Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Anterior cruciate ligament (ACL) injury of knee is a common sports injury.The hypofunc-tion of the knee joint appears after ACL injury,which seriously affects the overall stability,coordination and balance ability of the knee joint,meanwhile also increases the risk of ACL injury again.Proprioception training can not only enhance the balance ability of the knee joint,but also enhance the control ability of the knee joint.This article reviews the changes of proprioception after ACL injury and the related contents of proprioception rehabilitation after ACL injury in order to provide reference for further improving the functional recovery of the patients with ACL injury.

Objective:To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

Objective:To understand the utilization situation of community health service institutions, the awareness of basic public health items and the degree of satisfaction of residents in Guangzhou City, so as to provide direction and reference for improving the quality of community health service in Guangzhou City.Methods:In December 2020, 1 050 residents in a district of Guangzhou City were selected by multi-stage random sampling method to fill out the questionnaire. Single factor analysis was used for Pearson chi-square test, and binary logistic regression analysis was used for multiple-factor analysis.Results:A total of 1 092 questionnaires were sent out and 1 050 were valid, with an effective rate of 96.2%. The average times of seeing a doctor or receiving other health services in community health service center in the past year were (4.60±4.10). The total awareness rate of basic public health services was 91.6%(962/1 050), and the total awareness rate of free public health services was 89.5% (940/1 050). The total scores of residents' satisfaction with community health service institutions were (4.61±0.75) points, among which the basic medical service scored the highest, and the institution facilities, system and basic information scored the lowest. Single factor analysis showed that 10 factors, such as type of medical insurance, preferred medical institution, walking time to community center and medical service time, were the influencing factors of residents' overall satisfaction. Multiple-factor analysis found that institutions and facilities, systems and basic conditions, basic medical services, medical expenses, the type of first-visited hospital were the four influencing factors of residents' overall satisfaction ( OR=21.294, 109.013, 18.203 and 20.989, respectively). Conclusion:The residents have a good utilization of community health services, and they have good awareness of public health service projects, but the residents' satisfaction with community health services still needs to be improved, especially in the aspects of facilities, equipment and service efficiency of medical staff.

Objective:To analyze the feasibility and clinical efficacy of reperfusion-expanding-thrombectomy-stenting (RETS) technique in the endovascular treatment of acute carotid artery tandem lesion.Methods:The general clinical data of 88 patients with carotid artery tandem lesion who received emergency endovascular treatment from January 2018 to December 2020 in Department of Neurology, Linyi People′s Hospital were reviewed, the Modified Rankin Scale (mRS) was used as the evaluation standard for the prognosis of patients at 90 days after endovascular treatment, and the clinical data were analyzed, including the recanalization (modified thrombolysis in cerebral infarction ≥2b), perioperative complications and 90-day prognosis, and good prognosis was defined as a mRS score of 0-2.Results:A total of 88 patients with tandem carotid artery disease were included,48 of whom were treated with RETS technique, 40 were treated with anterograde approach. Compared with antegrade recanalization, RETS technique had significant differences in the time from puncture to recanalization [(72.06±17.29) min vs (98.88±26.09) min, t=-5.56, P<0.001] and the primary recanalization rate [35/48(73.0%) vs 21/40(52.5%),χ2=3.93 ,P=0.047], with statistically significant difference. There was no significant difference in clinical prognosis and surgical complications between the two methods (all P>0.05). Conclusions:RETS technique can shorten the operation time and increase the primary recanalization rate. RETS technique is safe and feasible for the treatment of carotid tandem lesions.

Objective:To explore the abnormalities of efficiency in resting state functional brain network in patients with paranoid schizophrenia and the correlations between efficiencies and clinical symptoms.Methods:A total of 73 patients with schizophrenia (SZ group) met with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) criteria for schizophrenia and 70 healthy controls (HC group) were included .All subjects were checked by using functional magnetic resonance imaging (fMRI), and positive and negative syndrome scale(PANSS) were used to assess the symptoms.Abnormalities of global and local efficiency of brain regions in brain functional network were analyzed by graph theory.Pearson correlation was used to analyze the correlation between the abnormal global efficiency and local efficiency of brain regions of SZ group and PANSS.SPSS 20.0 software was used for dependent-sample t-test, ANOVA test and Pearson correlation analysis. Results:Compared with the HC group, SZ group showed increased global efficiency in bilateral thalamus(left: 0.26±0.06, 0.28±0.04, t=2.03, P=0.044.right: 0.26±0.06, 0.28±0.05, t=2.08, P=0.040), right orbital part of middle frontal gyrus(0.21±0.04, 0.23±0.05, t=2.25, P=0.026), cerebellar lobule Ⅸ(0.19±0.06, 0.21±0.05, t=2.56, P=0.011) and vermis Ⅲ(0.15±0.08, 0.19±0.07, t=3.27, P=0.001), while decreased global efficiency in bilateral parahippocampal gyrus(left: 0.25±0.05, 0.22±0.05, t=-3.34, P=0.001.right: 0.27±0.04, 0.23±0.05, t=-4.96, P=0.000), superior occipital gyrus(left: 0.27±0.03, 0.26±0.03, t=-2.70, P=0.008.right: 0.27±0.02, 0.26±0.03, t=-2.73, P=0.007), superior parietal gyrus(left: 0.27±0.03, 0.26±0.05, t=-2.63, P=0.010.right: 0.27±0.03, 0.25±0.05, t=-2.76, P=0.007), paracentral lobule(left: 0.28±0.03, 0.26±0.07, t=-2.47, P=0.015.right: 0.28±0.04, 0.25±0.07, t=-3.06, P=0.003), left precental gyrus(0.28±0.04, 0.27±0.04, t=-1.98, P=0.049), left cuneus(0.26±0.04, 0.25±0.04, t=-2.08, P=0.039), left lingual gyrus(0.29±0.03, 0.28±0.03, t=-2.28, P=0.024), left middle occipital gyrus(0.29±0.03, 0.28±0.03; t=-2.74, P=0.007), left middle temporal gyrus(0.28±0.03, 0.26±0.03, t=-2.73, P=0.007), temporal pole in left middle temporal gyrus(0.20±0.06, 0.18±0.06, t=-2.59, P=0.011) and right hippocampus(0.27±0.04, 0.26±0.06, t=-2.05, P=0.042).Compared with the HC group, SZ group showed increased local efficiency in bilateral caudate nucleus(left: 0.33±0.06, 0.35±0.05, t=2.54, P=0.012.right: 0.33±0.07, 0.35±0.04, t=2.77, P=0.007) and left superior occipital gyrus(0.39±0.03, 0.40±0.02, t=2.17, P=0.031), while decreased local efficiency in bilateral parahippocampal gyrus(left: 0.35±0.04, 0.32±0.07, t=-3.16, P=0.002.right: 0.34±0.04, 0.32±0.07, t=-2.91, P=0.004), left supplementary motor area(0.36±0.02, 0.35±0.05, t=-2.01, P=0.047), left inferior parietal but supramarginal and angular gyrus(0.35±0.03, 0.34±0.05, t=-2.65, P=0.009), left cerebellar crus Ⅱ(0.37±0.03, 0.36±0.04, t=-2.01, P=0.046), lobule ⅦB(0.37±0.03, 0.35±0.07, t=-1.98, P=0.049), right posterior cingulate gyrus(0.36±0.04, 0.34±0.07, t=-2.07, P=0.041), right superior parietal gyrus(0.37±0.03, 0.36±0.05, t=-2.19, P=0.031), right precuneus(0.36±0.02, 0.35±0.04, t=-2.36, P=0.020), right paracentral lobule(0.37±0.02, 0.36±0.06, t=-2.07, P=0.041) and right temporal pole in middle temporal gyrus(0.33±0.08, 0.30±0.09, t=-2.09, P=0.038).The global efficiency of bilateral paracentral lobule and left temporal pole in middle temporal gyrus in SZ group were negatively correlated with the negative scale scores( r=-0.25, -0.25, -0.26, all P<0.05).The global efficiency of right hippocampus in SZ group was positively correlated with total scores of PANSS( r=0.23, P=0.049).The global efficiency of left middle temporal gyrus in SZ group was negatively correlated with total scores of PANSS( r=-0.23, P=0.049).The local efficiency of right paracentral lobule in SZ group was negatively correlated with the positive scale scores( r=-0.24, P=0.038). Conclusion:The brain networks of patients with first-episode paranoid schizophrenia may have regional dysfunction in the transmission efficiency and fault-tolerant ability of resting state brain functional network, and the abnormalities of efficiency may be associated with the severity of psychiatric symptoms in several brain regions.

Objective:To explore the relationship between rs671 (ALDH2), rs1229984 (ADH1B), RS141973904 (ADH1C), RS1799971 (OPRM1), rs1997794 (PDYN) polymorphism and individual's alcohol subjective response and drinking behavior.Methods:From January to December 2018, patients with alcohol dependence who were hospitalized in the First Affiliated Hospital of Xinjiang Medical University and Xinjiang mental health center and met the DSM-IV were selected (alcohol dependence group, n=100). Alcohol dependence patients and normal healthy subjects (control group, n=100) completed general demographic questionnaire, including drinking behavior such as the frequency of drinking each week and the maximum alcohol consumption at one drink, and informed consent, then were extracted of venous blood for DNA test.After that, alcoholics completed the alcohol challenge test.Biphasic alcohol effect scale(BAES) and drug effect questionnaire (DEQ) were completed before drinking and after drinking 30, 60, 120, 180 minutes respectively.Hardy-Weinberg equilibrium for genetic linkage analysis was calculated by utility program.Pearson Chi-square test was used to analyze the odds ratio(OR) value, and the chi-square test of repeated measured variables were used to analyze the variation trend of individual subjective response to alcohol after drinking. Results:rs671 allele A was associated with alcohol dependence risk (χ 2=23.97, P<0.01, OR=7.11, 95% CI=2.93~17.30), and for rs1229984 polymorphism the dominant genetic model " T/T-C/T" was taken as the best fitting model ( P<0.01, OR=0.16, 95% CI=0.08-0.32), which was a protective factor for alcohol dependence.Alcoholics with TT genotype in rs1229984 had lower maximum alcohol consumption ( F=4.86, P=0.01) and weekly alcohol consumption ( F=4.51, P=0.01) than those with CC and CT genotype.The maximum alcohol consumption ( F=20.28, P<0.01) and weekly alcohol consumption ( F=12.46, P<0.01) of individuals with GG and GA genotype in rs1799971 were higher than those with AA genotype.The AA genotype of rs1799971 showed lower stimulative effect ( F=7.99, P=0.01), higher sedative effect ( F=57.04, P<0.01), and lower " like" ( F=13.38, P<0.01) and " more" effect ( F=26.37, P<0.01) than that with GG and GA genotype. Conclusion:rs671 and rs1229984 are more closely related to individual drinking behavior and volume of alcohol consumption.rs1799971 is not only related to individual drinking behavior, but also has a more closed relationship with subjective response to alcohol.

Effective utilization of xylose is a basis for economic production of biofuels or chemicals from lignocellulose biomass. Over the past 30 years, through metabolic engineering, evolutionary engineering and other strategies, the metabolic capacity of xylose of the traditional ethanol-producing microorganism Saccharomyces cerevisiae has been significantly improved. In recent years, the reported results showed that the transcriptome and metabolome profiles between xylose and glucose metabolism existed significant difference in recombinant yeast strains. Compared with glucose, the overall process of xylose metabolism exhibits Crabtree-negative characteristics, including the limited glycolytic pathway activity, which reduces the metabolic flux of pyruvate to ethanol, and the enhanced cytosolic acetyl-CoA synthesis and respiratory energy metabolism. These traits are helpful to achieve efficient synthesis of downstream products using pyruvate or acetyl-CoA as precursors. This review provides a detailed overview on the modification and optimization of xylose metabolic pathways in S. cerevisiae, the characteristics of xylose metabolism, and the construction of cell factories for production of chemicals using xylose as a carbon source. Meanwhile, the existed difficulties and challenges, and future studies on biosynthesis of bulk chemicals using xylose as an important carbon source are proposed.
Biofuels ; Ethanol ; Fermentation ; Metabolic Engineering ; Saccharomyces cerevisiae/genetics* ; Xylose