Objective To investigate the expressions of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-9(MMP-9),lysine demethylase 6B(KDM6B)proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.Methods The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People's Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens＞1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic(ROC)curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.Results The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues(P＜0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＞0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer(P＞0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer(P＞0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis(TNM)staging of invasive breast cancer(P＜0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P＜0.05).In the WHO grades Ⅰ,Ⅱ,and Ⅲ of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages Ⅲ-Ⅳ were significantly higher than those in stages Ⅰ-Ⅱ(P＜0.05),while the relative expression of KDM6B protein was significantly lower than that in stages Ⅰ-Ⅱ(P＜0.05).In the group of invasive breast cancer with diameter≤2 cm,2 to 5 cm,and＞5 cm,the relative expression of MMP-9 protein increased sequentially(P＜0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues(r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein(r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein(r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve(AUC)of EMMPRIN protein for diagnosing invasive breast cancer was 0.875[95％confidence interval(CI):0.823-0.926,P＜0.05],with an optimal threshold of 10.043,sensitivity of 79.0％,and specificity of 76.8％;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863(95％CI:0.808-0.917,P＜0.05),with an optimal threshold of 10.070,sensitivity of 74.2％,and specificity of 76.8％;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267(95％CI:0.196-0.338,P＜0.05),with an optimal threshold of 11.003,sensitivity of 71.0％,and specificity of 98.6％.Conclusion EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.

Objective: To explore the current status and progress of regional school health work to provide policy reference for school health improvement. Methods: Survey data on school health work in Tianjin from 2019, 2021 and 2023 was used. School health staff allocation and expenditure of the health administrative department, CDC and education department, as well as the annual implementation of health education, prevention and control of common diseases and infectious diseases, sports activities and food nutrition in primary and secondary schools were analyzed. Statistical analysis was conducted using KruskalWallis test, Chisquare test, and Fishers exact test. Results: The number of school health staff in the health commissions and education departments from 2019, 2021 and 2023 was relatively stable. Parttime staffs were often employed by health commissions while fulltime staffs were mainly employed by education departments. The number of school health staff at CDCs increased gradually (H=12.65, P<0.01). School health expenditure of administrative departments and schools in 2021 and 2023 increased significantly compared with that in 2019 (H=22.28, 23.75, P<0.05). More than 95% of schools set up clinics or health care rooms, and about 97% of schools had school health technicians or health teachers. More than 90% of schools had health education courses over 4 hours per semester. The rate of mental health education increased by year (86.87%, 89.91%, 96.30%, Z=2.40，P<0.05). Lack of courses regarded safety emergency and risk avoidance, growth and development, and adolescent health education. The provision rate of psychological counseling services (89.00%, 97.25%, 100.00%) and psychological problem prevention and control (56.12%, 71.56%, 81.48%) also increased by year (Z=3.83, 3.96, P<0.01). The implementation rates of prevention and control of poor vision, dental caries, overweight and obesity were all higher than 80%, and the prevention and control rate of abnormal spinal curvature showed an increasing trend (38.78%, 77.06%, 72.22%, Z=4.87, P<0.01). More than 90% of schools met the standard for physical education class hours, and the proportion of schools conducting at least 30 minutes of recess physical activities every day increased year by year (65.00%, 80.73%, 85.98%, Z=3.59, P<0.01). All schools did not have shops. Conclusions School health work in Tianjin is effective and constantly developing. It is necessary to continue to increase the investment of human resources and expenditure in school health, explore the approaches of cooccurrence and prevention of common diseases, and improve the school sports and nutrition environment.

Objective To explore the hot topics and the research trend of traditional Chinese medicine treatment of chronic obstruc-tive pulmonary disease in 2017-2021,and to aware the cooperation among authors and institutions in the field.Methods Literature on TCM treatment of chronic obstructive pulmonary disease published in CNKI and PubMed in 2017-2021 was searched,and CiteSpace 5.8 R3 was used to visualize the authors,research institutions and keywords of the included literatures.Results A total of 3082 Chinese literatures and 1093 English literatures were included.In 2017-2021,the trend of publication has always shown a steady growth,and there was a lack of communication and cooperation among authors and teams.Keywords visualization map showed 18 clusters and 20 emer-gent words.Conclusion Traditional Chinese medicine treatment of chronic obstructive pulmonary disease is mainly focused on syndrome type,treatment methods,disease mechanism and related curative effect indicators,and the syndrome differentiation analysis and clinical curative effect evaluation of traditional Chinese medicine compounds are still the main forces at present.As the patients quality of life is becoming more and more attention,how to strengthen pulmonary rehabilitation education,improve patient compliance,and expand the lo-cation and area of pulmonary rehabilitation is one of the current research trends.

Objective: To analyze the prevalence of comorbidity of spinal curvature abnormality and malnutrition among primary and secondary school students aged 10-18 years in Tianjin in 2023, so as to provide scientific basis for the combined prevention of common diseases and multiple diseases among students and the construction of school health system. Methods: In September to October 2023, 31 884 primary and secondary school students aged 10 to 18 years in Tianjin were selected using stratified cluster random sampling. Abnormal spinal curvature in children and adolescents was assessed by Sereening of Spinal Curvature Abnormality of Children and Adolescents, while stunting, wasting, overweight, and obesity were determined according to the Screening for Malnutrition among Schoolage Children and Adolescents and Screening for Overweight and Obesity among Schoolage Children and Adolescents. The χ2 test was used to compare betweengroup differences in coprevalence, and multiple Logistic regression models were used to analyze the risk of different comorbidity types in different clusters. Results: The coprevalence of spinal curvature abnormality and malnutrition among primary and secondary school students in Tianjin was 1.6%, which was higher for girls than boys (1.8%, 1.4%), higher (2.5%) for senior high schools than for junior high schools and elementary schools (2.0%, 0.5%), and higher in rural than in urban areas (2.1%, 1.1%) (χ2=9.45, 141.92, 46.94, P<0.05). Multiple Logistic regression models showed that junior high school girls had a higher risk of incorrect posture comorbid with stunting and wasting (OR=4.52, 95%CI=1.84-11.06) and incorrect posture comorbid with overweight and obesity (OR=2.67, 95%CI=1.74-4.10) than boys, and that scoliosis/sagittal spinal abnormality comorbid with stunting and wasting (OR=0.10, 95%CI=0.02-0.44) risk was lower than that of boys, senior high school girls had a lower risk of scoliosis/sagittal spinal abnormality comorbid with overweight and obesity (OR=0.27, 95%CI=0.11-0.66) (P<0.05). Conclusions The coprevalence of spinal curvature abnormality and malnutrition is specific among primary and secondary school students in Tianjin, and the comorbidity type varies by gender and education stage. There is a need to increase prevention and control of spinal curvature abnormalities in school health working, intensive screening of key populations, and timely intervention.

Objective:To investigate the clinicopathological features, molecular genetic features, and differential diagnosis of intraductal carcinomas (IDC) of the salivary glands.Methods:Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology, Shanghai Ninth People′s Hospital and two cases from Department of Pathology, Henan Provincial People′s Hospital, Zhengzhou, China from January 2008 to July 2023 were collected. Their clinical and pathological features were analyzed retrospectively. Fluorescence in situ hybridization and Sanger sequencing were performed. The patients were followed up and related literatures were reviewed.Results:There were 27 patients with IDC, including 15 males and 12 females, ranging in age from 20.0 to 80.0 years (mean 55.9 years). Clinically, the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm (mean 2.0 cm). All patients received surgical treatment. Twenty patients were followed up. One of them (1/20) died of lung cancer, while the rest survived without tumor recurrence. Histologically, IDC were classified as: intercalated (63.0%, 17/27), apocrine (25.9%, 7/27), oncocytic (7.4%, 2/27) and mixed (3.7%, 1/27) types. Intercalated tumors showed positive S-100 and negative androgen receptor (AR) immunoreactivity. Ki-67 proliferation index was low (about 1%-5%). Nine cases had the RET gene disruption, and 2 cases showed the BRAF V600E mutation. Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity. Ki-67 proliferation index was high (about 10%-60%), and the RET gene rupture was detected in 1 case. Oncocytic tumors were similar to that of intercalated type in 2 cases, and RET gene disruption was detected in the both cases. Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption.Conclusions:IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology. Molecular testing is helpful for its differential diagnosis.

Objective:To search, evaluate and summarize the best evidence of intervention and management of eating behavior in children with autism, so as to provide evidence for medical staff and caregivers of children with autism to manage eating behavior problems.Methods:According to the evidence pyramid "6S" model, the clinical decisions, recommended practices, guidelines, evidence summaries, expert consensus, systematic reviews and randomized controlled trials on the intervention and management of eating behavior in children with ASD were systematically searched from domestic and foreign databases, related guide websites and professional association websites. The search period was from the establishment of the database to March 31th, 2023. The quality of the guide was independently evaluated by 4 researchers, and the remaining articles were evaluated by 2 researchers. Content extraction, evidence integration and grading of the included articles were carried out, and the level of evidence recommendation was formed through the expert meeting.Results:A total of 19 articles were included, including 3 guidelines, 1 expert consensus, 13 systematic reviews and 2 randomized controlled trials. This paper summarized 25 best evidence from 5 aspects, including the common eating behavior problems of children with autism, the assessment of eating behavior problems, causes, consequences and intervention methods.Conclusions:The best evidence summarized in this study provides a basis for the management of eating behavior problems in children with autism. It is suggested that clinical staff should fully consider the clinical context when applying the evidence, and formulate more detailed and feasible eating behavior intervention programs combined with the children and their families.

Objective:To understand the regional prevalence and hotspot mutations through analysis of genetic screening results for newborns with pseudohypertrophic muscular dystrophy.Methods:A total of 22 813 newborns (12 065 males and 10 748 females) born at the Women's Hospital of Nanjing Medical University from March 18, 2022, to October 31, 2023, were selected. The Dystrophin gene ( DMD) was detected using chip capture next-generation sequencing technology, followed by bioinformatics analysis. Pathogenic mutations identified were validated using multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Serum creatine kinase levels were also tested in suspected male patients. Descriptive analysis was applied for this study. Results:Among the 10 748 girls, 14 carriers of DMD gene were detected (0.013%), of which, nine cases were validated in the family; one case was a de novo mutation, five were inherited from the mother, and three were inherited from the father. The screening identified nine suspected patients among the boys (0.075%), and eight of them were confirmed by family validation, in which three were de novo mutations, and five were inherited from the mother. Among all identified DMD mutations, deletions were the most common one, accounting for 52.2% (12/23), incluling four cases of deletion at 49-51 exon. Conclusions:Newborn genetic screening based on chip capture next-generation sequencing technology combined with bioinformatics analysis is helpful in early detection of patients and carriers of pseudohypertrophy muscular dystrophy. According to the preliminary statistics, the incidence rate of DMD/BMD in this area is 1/1 341 male infants and the hotspot mutation is exon 49 to 51 deletion.

Objective:To establish the cut-off value of tetradecenoyl carnitine (C14∶1)/dodecenoyl carnitine(C12∶1) based on non-derivatized tandem mass spectrometry (MS/MS), and to explore the application value of C14∶1/C12∶1 to screen newborns for very long chain acyl-CoA dehydrogenase deficiency (VLCADD), determining the best combination of indicators for screening VLCADD.Methods:This retrospective study included data from 17 newborns with VLCADD detected by MS/MS and confirmed by acyl-CoA dehydrogenase very long chain ( ACADVL) gene detection, and 423 507 newborns with normal MS/MS results. The data from these newborns were collected from January 2014 to December 2021 as the newborns received neonatal screening in Nanjing Neonatal Disease Screening Center and Suzhou Neonatal Disease Screening Center. All newborns were divided into 3 groups: all newborns group, full-term newborns group and normal-birth-weight newborns group, and the cut-off values of C14∶1/C12∶1 for VLCADD in these 3 groups were determined by their receiver operating characteristic (ROC) curves individually. With these results, a total of 5 interpretation schemes were composed using different indicators alone or jointly: scheme 1 being C14∶1/C12∶1, scheme 2 being C14∶1, scheme 3 being C14∶1+C14∶1/C2+C14∶1/C16, scheme 4 being C14∶1/C12∶1+C14∶1, and scheme 5 being C14∶1/C12∶1+C14∶1+C14∶1/C2+C14∶1/C16. The detection rate, false-positive rate and positive predictive value of each scheme were calculated, and their screening efficiencies were statistically compared by Chi-square tests. Results:The cut-off values of C14∶1/C12∶1 for VLCADD in the 3 newborn groups were all 2.80. The detection rates of VLCADD with all 5 interpretation schemes were 17/17. Scheme 1 had the highest false positive rate [26.15‰ (11 075/423 524)] and the lowest positive predictive value [0.15% (17/11 092)]. Scheme 4 (Scheme 5) had the lowest false positive rate [0.02‰ (10/423 524)] and the highest positive predictive value [62.96% (17/27)]. Comparing scheme 4 (Scheme 5) with scheme 1, scheme 2 and scheme 3, the differences of false positive rate (χ2=302.30,11 191.50,32.06) and positive predictive value (χ2=102.51,3 485.61,13.83) were statistically significant (all P<0.001). Conclusion:C14∶1/C12∶1 was an effective auxiliary interpretive indicator for VLCADD in newborn screening, and the combination of C14∶1/C12∶1+C14∶1 was tested to be the best indicator for VLCADD screening based on non-derivatized tandem mass spectrometry.

Objective:To analyze the results of ATP7B gene screening in neonates and explore the linkage disequilibrium between different mutation loci, providing a basis for the clinical diagnosis and genetic counseling of Wilson′s disease.Methods:A total of 12 619 newborns who were born in Women′s Hospital of Nanjing Medical University during March 18 and December 30, 2022, including 6 605 male neonates and 6 014 female neonates, with birth weight of (3.44±0.56) kg, were retrospectively collected. The results of ATP7B gene screening in all newborns were analyzed.Next-generation sequencing technology was employed to detect the pathogenic loci of ATP7B gene, and the identified loci were verified using Sanger sequencing. PLINK 1.9 software was used to analyze the linkage disequilibrium of different mutation loci.Results:Among 12 619 neonates, 22 cases were diagnosed with 2-3 pathogenic mutations in the ATP7B gene (suspected positive). Among them, 20 cases were recalled for family verification, and 2 cases refused to recall. The verification results showed that 3 newborns had mutations of two loci respectively from their parents and were preliminarily diagnosed with Wilson′s disease, the other 17 neonates were carriers of the c.3316G>A/c.588C>A or c.1708-1G>C/c.1168A>G mutation loci arranged in a cis-acting manner from the father source or maternal source. A total of 249 pathogenic mutation carriers were detected (232 cases carrying 1 pathogenic mutation, and 17 cases carrying 2 pathogenic mutations), with a carrier rate of 1/51. Among them, the mutation c.2333G>T was most frequently detected (1/207), followed by c.2975C>T (1/421), c.2621C>T (1/742), c.2755C>G (1/971) and c.2605G>A (1/971). The results of linkage disequilibrium analysis in both c.3316G>A/c.588C>A and c.1708-1G>C/c.1168A>G showed that D ′=1, which showed complete linkage disequilibrium. Conclusion:The carrier rate of pathogenic mutations in the ATP7B gene is relatively high.Moreover, the c.3316G>A/c.588C>A and c.1708-1G>C/c.1168A>G pathogenic mutation loci are likely to be arranged in a cis-acting manner, highlighting the existence of linkage disequilibrium between the two groups of mutations. This finding provides important reference value for the clinical diagnosis and genetic counseling of Wilson disease.

The facultative anaerobic and strict anaerobic microorganisms enriched and acclimated during the anaerobic digestion process are crucial for the efficiency of the anaerobic digestion system. Most of the problems encountered during running anaerobic digestion processes could be effectively improved via stimulation of microbial metabolic activity. Benefited from the rapid development of microbiome techniques, deeper insights into the microbial diversity in anaerobic digestion systems, e.g. the microbe-microbe interactions and microbe-environment interactions, have been gained. A complex and intricate metabolic network exists in the anaerobic digestion system of solid organic wastes. However, little is known about these interactions and the underlying mechanisms. This review briefly summarized the representative interactions between microbial communities during anaerobic digestion process discovered to date. In addition, typical issues encountered during the anaerobic digestion of solid organic wastes and how microbes can tackle and alleviate these issues were discussed. Finally, future priorities on microbiome research were proposed based on present contribution of microbiome analysis in anaerobic digestion system.
Anaerobiosis ; Bioreactors ; Methane ; Microbial Interactions ; Microbiota ; Solid Waste