BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

In order to learn from the advanced experience of postgraduate education in foreign first-class universities, Harvard University, Johns Hopkins University and London School of Hygiene and Tropical Medicine were selected as the objects in this study to analyze and compare the advantages and characteristics of their postgraduate training model, curriculum setting and teaching resources, thereby providing suggestions for the reform and development in the cultivation of master of public health and preventive medicine in China.

OBJECTIVE To systema tically evaluate the efficacy and safety of blinatumomab for acute lymphoblastic leukemia （ALL）in order to provide evidence-based reference for clinical use. METHODS Retrieved from PubMed ，Embase，Web of Science，the Cochrane Library ，CNKI，Wanfang database and CBM during the inception to February 3，2022，randomized controlled trials （RCTs）and cohort studies of blinatumomab （experimental group ） versus conventional chemotherapy （control group ）in the treatment of ALL were collected. After literature screening and data extraction ，the quality of RCTs was evaluated by the risk bias evaluation tool recommended by Cochrane handbook 5.1.0，and the quality of cohort studies was evaluated by the Newcastle-Ottawa scale （NOS）. Meta-analysis was performed by RevMan 5.4 software. GRADE grading system was used to evaluate the evidence quality of outcomes. The publication bias was analyzed by inverted funnel plot. RESULTS A total of 8 studies were included ，involving 3 RCTs and 5 cohort studies ，with a total of 2 841 patients. Results of Meta-analysis showed that the overall survival rate more than one year [RR ＝1.30，95％CI（1.14，1.48），P＜0.000 1]，relapse-free survival rate [RR ＝1.78，95％CI（1.50，2.12），P＜0.000 01]，complete remission rate [RR ＝1.42，95％CI（1.11，1.82），P＝0.006]，the incidence of tremor [RR ＝16.98，95％CI（2.17，133.12），P＝0.007]，and the incidence of cytokine release syndrome [RR ＝14.11， 95％CI（3.43，58.01），P＝0.000 2] in trial group were all significantly higher than control group ，but there was no statistical significance in the incidence of headache between two groups [RR ＝1.31，95％CI（0.66，2.59），P＝0.44]. The incidence of adverse events with grade more than or equal to 3，infection，stomatitis，thrombocytopenia，febrile neutropenia ，anorexia， constipation，diarrhea，abdominal pain ，hypokalemia in trial group were significantly lower than control group （P＜0.05）. The incidence of cough ，rash and hypogamma globulinemia and fever in the trial group were significantly higher than control group （P＜0.05）. There was no statistical significance in the total incidence of adverse events ，sepsis，anemia，leucopenia，neutropenia， lymphopenia，nausea，vomiting，hyperglycemia，hypotension，hypertension，elevated transaminase or epistaxis between two groups（P＞0.05）. Results of subgroup analysis by study type showed that the overall survival rate ，relapse-free survival rate and complete response rate （except for cohort studies ）of patients in trial group were significantly higher than control group in both RCTs and cohort studies （P＜0.05）. The results of GRADE evaluation showed that the overall quality of index evidence included in this study was low. There was little possibility of publication bias in this study based on the publication bias analysis. CONCLUSIONS Blinatumomab is effective in the treatment of ALL ，with low incidence of infection and adverse events of digestive system ，but high incidence of tremor ，cough，rash，fever，hypoproglobulinemia and cytokine release syndrome. The evidence quality of the indicators included in this study is generally low .

Objective:To analyze the situation of articles published in Journal of Leukemia & Lymphoma and provide reference for the development of the journal and better service to readers and authors. Methods:All articles published in Journal of Leukemia & Lymphoma from January 2019 to December 2021 were searched on the official website of the journal (www.bxblbl.com.cn) and the full-text database of Chinese medical journals (www.yiigle.com), and the statistical analysis of the articles published in the journal was performed using bibliometric methods and Excel software. Website readings and downloads were recorded based on data from the Chinese medical journal network publishing platform (https://app.yiigle.com/cmaapp/). Results:From January 2019 to December 2021, 36 issues of Journal of Leukemia & Lymphoma were published, containing a total of 578 articles, with an average of about 16 articles per issue. There were 222 (38.4%) original articles, 173 (29.9%) brief communications, 11 (1.9%) guidelines and consensus articles, 58 (10.0%) topic reviews, and 94 (16.3%) reviews; the degree of authorship cooperation was 5.10 (2 946/578). The first author's affiliation included 28 provinces, cities and autonomous regions. The top 10 regions were Jiangsu, Henan, Beijing, Fujian, Shanxi, Guangdong, Tianjin, Shanghai, Hebei, and Shandong, with a total of 425 (73.5%) articles. There were 257 (44.5%) funded articles, including 105 (18.2%) articles funded by national funds. The average number of citations per article was 18.6 (10 751/578). The average annual number of reads was 104 630, and the top 20 most-read articles in 2021 were mostly in the category of guidelines and consensus and topical reviews. Conclusions:Journal of Leukemia & Lymphoma has developed well in recent years, and its influence in the field of hematology-oncology has steadily increased. In the future, according to the purpose of the journal, the special columns should be further created, and the academic quality should be improved to better serve the readers and authors.

OBJECTIVE To systematically evaluate the efficacy and safety of oral Janus kinase （JAK） inhibitor in the treatment of alopecia areata （AA）in order to provide evidence -based reference for clinical use . METHODS PubMed，Embase， Web of Science ，the Cochrane Library ，CNKI，Wanfang and CBM were searched from the inception to March 29，2022. Randomized controlled trials （RCTs）of oral JAK inhibitors （trial group ）versus placebo （control group ）in the treatment of AA were collected . Two researchers independently screened the literature ，extracted the data ，and evaluated the quality of the included studies. RevMan 5.4 software was used for meta -analysis and analysis of publication bias . RESULTS A total of 2 170 patients were enrolled in 5 RCTs，including 1 619 in the trial group and 551 in the control group . Meta-analysis results showed that ：compared with control group ，the ratio of the patients with the Severity Alopecia Tool （SALT）score ≤20 at 24th week [RR＝6.10，95%CI （3.86，9.63），P＜0.000 01] and 36th week [RR＝6.59，95%CI（4.16，10.43），P＜0.000 01] were both higher ；Hospital Anxiety and Depression Scale -Anxiety （HADS-A） score [RR＝0.35， 95%CI （0.07，0.64），P＝0.02] and Hospital Anxiety and 1009） Depression Scale -Depression （HADS-D） score [RR＝0.50， 95%CI（0.22，0.77），P＝0.000 4] were more decreased at 24th week . HADS-A score [RR＝0.55，95%CI（0.21，0.89）， 话：0371-66913047。 P＝0.001] and HADS -D score [RR＝0.50， 95%CI （0.16，0.84），P＝0.004] were also significantly decreased at 36th week . The incidence of acne [RR＝4.07，95%CI（1.83，9.08），P＝0.000 6] and low density lipoprotein （LDL）elevation [RR＝1.66，95%CI（1.21，2.28），P＝0.002] in trial group were incr eased significantly （P＜0.05）. There were no significant differences in the incidence of urinary tract infection，upper respiratory tract infection ， headache，nasopharyngitis and creatine phosphokinase elevation between 2 groups （P＞0.05）. There was little possibility of publication bias in this study based on the publication bias analysis . CONCLUSIONS Oral JAK inhibitor can significantly improve AA patients ’hair regrowth ，anxiety and depression . Acne and LDL elevation are the main adverse events .

OBJECTIVE: To explore the genetic basis for a child with metachromatic leukodystrophy (MLD). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Potential variant was screened by whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing. The pathogenicity the variant was analyzed by multiple sequence alignment of the amino acid sequence and three-dimensional model prediction of its protein product. RESULTS: The child was found to harbor compound heterozygous variants c.257G>A (p.R86Q) and c.467del (p.G156Afs*6) of the ARSA gene, among which the c.467del (p.G156Afs*6) frameshift variation was unreported previously. Multiple sequence alignment showed that the site of the c.257G>A (p.R86Q) missense variant is highly conserved. Three-dimensional structure modeling analysis showed that the partial deletion due to the p.G156Afs*6 variant may cause significant alteration of the structure of ARSA protein. CONCLUSION The discovery of novel variant in ARSA has enriched the mutational spectrum of MLD and may facilitate the understanding of the genotype-phenotype correlation of MLD.
Cerebroside-Sulfatase/genetics* ; DNA ; Genetic Association Studies ; Humans ; Leukodystrophy, Metachromatic/genetics* ; Mutation

Objective:To analyze the articles and literature indicators of Cancer Research and Clinic, in order to provide reference for the development of the journal. Methods:All articles published in Cancer Research and Clinic from January 2017 to December 2021 were searched on the official website of the journal (www.zlyjylc.com.cn), and the core literature indicators of Cancer Research and Clinic published in the Citation Report of Chinese Science and Technology Journals (Core Edition) from 2018 to 2022 were searched, and the statistical analysis of the articles and literature indicators was performed using bibliometric method and Excel software. Results:From 2017 to 2021, a total of 60 issues of Cancer Research and Clinic were published, containing a total of 1 065 articles, with an average of 17.8 articles per issue; a total of 4 416 pages of articles were published, with an average of 4.1 pages per article. There were 609 original articles (57.2%), 193 brief communications (18.1%) and 224 reviews (21.0%) in the main sections. The degree of authorship cooperation was 3.84 (4 086/1 065). The first author affiliation of the article was located in 31 regions, of which the top 10 regions in terms of the number of articles published were Shanxi, Jiangsu, Beijing, Shandong, Hubei, Shaanxi, Liaoning, Guangdong, Henan, and Hebei, with a total of 822 articles (77.2%). A total of 487 articles (45.7%) were funded by the foundation, including 134 articles (12.6%) funded by the national foundations. The average number of citations per article was 19.3 (20 557/1 065); the total number of marked keywords was 4 412, with an average of 4.1 per article. The impact factor and total citation frequency in 2018 were the highest (0.680 and 775), and the rate cited, open factor and overall evaluation total score in 2021 were the highest (0.94, 42 and 29.8). Conclusions:Cancer Research and Clinic has adhered to its own purpose and formed its own characteristics, and its academic quality and influence have steadily improved in the field of oncology in China in recent years. It should continue to improve the quality and strive to be a first-class oncology journal in the future.

Water is an important component in liquid medical device products for human assisted reproductive technology. Water traits, conductivity, microbial limits, total organic carbon, easy oxides, heavy metal content, bacterial endotoxin and other indicators have an important impact on sperm, egg and embryo development in vitro, so for such products, the quality of water control is extremely important. The production water for producing such products is generally prepared by MilliQ purification system. In this research, we used four different types of water to fabricate the IVF liquids. It included deionized reverse osmosis water, ultra purified water and ultra purified water without endotoxin or nucleic acid, and compared with tap water. The in vitro rat embryo test system was used to study the embryotoxicity of this four different culture liquid production waters. From the result, the group of the super purified water without endotoxin and nucleic acid has the best result of the embryo formation rate, the number of total cell number and the inner cell number. This study proved the importance of removing endotoxin and nucleic acid from the water used for the preparation of the liquid products for assisted reproduction, and provided the basis for the selection of water quality for the liquid products for assisted reproduction.
Animals ; Embryonic Development ; Equipment Contamination ; Fertilization in Vitro/instrumentation* ; Humans ; Rats ; Reproductive Techniques, Assisted ; Research ; Technology ; Water

Objective To study the safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection.Methods CNKI, Wanfang database , PubMed, Embase and Cochrane library were systematically searched.Randomized controlled trials about colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection were enrolled.The Cochrane Reviewers′Handbook 5.2 was employed to evaluate the quality of the enrolled studies. The primary outcome was all-cause mortality.The secondary outcomes included infection-related mortality, clinical response, bacterial clearance, nephrotoxicity and hepatotoxicity.Meta-analysis was conducted by RevMan 5.3 software.Results Seven articles containing 859 patients were finally included.There were no significantly statistical differences in all-cause mortality rate (relative risk [RR]＝1.07, 95%CI:0.93-1.24, P＞0.05), infection-related mortality rate (RR＝1.35, 95%CI:0.98-1.87, P＞0.05), bacterial clearance rate (RR＝0.85, 95%CI:0.71-1.02, P＝0.08), hepatotoxicity development rate (RR＝0.68, 95%CI:0.41-1.13, P＝0.14), and nephrotoxicity development rate (RR＝1.01, 95%CI:0.85-1.22, P＞0.05) between colistin monotherapy and combination therapy.The clinical response rate was higher in combination therapy than that in colistin monotherapy ( RR ＝0.81, 95%CI:0.66 -0.98, P ＝0.03).In the subgroup analysis, no statistical differences were found in all-cause mortality rate between colistin monotherapy and combination therapy for carbapenem-resistant Acinetobacter baumannii infection (RR＝1.00, 95%CI:0.86-1.12, P＞0.05). The dosage of colistin with or without loading dose was not associated with the treatment response .Conclusions Although colistin-based combination therapy has a better clinical response against carbapenem -resistant bacteria infection, especially for Acinetobacter baumannii infection, the mortality rate dose not decline compared to colistin monotherapy.Large-scale randomized controlled trials are needed to evaluate the effect in the future.

Objective To investigate the basic clinical features in 371 cases of colorectal polyps and its relationship with fecal occult blood and carcinoembryonic antigen(CEA).Methods The retrospective analysis was performed on 371 inpatients with colo-rectal polyps.The relationship among gender,number of polyps and polyps anatomical site in different ages of patients was investi-gated,and the relationship between fecal occult blood and CEA with polyp canceration was analyzed by 1.5?3.0 years follow-up. Results Among 371 cases of colorectal polyps,the female patients were gradually increased and single polyp was gradually de-creased along with the age increase;due to different ages,there was the statistically significant difference in the polyp locations (χ2 =9.759,P=0.045);the distribution difference of the patients with polyp canceration among three age groups was statistically significant(χ2 =5.138,4.107,13.153,P<0.05).The cases of fecal occult blood positive and CEA abnormal increase were gradual-ly increased with age increasing(χ2 =15.544,11.959,P<0.01);with the number of polyps increasing,the cases of fecal occult blood positive showed the increasing trend(χ2 =14.043,P=0.001);the canceration rate in colorectal polyp cases of fecal occult blood positive and CEA abnormal increase was significantly higher than that in the cases of fecal occult blood negative and CEA normal range(χ2 =40.165,43.249,all of P< 0.001).Conclusion The fecal occult blood test and CEA detection results have a certain significance to the follow up for preventing colorectal polyps canceration.