula (Rotifera).

Morphological variation in rotifers is affected by environmental conditions, making it hard to identify some rotifer taxa. We examined the rDNA ITS sequences of 10 unspined (KCU1-KCU10) and 17 spined (KCS1-KCS17) Keratell cochlearis clones, 26 two-spined (KQT1-KQT26), 18 single-spined (KQS1-KQS18) and 9 unspined (KQU1-KQU9) K. quadrata clones, and 17 long-spined (BL1-BL17) and 11 short-spined (BS1-BS11) Brachionus forficula clones collected from Lake Tingtang in Wuhu city, China. Molecular phylogenetic trees were constructed by neighbor-joining, maximum-likelihood, maximum parsimony, and Bayesian inference methods using B. calyciflorus as an outgroup. The K. cochlearis clones included 20 haplotypes, the K. quadrata clones included 37 haplotypes, and the B. forficula clones included 25 haplotypes. Different morphotypes of each rotifer species had shared haplotypes. Sequence divergences were 0.1-8.9% among different K. cochlearis haplotypes, and 8.1-8.9% between KCHAP1 (KCU1 and KCU10), KCU3, KCU4 and KCU6, and the other haplotypes. Sequence divergences were 0.1-14.5% among different K. quadrata haplotypes, and 11.9-14.5% between KQS17 and the other haplotypes. Sequence divergences were 0.1-11.7% among different B. forficula haplotypes, 11.0-11.7% between BL15 and the other haplotypes, 9.3-10.1% between BS3 and the other haplotypes, and 11.7% between BL15 and BS3. The four phylogenetic trees all supported that KCHAP1, KCU3, KCU4, KCU6 and the other 16 haplotypes among the 20 K. cochlearis haplotypes, KQS17 and the other 36 haplotypes among the 37 K. quadrata haplotypes, and BL15, BS3 and the other 23 haplotypes among the 25 B. forficula haplotypes all belonged to their own isolated clades. The morphological variation of the three rotifer species was attributed mainly to phenotypic plasticity.

In vitro degradation and cytotoxicity of Mg/Ca composites produced by powder metallurgy.

Mg/Ca (1 wt.%, 5 wt.%, 10 wt.% Ca) composites were prepared from pure magnesium and calcium powders using the powder metallurgy method, aiming to enlarge the addition of Ca content without the formation of Mg(2)Ca. The microstructures, mechanical properties and cytotoxicities of Mg/Ca composite samples were investigated. The corrosion of Mg/Ca composites in Dulbecco's modified Eagle's medium (DMEM) for various immersion intervals was studied by electrochemical impedance spectroscopy measurements and environmental scanning electron microscope, with the concentrations of released Mg and Ca ions in DMEM for various immersion time intervals being measured. It was shown that the main constitutional phases were Mg and Ca, which were uniformly distributed in the Mg matrix. The ultimate tensile strength (UTS) and elongation of experimental composites decreased with increasing Ca content, and the UTS of Mg/1Ca composite was comparable with that of as-extruded Mg-1Ca alloy. The corrosion potential increased with increasing Ca content, whereas the current density and the impedance decreased. It was found that the protective surface film formed quickly at the initial immersion stage. With increasing immersion time, the surface film became compact, and the corrosion rate of Mg/Ca composites slowed down. The surface film consisted mainly of CaCO(3), MgCO(3)x3H(2)O, HA and Mg(OH)(2) after 72 h immersion in DMEM. Mg/1Ca and Mg/5Ca composite extracts had no significant toxicity (p>0.05) to L-929 cells, whereas Mg/10Ca composite extract induced approximately 40% reduced cell viability.

Effect of aldrin on life history characteristics of rotifer Brachionus calyciflorus pallas.

The organochlorine insecticide aldrin is commonly used in intensive agriculture, and demonstrates estrogenic activity. Rotifers such as Brachionus calyciflorus are favored test animals in aquatic toxicology because of their more sensitivity to most toxicants. In the tested concentration range of 0.04-1.28 mg/L, aldrin shortened significantly the durations of embryonic development. Lower concentrations of aldrin had an intriguing effect on the reproduction of the rotifers and are beneficial to their survival. Different endpoints of both development and reproduction had different sensitivity to aldrin. The reproductive endpoint of the rotifers is more sensitive to aldrin than the developmental endpoint.