[Development and application syndromic surveillance and early warning system in border area in Yunnan Province].

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.

[Clinicopathological features of mature T/NK cell lymphoma with aberrant CD20 or CD79α expression].

Objective: To investigate the clinicopathological characteristics and prognosis of mature T/NK cell lymphomas with aberrant CD20 or CD79α expression. Methods: A retrospective analysis of 641 cases of mature T/NK cell lymphoma diagnosed from January 2014 to December 2020 was performed, and 14 cases of CD20-positive and one case of CD79α-positive mature T/NK-cell lymphoma were identified. Histological examination, immunohistochemical characterization, in situ hybridization for Epstein-Barr virus encoded early RNA (EBER), and PCR testing for immunoglobulin and T cell receptor (TCR) gene rearrangements were performed. Clinicopathological characteristics of these lymphomas were analyzed. Results: There were 13 males and 2 females, with a median age of 56 years. There were 8 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 3 cases of extranodal NK/T-cell lymphoma, nasal type (ENKTCL), 2 cases of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and 2 cases of angioimmunoblastic T-cell lymphoma (AITL). Twelve cases were stage Ⅲ or Ⅳ lymphomas. The prognosis was overall poor. The histology, immunophenotype and TCR gene rearrangement were not significantly different from the corresponding types of lymphoma. Ki-67 proliferation index was over 70% in all cases. The expression of CD20 or CD79α was weak and heterogeneous. All 15 case of Ig gene rearrangement were polyclonal. Conclusions: Mature T/NK cell lymphoma with abnormal expression of CD20 or CD79α is rare, commonly found in advanced stage, and associated with poor prognosis. The expression of CD20 or CD79α in these cases is weaker than the corresponding mature T/NK cell lymphomas, while its proliferation index is higher. Histomorphology, extensive immunoprofiling and molecular detection are required for accurate diagnosis.

[Prenatal pyrethroid pesticides exposure and neurodevelopment of 2-year-old children: a birth cohort study].

Objective: To investigate the influence and critical windows of prenatal exposure to pyrethroid pesticides (PYRs) on neurodevelopment of 2-year-old children. Methods: The subjects of this study were derived from the Xuanwei Birth Cohort. A total of 482 pregnant women who participated in the rural district of Xuanwei birth cohort from January 2016 to December 2018 were included. Maternal urinary concentrations of PYRs metabolites during 8-12 gestational weeks, 20-23 gestational weeks and 32-35 gestational weeks were measured with ultra high performance liquid chromatography system coupled with a tandem mass spectrometry detector. Child neurodevelopment was evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition at 2 years of age. Multivariate linear regression models and binary logistic regression models were used to assess the association between PYRs exposure during pregnancy and children's neurodevelopment. Results: A total of 360 mother-child pairs had complete data on maternal urinary PYRs metabolites detection and children's neurodevelopment assessment. The detection rate of any one PYRs metabolites during the first, second and third trimester were 93.6% (337/360), 90.8% (327/360) and 94.2% (339/360), respectively. The neurodevelopmental scores of Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior of 2-year-old children were (102.3±18.9), (100.2±16.3), (102.0±20.3), (107.8±23.3) and (85.8±18.6) points, respectively. After controlling for confounding factors, 4-fluoro-3-phenoxybenzoic acid (4F3PBA, one of PYRs metabolites) exposure in the first trimester reduced Motor (ß=-5.02, 95%CI: -9.08, -0.97) and Adaptive Behavior (ß=-4.12, 95%CI:-7.92, -0.32) scores of 2-year-old children, and increased risk of developmental delay of adaptive behavior (OR=2.07, 95%CI:1.13-3.82). Conclusion: PYRs exposure during the first trimester of pregnancy may affect neurodevelopment of 2-year-old children, and the first trimester may be the critical window.

[Investigation for pathological interpretation criteria and its prognostic value for P53 expression in Chinese diffuse large B-cell lymphoma].

Objective: To explore the feasibility of predicting TP53 mutation risk by immunohistochemical staining (IHC) pattern of P53 in Chinese diffuse large B-cell lymphoma (DLBCL) and its correlation with a prognostic difference. Methods: Between January 2021 and December 2021, 51 DLBCL cases at Beijing Boren Hospital were gathered. These cases had both IHC and next-generation sequencing (NGS) results. IHC classified the P53 protein expression pattern into a loss (<1% ) , diffuse (>80% ) , and heterogeneous (1% -80% ) . The sensitivity and specificity of the predicting TP53 mutation by IHC were assessed by comparing the results of the NGS, and the TP53 high mutation risk group included both loss and diffuse expression of P53. From June 2016 to September 2019, Peking University Cancer Hospital collected 131 DLBCL cases with thorough clinicopathological and follow-up data. From their tumor blocks, tissue microarray blocks were made for IHC evaluation of P53 expression pattern, and prognosis effect of P53 studies. Results: Among 51 cases with both IHC and NGS results, 23 cases were classified as TP53 high mutation risk (7 cases loss and 16 cases diffuse) , 22/23 cases were proved with mutated TP53 by NGS. Only 1 of the 28 cases classified as TP53 low mutation risk was proved with mutated TP53 by NGS. IHC had a sensitivity and specificity of 95.7% and 96.4% for predicting TP53 mutation. NGS identified a total of 26 TP53 mutations with a mutation frequency of 61.57% (13.41% -86.25% ) . In the diffuse group, 16 missense mutations and 2 splice mutations were detected; 6 truncating mutations and 1 splice mutation were detected in the loss group; 1 truncating mutation was detected in the heterogeneous group. Multivariate analysis demonstrated that TP53 cases with high mutation risk have impartial adverse significance for the 131 patients included in survival analysis (HR=2.612, 95% CI 1.145-5.956, P=0.022) . Conclusion: IHC of P53 exhibiting loss (<1% ) or diffuse (>80% ) pattern indicated TP53 high mutation risk, IHC can predict TP53 mutation with high specificity and sensitivity. TP53 high mutation risk is an independent predictor for adverse survival.

Applying the zero-inflated Poisson model with random effects to detect abnormal rises in school absenteeism indicating infectious diseases outbreak.

Records of absenteeism from primary schools are valuable data for infectious diseases surveillance. However, the analysis of the absenteeism is complicated by the data features of clustering at zero, non-independence and overdispersion. This study aimed to generate an appropriate model to handle the absenteeism data collected in a European Commission granted project for infectious disease surveillance in rural China and to evaluate the validity and timeliness of the resulting model for early warnings of infectious disease outbreak. Four steps were taken: (1) building a 'well-fitting' model by the zero-inflated Poisson model with random effects (ZIP-RE) using the absenteeism data from the first implementation year; (2) applying the resulting model to predict the 'expected' number of absenteeism events in the second implementation year; (3) computing the differences between the observations and the expected values (O-E values) to generate an alternative series of data; (4) evaluating the early warning validity and timeliness of the observational data and model-based O-E values via the EARS-3C algorithms with regard to the detection of real cluster events. The results indicate that ZIP-RE and its corresponding O-E values could improve the detection of aberrations, reduce the false-positive signals and are applicable to the zero-inflated data.

[A prospective cohort study on the relationship between maternal prenatal depressive symptoms and children's behavioral problems at 2 years old].

Objective: To explore the associations between maternal and prenatal depressive symptoms and children's behavioral problems at 2 years old. Methods: In the present study, a total of 491 mother-child pairs were selected from the Shanghai-Minhang Birth Cohort Study (S-MBCS) which was conducted in Maternal and Child Health Hospital of Minhang District in Shanghai between April and December, 2012. Data from the Center for Epidemiologic Studies on Depression was gathered to assess the maternal depressive symptoms in the second and third trimester of pregnancy, as well as at 6 months and 12 months postpartum. Neurodevelopment at 2 years was assessed, using the Child Behavior Checklist. We used generalized linear models with a log-link function and a Binomial distribution to estimate the risk ratios (RRs) and 95%CIs, on children's behavioral problems at 2 years of age. Sensitivity analyses were performed among participants without postpartum depressive symptoms. Results: After adjustment on factors as maternal age, gestation week, average monthly income per person, parental education and children's gender etc., maternal depression in second trimester of pregnancy was found associated with higher risk of both developing emotional (RR=2.61, 95%CI: 1.36-4.99) and internalizing problems (RR=1.94, 95%CI: 1.22-3.08). However, maternal depression in third trimester was found to be associated with higher risks of developing emotional (RR=6.46, 95%CI: 3.09-13.53), withdrawn (RR=2.42, 95%CI: 1.16-5.02), aggressive (RR=2.93, 95%CI: 1.45-5.94), internalizing (RR=1.79, 95%CI: 1.01-3.16) or externalizing problems (RR=2.56, 95%CI:1.49-4.42). In sensitivity analysis, antenatal maternal depression was found positively associated with children's emotional, internalizing and externalizing problems and the differences all statistically significant. Conclusions: Maternal depression during pregnancy might increase the risks of children's behavioral problems. In order to decrease the incidence of children's behavioral problems and promoting both maternal and child health status, monitoring program regarding maternal mental health care should be strengthened.

The pathogenic detection for 126 children with diarrhea and drug sensitivity tests.

OBJECTIVE: To investigate the cause of infective diarrhea in children, special distribution of the infection and the drug sensitivity. PATIENTS AND METHODS: We carried out pathogenic detection and drug sensitivity tests for one hundred and twenty-six children with diarrhea, including 67 children in infant group (0-<1 year) and 59 children in child group (1-5 years). RESULTS: Fat particles and starch particles were seen in most stool samples under microscope; 42 kinds of pathogenic bacteria were obtained from 126 stool samples, including 10 Diarrheagenic E. coli (8 Enteropathogenic E. coli and Enteroinvasive E. coli); there were found 53 positive samples in the detection of anti-rotavirus antibody in 126 stool samples; in the drug sensitivity tests for major pathogenic bacteria, Staphylococcus aureus, Shigella, Salmonella and Diarrheagenic E. coli were highly sensitive. CONCLUSIONS: The abuse of antimicrobial agents may result in intestinal disorders, leading to aggravation in diarrhea and antimicrobial agents based on drug sensitivity tests may be served as fundamental treatment of diarrhea for children.

[A survey of HIV, HBV and HCV infections in children aged 1-13 years in Yi ethnic area, Sichuan province].

Objective: To investigate the prevalence of HIV, HBV and HCV infections in children aged 1-13 years in Yi ethnic area in Sichuan province. Methods: A cross-sectional study was conducted in the form of field survey in four townships selected from Yi ethnic area of Sichuan during 2014-2015. Participants were children aged 1-13 years by sample size of 900 and were screened for HIV antibody, HBV surface antigen and HCV antibody, and laboratory comfirmation was conducted. The area, age, gender and ethnic group specific infection rates were compared by using Fisher's exact test, and multiple comparisons were corrected by using Bonferroni correction. Results: A total of 677 children aged 1-13 years were surveyed. The infection rates of HIV, HBV and HCV were 1.03% (7/677, 95%CI: 0.42%-1.12%), 6.65% (45/677, 95%CI: 4.89%-8.79%) and 0.15% (1/677, 95%CI: 0%-0.82%), respectively. The infection rates of HIV differed among townships (P=0.000), the infection rate was higher in township D than in township B, the difference was significant (P<0.001). The differences in HIV infection rate among different age, gender and ethnic groups were not significant. The differences in HBV and HCV infections were not significant among different townships, age, gender and ethnic groups. The difference in HBV viral load between age group 5-9 years and age groups 10-13 years was not significant (U=115.000, P=0.967). Conclusions: The burden of HIV and HBV infections in children aged 1-13 years was heavy in rural area of Yi ethnic area in Sichuan. Therefore, it is necessary to take effective measures to block the vertical transmission of HIV and HBV as well as to increase the coverage of HBV vaccination.

Integrated Control Strategy of Schistosomiasis in The People's Republic of China: Projects Involving Agriculture, Water Conservancy, Forestry, Sanitation and Environmental Modification.

Among the three major schistosome species infecting human beings, Schistosoma japonicum is the only endemic species in The People's Republic of China. Schistosomiasis is endemic in 78 countries and regions and poses a severe threat to public health and socioeconomic development. Through more than 60years of hard work and endeavour, The People's Republic of China has made considerable achievements and reduced the morbidity and prevalence of this disease to the lowest level ever recorded, especially since the introduction of the new integrated control strategy in 2004. This review illustrates the strategies implemented by giving successful examples of schistosomiasis control from the different types of remaining endemic areas. The challenge to control or eliminate S. japonicum is analysed in order to provide useful information to policy makers and scientists.

Geographical variations of risk factors associated with HCV infection in drug users in southwestern China.

Hepatitis C virus (HCV) has become a global public health problem. Many studies have been conducted to identify risk factors for HCV infection. However, some of these studies reported inconsistent results. Using data collected from 11 methadone clinics, we fit both a non-spatial logistical regression and a geographically weighted logistic regression to analyse the association between HCV infection and some factors at the individual level. This study enrolled 5401 patients with 30·0% HCV infection prevalence. The non-spatial logistical regression found that injection history, drug rehabilitation history and senior high-school education or above were related to HCV infection; and being married was negatively associated with HCV infection. Using the spatial model, we found that Yi ethnicity was negatively related to HCV infection in 62·0% of townships, and being married was negatively associated with HCV infection in 81·0% of townships. Senior high-school education or above was positively associated with HCV infection in 55·2% of townships of the Yi Autonomous Prefecture. The spatial model offers better understanding of the geographical variations of the risk factors associated with HCV infection. The geographical variations may be useful for customizing intervention strategies for local regions for more efficient allocation of limited resources to control transmission of HCV.

Gene expression profiling of Duchenne muscular dystrophy reveals characteristics along disease progression.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy with no cure currently available. In this study, using two microarray data sets obtained from the Gene Expression Omnibus database, we conducted a dysfunctional pathway-enrichment analysis and investigated deregulated genes that are specific to different phases of the disease in order to determine pathogenic characteristics in the progression of DMD. We identified 41 and 33 dysfunctional pathways that were enriched with differentially expressed genes in presymptomatic patients and in symptomatic patients, respectively. Over 70% of pathways were shared between both phases and many of them involved the inflammatory process, suggesting that inflammatory cascades were induced soon after the birth of the patients. Further investigation showed that presymptomatic patients performed better with respect to muscle regeneration and cardiac muscle calcium homeostasis maintenance. Neuronal nitric oxide synthase, dihydropyridine receptors, sarcoplasmic/endoplasmic reticulum calcium ATPase, and phospholamban may serve as potential targets for further molecular diagnostic tests. Our results may provide a better understanding for the treatment of DMD.

Analysis of differentially expressed genes in various stages of Duchenne muscular dystrophy by using a network view.

Duchenne muscular dystrophy (DMD), which is caused by mutations in the X-linked dystrophin gene, is a severe and progressive neuromuscular disease with no available cure. By integrating 2 microarray datasets from the Gene Expression Omnibus, we identified differentially expressed genes in 2 stages of DMD and systematically explored their potential disease-related mechanisms using a network view. Twenty differentially expressed genes were detected in various stages of DMD. According to the network with dystrophin as its center, none of the 20 proteins interacts with dystrophin directly. IQ motif-containing GTPase-activating protein 1 was found in the 2nd-level neighbors with a degree of 21. Microtubule-associated protein tau, membrane metallo-endopeptidase, interleukin 13 receptor alpha 1, and multiple epidermal growth factor-like domains 6 were found in the 3rd-level neighbors. These identifications require further investigation, as this report is the first of possible associations between DMD and these proteins. Analysis of differentially expressed genes through this network view may provide important information for further exploration of underlying mechanisms of DMD.

Heritable alteration in DNA methylation induced by nitrogen-deficiency stress accompanies enhanced tolerance by progenies to the stress in rice (Oryza sativa L.).

Cytosine methylation is responsive to various biotic- and abiotic-stresses, which may produce heritable epialleles. Nitrogen (N)-deficiency is an abiotic stress being repeatedly experienced by plants. To address possible epigenetic consequences of N-deficiency-stress, we investigated the stability of cytosine methylation in rice (Oryza sativa L.) subsequent to a chronic (a whole-generation) N-deficiency at two levels, moderate (20mg/L) and severe (10mg/L), under hydroponic culture. MSAP analysis revealed that locus-specific methylation alteration occurred in leaf-tissue of the stressed plants (S(0)) experiencing either level of N-deficiency, which was validated by gel-blotting. Analysis on three non-stressed self-fed progenies (S(1), S(2) and S(3)) by gel-blotting indicated that ca. 50% of the altered methylation patterns in somatic cells (leaf) of the stressed S(0) plants were recaptured in S(1), which were then stably inherited to S(2) and S(3). Bisulfite sequencing of two variant MSAP loci with homology to low-copy retrotransposons on one stressed plant (S(0)) and its non-stressed progenies (S(1) and S(2)) showed that whereas one locus exhibited limited and non-heritable CHH methylation alteration, the other locus manifested dramatic heritable hypermethylation at nearly all cytosine sites within the assayed region. Intriguingly, when two groups of S(2) plants descended from the same N-deficiency-stressed S(0) plant were re-subjected to the stress, the group inheriting the modified methylation patterns showed enhanced tolerance to the N-deficiency-stress compared with the group bearing the original patterns. Our results thus demonstrate heritability of an acquired adaptive trait in rice, which was accompanied by epigenetic inheritance of modified cytosine methylation patterns, implicating an epigenetic basis underlying the inheritance of an acquired trait in plants.

Effect of chondroitin sulfate C on sperm capacitation and fertilization parameters in vitro in pigs.

The objective of this study was to determine the effects of chondroitin sulfate C (CS-C) on sperm capacitation and fertilization parameters in vitro in pigs. Frozen-thawed ejaculated pig sperm (semen S-484) were incubated with fertilization medium containing CS-C (0-2mg/ml) for 1h and the capacitation rate with chlorotetracycline (CTC) assay was examined, which showed that CS-C increased the rate of incapacitation F pattern spermatozoa converted to capacitation B pattern sperm cell in concentration-dependent manner and mostly increased capacitation B pattern sperm cell and decreased acrosome reaction AR pattern sperm cell in 1mg/ml concentration. When sperm was incubated for 1, 2 and 4h in fertilization medium containing 1mg/ml CS-C, it showed that the capacitated B pattern sperm cell was significantly (p<0.01) increased and the AR pattern sperm cell was significantly decreased at each time point in the presence than in the absence of CS-C. For identifying the validity of CS-C in sperm capacitation, sperm-oocyte was inseminated in fertilization medium containing CS-C (0-2mg/ml) and the rate of fertilized oocytes was examined, which showed that the penetration rates significantly (p<0.05) increased from 0.5 to 1.0mg/ml concentrations (87.4-96.3%) compared with control (74.9%). For identifying the universality of CS-C in sperm capacitation, four different semens (boar S-484, S-454, D-815 and D-748) were incubated in fertilization medium containing CS-C (1mg/ml) for 2h, respectively, which showed that CS-C increased the rate of capacitation B pattern sperm cell and decreased acrosome reaction AR pattern sperm cell in each semen. And it showed that CS-C yielded a higher promote effect (93.9%, 83.9%, 60.7% and 44.9%, respectively) on sperm penetration compared to unaddition control (63.4%, 22.0%, 3.3% and 3.3%, respectively). Sperm-oocyte binding analysis showed that CS-C increased the number of sperm bound to oocyte compared unaddition control in each semen. These results suggested that CS-C is the efficient factor on sperm capacitation in pigs, CS-C may promote sperm from the incapacitated to capacitated state and sequentially prevent sperm from spontaneous acrosome reaction, and thus facilitate the sperm-zona binding and sperm penetration to oocyte.

Production of plasminogen activators (PAs) in bovine cumulus-oocyte complexes during maturation in vitro: effects of epidermal growth factor on production of PAs in oocytes and cumulus cells.

We examined whether plasminogen activators (PAs) are produced by bovine cumulus-oocyte complexes (COCs) during maturation in vitro. The effects of epidermal growth factor (EGF) on production of PAs in oocytes and cumulus cells were also examined. When COCs were cultured for 24 h with 30 ng/ml EGF, three plasminogen-dependent lytic zones (58.5 +/- 3.5 kDa, 79.0 +/- 3.0 kDa, and 113.5 +/- 6.5 kDa) were observed. Addition of amiloride, a competitive inhibitor of urokinase-type PA (uPA), to the zymogram eliminated the activity of the 58.5 +/- 3.5-kDa zone, suggesting that this band is a uPA. However, since the activity of the remaining two bands was not eliminated, it was suggested that the 79.0 +/- 3.0-kDa band is a tissue-type PA (tPA) and the 113.5 +/- 6.5-kDa band is possibly a tPA-PA inhibitor (tPA-PAI) complex. In COCs before culture, however, no activity of PAs was detected. At 6 h of culture, the same level of uPA activity was detected in COCs cultured both in the absence and in the presence of EGF. The uPA activity was increased at 12 h of culture but without further increase at 24 h of culture, with higher activity in the presence than in the absence of EGF. The activity of tPA and tPA-PAI was first detected at 24 h of culture in the absence of EGF. In the presence of EGF, however, some activity of tPA-PAI was detected at 12 h of culture. At 24 h of culture, the activity of all PAs was detected in cumulus cells, but only uPA activity was detected in oocytes, with higher activity in the presence than in the absence of EGF. The uPA activity in oocytes was not detected when they were cultured without cumulus cells in either the presence or absence of EGF, although cumulus expansion was stimulated by EGF, exhibiting a time-course similar to that observed in PA production. These results suggest that uPA, tPA, and tPA-PAI are all produced by bovine COCs, but only uPA by oocytes, during maturation in vitro. However, cumulus cells play an essential role or roles in the production of uPA by oocytes, and EGF enhances the roles of cumulus cells.