[Retrospective study of 70 cases with the head and neck non-parameningeal rhabdomyosarcoma].

Objective: To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS). Methods: A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children's Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test. Results: A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis (χ2=5.022, P=0.025), distant metastasis (χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group (χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion: Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

[Consideration on the possible etiological mechanisms and countermeasures about severe acute hepatitis of unknown origin in children].

Since April 2022, severe acute hepatitis of unknown origin in children has spread to 35 countries and regions around the world, and more than 1 010 cases have been reported. Since the severe acute hepatitis of unknown origin involves a wide range of areas and has a high rate, it is critical to identify the etiology and establish effective preventive, diagnostic and therapeutic measures as soon as possible. This study discusses the possible mechanisms and countermeasures of the severe acute hepatitis of unknown origin in children. It speculates that the occurrence of the recent severe acute hepatitis might be related to adenovirus, adeno-associated virus infection, and the COVID-19 epidemic, while the difference in HLA polymorphism among different races might be related to the fact that reported cases were more common in Europe and the United States. Based on the currently available evidence, it can be preliminarily judged that the risk of large-scale outbreak of severe acute hepatitis of unknown origin in children would be low in China, but the persistent awareness and vigilance of the etiology is still needed.

[Case-control study of female breast cancer and occupational risk factors based on lasso logistic regression in Beijing].

Objective: To understand the relationship between female breast cancer and occupational risk factors in Beijing, and provide scientific basis for the formulation of prevention strategies and measures. Methods: From June to December 2019, A 1: 1 case-control study was adopted, eight medical institutions in Beijing were selected as the research objects. Patients with breast cancer diagnosed by medical institutions were selected as case group and non breast cancer patients in the same medical institution as control group. A total of 973 subjects were included, including 495 in the case group and 478 in the control group. A one-to-one survey was conducted using a questionnaire uniformly compiled by the Beijing Centers for Disease Control and Prevention. The survey content mainly includes basic demographic characteristics and occupational risk factors. The Trait Coping Style Questionnaire (TCSQ) was used to investigate the corresponding methods, including two aspects: positive coping and negative coping. First, chi square test or Wilcoxon rank sum test were used for univariate analysis. Then Lasso regression was used to screen the risk factors of breast cancer. Finally, the risk factors were screened by multivariate logistic regression analysis. Results: Education lovel was 49.64%, body mass index (BMI) was 18.4~23.9 kg/m(2), accounting for 48.82%, marital status ws 84.48%. Compared with no night shift history, there was a significant increase in risk of breast cancer at night shift history (OR=1.70, 95% CI: 1.25~2.30, P<0.05) . Compared with most of the sitting posture and sometimes standing, the risk of breast cancer was increased, and the difference was statistically significant (OR=2.01, 95%CI: 1.40~2.90, P<0.05) . Conclusion: In the occupation risk factors, night shift work and working posture are related to the incidence of breast cancer in women, establishing a good schedule and avoiding long standing can effectively prevent and reduce the occurrence of breast cancer.

Tau Pathologies Mediate the Associations of Vascular Risk Burden with Cognitive Impairments in Non-demented Elders: The CABLE Study.

BACKGROUND: Studies suggested that vascular dysfunction might increase the risk of developing Alzheimer's disease (AD), but the underlying mechanisms still remain obscure. OBJECTIVE: To evaluate the associations of vascular risk burden with AD core pathologies and investigate the effects of AD core pathologies on relationships between vascular risk burden and cognitive impairments. DESIGN: The Chinese Alzheimer's Biomarker and LifestyLE (CABLE) study was principally focusing on aging, as well as the risk factors and biomarkers of AD initiated in 2017. SETTING: The CABLE study was a large cohort study established in Qingdao, China. PARTICIPANTS: A total of 618 non-demented elders were obtained from CABLE study. MEASUREMENTS: The general vascular risk burden was assessed by the Framingham General Cardiovascular Risk Score (FGCRS). Multivariate linear regression analyses were performed to evaluate the associations of FGCRS with cerebrospinal fluid (CSF) AD biomarkers and cognition. Casual mediation analyses were performed to investigate the mediating effects of AD biomarkers on cognition. RESULTS: Increased FGCRS was related to higher levels of CSF total tau (t-tau, p < 0.001), phosphorylated tau (p-tau, p < 0.001) as well as the ratio of t-tau and amyloid-ß 42 (t-tau/Aß42, p = 0.010), and lower Chinese-Modified Mini-Mental State Examination (CM-MMSE, p = 0.010) score. Stratified analysis indicated that age modified the associations, with FGCRS being significantly associated with tau pathology (p < 0.001 for t-tau and p-tau) in middle-aged group (<65 years old), instead of older group. The influences of FGCRS on cognitive impairments were partially mediated by tau pathologies (a maximum proportion of 20.9%). CONCLUSIONS: Tau pathology might be a pivotal mediator for effects of vascular risk on cognitive decline. Early and comprehensive intervention for vascular risk factors might be a potential approach to delaying or preventing cognitive impairment and AD.

[Efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma].

Objective: To evaluate the efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma (HNRMS). Methods: Information from 45 children diagnosed as non-orbital HNRMS and subjected to surgery combined with neoadjuvant chemoradiotherapy in Beijing Children's Hospital affiliated to Capital Medical University from August 2017 to July 2021 was analyzed. The patients included 25 males and 20 females, aged from 1 to 17 years old. The primary tumor site, pathological subtype, clinical stage, risk group, therapeutic regimen, resection range and outcome of all cases were also collected. The survival curves were made using the Kaplan-Meier method and the potential prognostic factors were investigated by Cox regression analysis. Results: Fifteen (33.3%) of 45 children achieved negative surgical margin under complete tumor resection. The postoperative pathological results showed that there were 20 cases of embryonic subtype, 19 cases of alveolar subtype and 6 cases of spindle sclerosis subtype. The postoperative follow-up time ranged from 4 to 71 months, with a median of 26 months. During the follow-up period, 13 children died, among whom brain metastasis was the most common cause of death, accounting for 7/13. The 3-year overall survival rate was 67.6%. Multivariate analysis showed that non-embryonic subtype (HR=6.26, 95%CI: 1.52-25.87, P=0.011) and failure to reach R0 resection (HR=9.37, 95%CI: 1.18-74.34, P=0.034) were independent risk factors affecting overall survival rate. Conclusion: Surgery combined with neoadjuvant chemoradiotherapy can offer a good efficacy for children with non-orbital HNRMS. Non-embryonic subtype and resection without negative operative microscopic margins are independent risk factors for poor prognosis, and brain metastasis is the main cause of death in these children.

[A retrospective study of hemophilic pseudotumor in maxillofacial region].

Objective: To provide clinical references for the diagnosis and treatment of hemophilic pseudotumor (HPT) in maxillofacial region. Methods: Fourteen cases of HPT in maxillofacial region from the Department of Stomatology, Beijing Children's Hospital from Jan 2009 to Jan 2019 were collected. Two cases were lost for follow-up and 12 patient,all boys, were finally followed up and included in the study. The patients aged from 13 months to 10 years old. The medical history, clinic manefestitions and the features of the radiology examination were recorded. The patients were treated by using replacement treatment first. If the conservative treatment was not effective, the patients then received operation combined with pereoperation replacement thearapy. The patients were followed up for 13 months to 10 years.There were 11 cases of hemophilia A, and 1 case of hemophilia B. Two cases were severe type, the others (10/12) were mild and moderate types. Only 1 case was diagnosed as hemophilia initially. Nine cases (9/12) were misdiagnosed as malignant tumors, 1 case was misdiagnosed as osteomyelitis and 1 case was misdiagnosed as hemangioma. Only 3 cases had identified history of trauma before. Results: All cases were treated with replacement therapy first, among which 10 cases were effective, 8 cases were cured by conservative therapy, 1 case had residual soft tissue fistula after conservative treatment and 1 case recurrented after conservative treatment for 8 months. Two patients with poor efficacy to the replacement treatment were performed operations and finally were cured. Conclusions: The misdiagnosis rate of HPT in maxillofacial region was high. The conservative factor replacement therapy could achieve good results in most children and could be used as the preferred treatment. If the conservative treatment was not effective, the surgical treatment was also a safe option.

[An analysis of the evaluation results of symptom checklist 90 for female medical workers].

Objective: To evaluate the mental health of female doctors and nurses. Methods: Investigat the psychologic status of female doctors and nurses using symptom checklist 90. And statistical software was applied to analyze results of symptom checklist 90. Results: There were differences in the score of SCL-90 between doctor and nurse groups, the difference was statistically significant (P<0.05) . Negative life events (OR=2.940) , relative suffer from mental illness (OR=3.683) , shift work (OR=1.611) and heavy workload (OR=2.265) were found to risk factors for the positive of SCL-90. Conclusion: There were differences in the score of SCL-90 between doctor and nurse groups. Negative life events, relative suffer from mental illness, shift workand heavy workload are risk factors for SCL-90 positive of female doctors and nurses.

[An investigation and analysis of abnormal menstruation in female nurses in a hospital in Beijing, China].

Objective: To investigate the status of abnormal menstruation in female nurses in a comprehensive hospital in Beijing, China and related influencing factors. Methods: In July 2016, a cross-sectional survey was performed, and a self-administered questionnaire was used to investigate the status of menstruation and occupation in female nurses in a comprehensive hospital in Beijing. The chi-square test and a multivariate logistic regression analysis were used for statistical analysis. Results: A total of 892 female nurses were investigated, and among them, 485 experienced abnormal menstruation within the past three months, resulting in an abnormal menstruation rate of 54.37%. The female nurses who were exposed to harmful factors during work, negative life events, or high workload had a significantly higher abnormal menstruation rate than those who were not exposed to such factors (χ(2)=5.199, 16.186, and 10.227, P<0.05 or P<0.01) . Negative life events (odds ratio [OR]=1.813, 95% confidence interval[CI]: 1.317-2.496) and high workload (OR=1.461, 95%CI: 1.112-1.918) were risk factors for abnormal menstruation. Conclusion: Nurses have an abnormal menstruation rate as high as 54.37%, and high workload and negative life events were risk factors for abnormal menstruation in nurses.

[Prevalence of reproductive system diseases among female workers in a city and related occupational influencing factors: an analysis of 9944 cases].

Objective: To investigate the prevalence of reproductive system diseases among female workers in a city and related occupational influencing factors. Methods: From June to September, 2016, a cross-sectional survey was used to select 9 944 female workers from six districts of Beijing and then a face-to-face questionnaire survey was performed. Univariate analysis using chi-square test and multivariate logistic regression analysis were used to investigate the risk factors for reproductive system diseases. Results: The age of 9944 female workers ranged from 18 to 65 years (mean 35.53±9.52 years) , and among them, 7 351 (73.92%) were married. The overall prevalence rate of reproductive system diseases among these 9944 female workers during the past three months was 28.29%, and the prevalence rates of hyperplasia of mammary glands, vaginitis, and hysteromyoma were 15.54%, 11.25%, and 6.77%, respectively. After adjustment for age, marital status, education level, and annual family income, the multivariate logistic regression analysis showed that frequent overtime work (odds ratio[OR]=1.119, 95% confidence interval[CI]: 1.070-1.343) , frequent night shifts (OR=1.198, 95%CI: 1.054-1.361) , standing for a long time (OR=1.197, 95%CI: 1.063-1.347) , sitting for a long time (OR=1.327, 95%CI: 1.191-1.479) , heavy workload (OR=1.429, 95%CI: 1.262-1.615) , exposure to lead (OR=1.696, 95%CI: 1.307-2.201) , exposure to mercury (OR=1.452, 95%CI: 1.086-1.940) , and exposure to ionizing radiation (OR=1.679, 95%CI: 1.424-1.980) were associated with reproductive system diseases. Conclusion: The prevalence of reproductive system diseases among female workers in Beijing is not optimistic. Reproductive system diseases are associated with frequent overtime work, frequent night shifts, standing for a long time, sitting for a long time, heavy workload, and exposure to lead, mercury, and ionizing radiation.

[An analysis of the evaluation results of symptom checklist 90 for occupational females in different industries].

Objective: To evaluate the mental health of occupational females in different industries. Methods: We investigated the psychologic status of Chinese occupational females using symptom checklist 90. And statistical software was applied to analyze results of symptom checklist 90. Results: There were 41, 166 effec-tive questionnaires. The number of positive questionnaires was 14 361, and the positive rate was 34.89%. The positive rate of obsessive-compulsive factor was 24.07%. The positive rate of somatization factor was 16.12%. The positive rate of depression was 15.50%. The median positive item number was 20 (IQR: 34) , and the median split of positive symptoms was 2.11 (IQR: 0.37) . There were differences in the positive rate of SCL-90 scale among different age groups, different regions and different industries, the difference was statistically significant (P<0.05) . The positive rate of SCL-90 for the occupational females was 34.89%. The top three factors of the high-est positive SCL-90 were obsessive-compulsive symptoms, somatization and depression. Conclusion: There were differences in the psychological status of occupational females for different regions, different ages and different occupations.

[Analysis of individualized primary prophylactic treatment of 19 cases of children with severe hemophilia A].

Objective: To study the current situation of primary prophylaxis in severe hemophilia A children and to explore rational regimen in order to provide evidence for the development of primary prophylaxis in China. Method: A retrospective clinical data collection and analysis was conducted for 19 severe hemophilia A children who received primary prophylaxis in Beijing Children's Hospital outpatient clinic between February 2011 and September 2015 and evaluated the regimen and efficacy. Result: (1) Primary prophylaxis regimen: the median beginning age 1.8 (range 0.5-2.9) years, the median FⅧ preparation using dosage 16.7 (8.0-23.5) U/(kg·time), the median using frequency was 1.0 (1.0-3.0) time/week. Eight cases among the patients received escalation of treatment intensity because of the poor bleeding control. (2) Efficacy: the median annual bleeding rate (ABR) was 1.9 (0-6.0) times/year, the median annual joint bleeding rate (AJBR) was 0 (0-3.3) times/year, without life threatening bleeding. All of them kept in 4th scale of Beijing Children Hospital daily activity level. The median annual factor consumption was 1 844 (840-5 040) U/kg. Conclusion: Low-dose primary prophylaxis regimen which were in low-dose /low frequencies and adjusted by bleeding frequency could decrease bleeding and joint bleeding frequency significantly, maintained the normal daily activity capacity and saved the factor consumption compared to standard regimen in severe hemophilia A children.

Pathogenic Bacillus anthracis in the progressive gene losses and gains in adaptive evolution.

BACKGROUND: Sequence mutations represent a driving force of adaptive evolution in bacterial pathogens. It is especially evident in reductive genome evolution where bacteria underwent lifestyles shifting from a free-living to a strictly intracellular or host-depending life. It resulted in loss-of-function mutations and/or the acquisition of virulence gene clusters. Bacillus anthracis shares a common soil bacterial ancestor with its closely related bacillus species but is the only obligate, causative agent of inhalation anthrax within the genus Bacillus. The anthrax-causing Bacillus anthracis experienced the similar lifestyle changes. We thus hypothesized that the bacterial pathogen would follow a compatible evolution path. RESULTS: In this study, a cluster-based evolution scheme was devised to analyze genes that are gained by or lost from B. anthracis. The study detected gene losses/gains at two separate evolutionary stages. The stage I is when B. anthracis and its sister species within the Bacillus cereus group diverged from other species in genus Bacillus. The stage II is when B. anthracis differentiated from its two closest relatives: B. cereus and B. thuringiensis. Many genes gained at these stages are homologues of known pathogenic factors such those for internalin, B. anthracis-specific toxins and large groups of surface proteins and lipoproteins. CONCLUSION: The analysis presented here allowed us to portray a progressive evolutionary process during the lifestyle shift of B. anthracis, thus providing new insights into how B. anthracis had evolved and bore a promise of finding drug and vaccine targets for this strategically important pathogen.

A versatile computational pipeline for bacterial genome annotation improvement and comparative analysis, with Brucella as a use case.

We present a bacterial genome computational analysis pipeline, called GenVar. The pipeline, based on the program GeneWise, is designed to analyze an annotated genome and automatically identify missed gene calls and sequence variants such as genes with disrupted reading frames (split genes) and those with insertions and deletions (indels). For a given genome to be analyzed, GenVar relies on a database containing closely related genomes (such as other species or strains) as well as a few additional reference genomes. GenVar also helps identify gene disruptions probably caused by sequencing errors. We exemplify GenVar's capabilities by presenting results from the analysis of four Brucella genomes. Brucella is an important human pathogen and zoonotic agent. The analysis revealed hundreds of missed gene calls, new split genes and indels, several of which are species specific and hence provide valuable clues to the understanding of the genome basis of Brucella pathogenicity and host specificity.

Knowledge-based voting algorithm for automated protein functional annotation.

Automated annotation of high-throughput genome sequences is one of the earliest steps toward a comprehensive understanding of the dynamic behavior of living organisms. However, the step is often error-prone because of its underlying algorithms, which rely mainly on a simple similarity analysis, and lack of guidance from biological rules. We present herein a knowledge-based protein annotation algorithm. Our objectives are to reduce errors and to improve annotation confidences. This algorithm consists of two major components: a knowledge system, called "RuleMiner," and a voting procedure. The knowledge system, which includes biological rules and functional profiles for each function, provides a platform for seamless integration of multiple sequence analysis tools and guidance for function annotation. The voting procedure, which relies on the knowledge system, is designed to make (possibly) unbiased judgments in functional assignments among complicated, sometimes conflicting, information. We have applied this algorithm to 10 prokaryotic bacterial genomes and observed a significant improvement in annotation confidences. We also discuss the current limitations of the algorithm and the potential for future improvement.

Genome-scale expression of proteins from Bacillus subtilis.

We have applied high throughput methods for cloning and expression of more than 850 genes from the Bacillus subtilis genome. The process uses 96-well plates and is automated from the level of primer design to the detection of soluble protein by a tag detection screen. This process was applied to a set of cytoplasmic targets from Bacillus subtilis to produce clones expressing soluble protein for incorporation into the structure determination pipeline of the Midwest Center for Structural Genomics. We also evaluated the feasibility of these plate-based methods for domain-based cloning and expression of secretory proteins and putative soluble domains of membrane proteins. This approach shows promise for implementation in a high throughput format and could provide additional target resources for structure determination. The continued development of new technologies that can be implemented in an automated format will be essential for continued success in the structural genomic programs.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Chinese family: clinical, radiological and skin biopsy features.

We describe the clinical, radiological, genetic and skin biopsy findings of the first Chinese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of the 43-member family tree extending over three generations, eight had typical clinical features of CADASIL with recurrent ischemic stroke. In the three surviving affected family members, brain MRI showed extensive leukoaraiosis. Genotyping revealed heterozygous C to T mutation at nucleotide 406 in exon 3. Unusual clinical features were cerebellar infarction as a presenting complaint and a late age of onset with mild symptoms at age 69. A novel finding is the suggestion of a direct correlation between clinical disease severity and the quantity of ultrastructural pathognomonic granular osmophilic material (GOM) seen on skin biopsy.

Sentra, a database of signal transduction proteins.

Sentra (http://www-wit.mcs.anl.gov/sentra) is a database of signal transduction proteins with the emphasis on microbial signal transduction. The database was updated to include classes of signal transduction systems modulated by either phosphorylation or methylation reactions such as PAS proteins and serine/threonine kinases, as well as the classical two-component histidine kinases and methyl-accepting chemotaxis proteins. Currently, Sentra contains signal transduction proteins from 43 completely sequenced prokaryotic genomes as well as sequences from SWISS-PROT and TrEMBL. Signal transduction proteins are annotated with information describing conserved domains, paralogous and orthologous sequences, and conserved chromosomal gene clusters. The newly developed user interface supports flexible search capabilities and extensive visualization of the data.

Thermal and photochemical epimerization/equilibration of carbohydrate cobaloximes.

Epimeric carbohydrate alkyl cobaloximes 4:5, 9:10, and 12:13 can be equilibrated thermally or photochemically. In each case, one isomer is strongly favored: exo-3-deoxy-3-pyridyldimethylglyoximatocobalt-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose 4 for the 4:5 epimer pair, exo-3-deoxy-3-pyridyldimethylglyoximatocobalt-5-O-carboxymethyl-1,2-O-isopropylidene-alpha-D-xylofuranose 9 for the 9:10 epimer pair, and equatorial 1-deoxy-1-pyridyldimethylglyoximatocobalt-2,3,4,6-tetra-O-benzyl-beta-D-glucopyranose 12 for the 12:13 epimer pair. These data indicate that there is a strong facial preference for the coupling of py(dmgH)(2)Co(*) radicals with alkyl R(*) free radicals, with the preferred kinetic path leading to the more stable product.

[Patient-controlled analgesia with lornoxicam in patients undergoing gynecological surgery].

OBJECTIVE: To assess the analgesic effect and side effects of PCA with lornoxicam compared with morphine and tramadol. METHODS: 89 patients, scheduled for elective hysterectomy or hysteromyomectomy, were randomly divided into Group L, Group M and Group T. Three drugs administered i.v. via a patient-controlled analgesia for up to 24 h postoperatively. RESULTS: Efficacy was assessed by comparing total pain relief (TOTPAR) and sum of pain intensity difference (SPID) over 24 h. Statistically significant equivalence of lornoxicam, morphine and tramadol was shown by TOTPAR values 15.2 +/- 3.9, 16.4 +/- 3.5 and 15.9 +/- 4.4, by SPID values 10.3 +/- 3.1, 9.0 +/- 2.0 and 9.2 +/- 4.7, respectively (P > 0.05). Lornoxicam caused fewer adverse events than morphine and tramadol (10.0%, 26.7% and 17.2% of patients, respectively). CONCLUSION: The study suggests that lornoxicam provides an alternative to morphine or tramadaol for the treatment of postoperative pain.