Objective:To explore the clinical and genetic characteristics of asparagine synthase deficiency.Methods:Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed.Results:All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor.Conclusions:Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Objective:To explore the clinical and genetic characteristics of two children with Neurodevelopmental disorders (NDDs) due to variants of TANC2 gene. Methods:Clinical data of two children who were admitted to the Third Affiliated Hospital of Zhengzhou University respectively in April 2020 and April 2021 were retrospectively analyzed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. By using " TANC2 gene", "Neurodevelopmental disorders", "Nervous system development disorders", " TANC2" as the key words, similar cases were searched from the CNKI, Wanfang database platform and PubMed database, with the search time set as from the establishment of the database to December 2023. This study was approved by Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No. 2020-57). Results:Case 1 was a 1-year-and-3-month-old girl who had developed convulsions at 1 year old and had three episodes of seizures. Her epilepsy had resolved with the treatment of oxcarbazepine, which was stopped at the age of 2-year-and-7-month. Her language, movement and intelligence development were all normal. Case 2 was a 1-year-and-10-month-old boy, who had developed convulsions at 1 year old. His seizure type was myoclonus, and the frequency was dozens of times a day. His epilepsy had resolved with the treatment of sodium valproate. His language, movement and intelligence development was delayed for about half a year. Genetic analysis showed that both children had harbored novel variants of the TANC2 gene (NM_025185.4), including c. 3398G>A (p.Gly1133Glu) and c.2829+ 1G>A, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the former was rated as likely pathogenic (PS2+ PM2_Supporting+ PP3) and the latter was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Two previous reports were retrieved, which had involved 17 cases and 16 variants. Common features had included autism spectrum disorder (70.6%, 12/17), intellectual disability (94.1%, 16/17), language and motor retardation (88.2%, 15/17; 58.8%, 10/17), facial dysmorphism, epilepsy, ataxia, and thoracic and spinal deformities. Conclusion:Variants of the TANC2 gene probably underlay the epilepsy and development delay in these children with NDDs.

Objective:To review the funding status of the National Natural Science Foundation of China in the field of preventive medicine, summarize the characteristics of approved funding for sub-disciplines and institutions, to further analyze the effects of funding distribution.Methods:Descriptively analyze the funding status of the National Natural Science Foundation of China in the field of preventive medicine from 2010 to 2019, and analyze its aggregation effect by constructing a single funding strength and intensity index.Results:The project number, funding amount and number of research institutions have shown an overall upward trend. In the past 10 years, a total of 1.683 billion has been approved for funding, and the proportion in the Department of Health Sciences has remained at about 4%. Non-communicable disease epidemiology, human nutrition, and health toxicology are among the top three in terms of project number, funding amount, and number of grantee institutions. Sub-discipline funding is uneven, showing a phenomenon of development differentiation. The amount of approved funding, the number of institutions, and the strength of individual funding for universities are significantly higher than those of scientific research institutions and CDCs. The total amount of Top 10 funding accounted for 41.49%, which obviously showed a " head" effect.Conclusions:The Natural Science Foundation of China should continue to increase investment in the field of preventive medicine. Key breakthroughs in dominant disciplines, weaker disciplines make up for shortcomings, guide universities, research institutes, and CDCs to carry out inter-institutional project cooperation based on their respective advantages, and encourage interdisciplinary research to enhance discipline innovation capabilities.

Recently, World Health Organization/International Agency for Research on Cancer (WHO/IARC) published the World Cancer Report 2020. This report described the cancer burden of the world, the risk factors of cancer, biological process in cancer development and the prevention strategies of cancer. Based on current status of China’s cancer burden and prevention strategies, this paper briefly interpreted the key points of cancer prevention and control in the report.

Objective:To evaluate the performance of high risk human papilloma virus (HR-HPV) E6/E7 mRNA in triaging women with atypical squamous cells of undetermined signification (ASCUS).Methods:The ASCUS cohort determined by liquid-based cytology test in the cervical cancer screening queue in Luoshan County, Xinyang City, Henan Province 2017 were selected. The population underwent colposcopy biopsy and pathological tests, combined with HPV16 or 18 (HPV16/18), HR-HPV DNA and HPV E6/E7 mRNA test. By using the pathological result as the gold standard, the sensitivity, specificity, positive predictor (PPV), negative prediction (NPV), referral rate and 95% confident interval ( CI) of HPV E6/E7 mRNA, HR-HPV DNA, HPV16/18 were calculated, respectively. Results:The average age of 312 ASCUS women was 52.6±7.3 years old. Among the 290 women diagnosed as normal by pathology, 64 (22.1%) were HPV E6/E7 mRNA positive, 86 (29.7%) were HR-HPV DNA positive, and 19 (6.6%) were HPV16/18 positive. All of the cervical intraepithelial neoplasia (CIN) cases determined by pathology were both HPV E6/E7 mRNA and HR-HPV DNA positive. The sensitivity, specificity, PPV, NPV and referral rate of HPV E6/E7 mRNA for predicting CIN2+ lesion in women with ASCUS were 100.0% (95% CI: 72.3, 100.0), 77.8% (95% CI: 72.8, 82.1), 13.0% (95% CI: 7.2, 22.3), 100.0% (95% CI: 98.4, 100.0) and 24.7%. Compared with HPV E6/E7 mRNA, the sensitivity of HR-HPV DNA was similar with HPV E6/E7 mRNA, but with a lower specificity [70.2% (95% CI: 64.8, 75.1), P<0.05], a higher referral rate (32.1%, P<0.05); while HPV 16/18 had a high specificity (93.4%, 95% CI: 90.0, 95.7) and a low sensitivity (30.0%, 95% CI: 10.8, 60.3). Based on the age stratification by age 45, the sensitivity of HPV E6/E7 mRNA in both age groups was 100.0%. The specificity of HPV E6/E7 mRNA in group of ≥45 years was a little higher than that in group of <45 years [79.0% (95% CI: 73.7, 83.5) versus 68.3% (95% CI: 53.0, 80.4)], but the difference was not statistically significant ( P>0.05). Conclusions:The ASCUS woman triaging effect of HPV E6/E7 mRNA detection is better than those of HR-HPV and HPV16/18 under certain conditions. The application of HPV E6/E7 mRNA detection to triage ASCUS population can avoid unnecessary colposcopy referral and reduce the missed diagnosis of cervical lesions.

Objective:To evaluate the performance of high risk human papilloma virus (HR-HPV) E6/E7 mRNA in triaging women with atypical squamous cells of undetermined signification (ASCUS).Methods:The ASCUS cohort determined by liquid-based cytology test in the cervical cancer screening queue in Luoshan County, Xinyang City, Henan Province 2017 were selected. The population underwent colposcopy biopsy and pathological tests, combined with HPV16 or 18 (HPV16/18), HR-HPV DNA and HPV E6/E7 mRNA test. By using the pathological result as the gold standard, the sensitivity, specificity, positive predictor (PPV), negative prediction (NPV), referral rate and 95% confident interval ( CI) of HPV E6/E7 mRNA, HR-HPV DNA, HPV16/18 were calculated, respectively. Results:The average age of 312 ASCUS women was 52.6±7.3 years old. Among the 290 women diagnosed as normal by pathology, 64 (22.1%) were HPV E6/E7 mRNA positive, 86 (29.7%) were HR-HPV DNA positive, and 19 (6.6%) were HPV16/18 positive. All of the cervical intraepithelial neoplasia (CIN) cases determined by pathology were both HPV E6/E7 mRNA and HR-HPV DNA positive. The sensitivity, specificity, PPV, NPV and referral rate of HPV E6/E7 mRNA for predicting CIN2+ lesion in women with ASCUS were 100.0% (95% CI: 72.3, 100.0), 77.8% (95% CI: 72.8, 82.1), 13.0% (95% CI: 7.2, 22.3), 100.0% (95% CI: 98.4, 100.0) and 24.7%. Compared with HPV E6/E7 mRNA, the sensitivity of HR-HPV DNA was similar with HPV E6/E7 mRNA, but with a lower specificity [70.2% (95% CI: 64.8, 75.1), P<0.05], a higher referral rate (32.1%, P<0.05); while HPV 16/18 had a high specificity (93.4%, 95% CI: 90.0, 95.7) and a low sensitivity (30.0%, 95% CI: 10.8, 60.3). Based on the age stratification by age 45, the sensitivity of HPV E6/E7 mRNA in both age groups was 100.0%. The specificity of HPV E6/E7 mRNA in group of ≥45 years was a little higher than that in group of <45 years [79.0% (95% CI: 73.7, 83.5) versus 68.3% (95% CI: 53.0, 80.4)], but the difference was not statistically significant ( P>0.05). Conclusions:The ASCUS woman triaging effect of HPV E6/E7 mRNA detection is better than those of HR-HPV and HPV16/18 under certain conditions. The application of HPV E6/E7 mRNA detection to triage ASCUS population can avoid unnecessary colposcopy referral and reduce the missed diagnosis of cervical lesions.

Objective: This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining for triage high risk HPV (HR-HPV) infected women. Method: Target objects were women who infected HR-HPV and received colposcopy examination between April and December of 2016 at the Second Affiliated Hospital of Zhengzhou University. Gynecologists collected the cervical exfoliated cells from eligible women for p16/Ki-67 dual staining, LBC testing and HPV DNA testing. Histology diagnosis were used as gold standard. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs) of p16/Ki-67 dual staining, LBC testing and HPV16/18 testing for triage of HR-HPV positive population were calculated and compared. Results: A total of 295 HR-HPV infected women were selected, and the mean age was (44.29±11.48) years old. Positive rates of p16/Ki-67 dual staining, HPV16/18 testing and LBC testing were 70.17% (207), 56.95% (168) and 85.76% (253), respectively. When CIN2+as the endpoint, among the three triage methods, sensitivity of p16/Ki-67 dual staining was 90.00% (95%CI: 85.06%-93.43%), higher than the value of HPV 16/18 testing, but lower than the value of LBC testing. Specificity, PPV and NPV of p16/Ki-67 dual staining were the highest [71.58% (95%CI: 61.81%-79.67%), 86.96% (95%CI:81.69%-90.88%) and 77.27% (95%CI: 67.49%-84.78%)]. When detection for CIN3+, sensitivity of p16/Ki-67 dual staining was 92.90% (95%CI: 87.74%-95.99%), lower than the value of LBC testing, but higher than the value of HPV16/18 testing. Specificity of p16/Ki-67 dual staining was 55.00% (95%CI: 46.74%-63.00%), lower than the value of HPV16/18 testing, but higher than the value of LBC testing. PPV of p16/Ki-67 dual staining was 69.57% (95%CI: 62.99%-75.43%), lower than the value of HPV 16/18 testing, but higher than the value of LBC testing. NPV of p16/Ki-67 dual staining was 87.50% (95%CI: 78.99%-92.87%), higher than value of HPV 16/18 testing, but lower than the value of LBC testing. Conclusion p16/Ki-67 dual staining has better clinical effects than HPV 16/18 testing and LBC testing for triage women with HR-HPV infection.

Objective: To investigate the changes and clinical significance of Caveolin-1, matrix metalloproteinase-9(MMP-9) and interleukin-1β(IL-1β)in cerebrospinal fluid of children with bacterial meningitis or viral encephalitis. Methods: Thirty-six cases of children with bacterial meningitis, 42 cases of children with viral encephalitis, and 20 cases of children with non-nervous system infection were selected from September 2016 to June 2018 at the Third Affiliated Hospital of Zhengzhou University.The levels of Caveolin-1, MMP-9 and IL-1β in cerebrospinal fluid were detected by using enzyme linked immunosorbent assay(ELISA). Results: Cerebrospinal fluid Caveolin-1, MMP-9 , IL-1β levels in the acute phase of bacterial meningitis were(49.06±8.96) ng/L, (134.79±18.88) μg/L, (100.02±14.67) μg/L, respectively, and (29.13±7.25) ng/L, (18.69±7.23) μg/L, (47.57±8.95) μg/L in recovery phase, which were higher than those of the controls[(11.18±2.24) ng/L, (11.53±3.54) μg/L, (39.75±7.08) μg/L)], and the differences were significant (all P<0.05). Cerebrospinal fluid Caveolin-1, MMP-9, IL-1β levels in the acute phase of viral encephalitis were (42.71±10.48) ng/L, (62.78±17.39) μg/L, (57.97±11.28) μg/L, respectively, and (29.13±7.25) ng/L, (18.69±7.23) μg/L, (47.57±8.95) μg/L in recovery phase, which were higher than those of controls, and the differences were significant (all P<0.05). The levels of Caveolin-1, MMP-9 and IL-1β in cerebrospinal fluid of bacterial meningitis group and viral encephalitis group were significantly higher than those of convalescent group (all P<0.05). The levels of Caveolin-1, MMP-9, IL-1β in cerebrospinal fluid of bacterial meningitis group were significantly higher than those in viral encephalitis group (all P<0.05) in the acute phase, and no significant difference was found in the recovery phase(all P>0.05). Cerebrospinal fluid Caveolin-1, MMP-9, IL-1β showed no significant difference among children with different severity of intracranial infection.Correlation analysis showed that there was a positive correlation between Caveolin-1, MMP-9 and IL-1 β levels in cerebrospinal fluid of acute in bacterial meningitis group and viral encephalitis group(Caveolin-1 and MMP-9: R²=0.239, P<0.05; MMP-9 and IL-1β: R²=0.766, P<0.01; Caveolin-1 and IL-1β: R²=0.245, P<0.05). Conclusions Caveolin-1, MMP-9 and IL-1 β involved in the pathogenesis of intracranial infection in children, and the effects of different pathogens on intracranial infection were different.

Objective: To investigate the changes and clinical significance of vascular endothelial (VE)-cadherin and procalcitonin (PCT) in serum and cerebrospinal fluid (CSF) of children with viral encephalitis or bacterial meningitis(BM). Methods: A total of 42 cases of children with viral encephalitis(viral encephalitis group), 36 cases of children with BM(BM group), and 20 cases of children with non-nervous system injury(control group) were selected from September 2016 to June 2018 at the Third Hospital of Zhengzhou University.The serum and CSF levels of VE-cadherin and PCT levels of the 3 groups were detected by using enzyme-linked immunosorbent assay. Results: The levels of VE-cadherin in the serum of viral encephalitis group, BM group and control group at the acute phase were (5.60±1.17) mg/L, (7.08±1.01) mg/L and (2.52±0.68) mg/L respectively, and the levels of VE-cadherin in CSF of viral encephalitis group, BM group and control group were (6.00±1.09) mg/L, (6.97±1.11) mg/L and(1.93±0.88) mg/L, respectively.The levels of PCT in the serum of viral encephalitis group, BM group and control group at the acute phase were (0.26±0.11) μg/L, (0.82±0.17) μg/L and (0.27±0.13) μg/L, respectively, and the levels of PCT in the CSF of viral encephalitis group, BM group and control group were (0.25±0.11) μg/L, (0.72±0.14) μg/L, (0.28±0.17) μg/L, respectively.As a result, the levels of VE-cadherin and PCT in the serum and CSF of BM group showed significant increase, compared with viral encephalitis group and control group in the acute phase(F=124.94, 163.21, 151.62, 127.37, all P<0.01). The levels of VE-cadherin in the serum and CSF of viral encephalitis group were also significantly higher than that of control group (all P<0.01), but there was no difference between viral encephalitis group and control group about the levels of PCT in the serum and CSF (all P>0.05). The levels of VE-cadherin in the serum of viral encephalitis group and BM group after treatment were (2.34±0.81) mg/L and (2.67±1.29) mg/L, and were(2.55±0.92) mg/L and(2.39±0.74) mg/L in the CSF.The levels of PCT in the serum of viral encephalitis group and BM group after treatment were (0.25±0.11) μg/L, (0.30±0.17) μg/L, and the levels of PCT in the CSF of viral encephalitis group and BM group were(0.22±0.10) μg/L and (0.27±0.12) μg/L.After effective treatment, the levels of VE-cadherin, PCT in serum and CSF of BM group and viral encephalitis group were almost equal, and the difference was not statistically significant(F=1.83, 0.76, 2.72, 3.89, all P>0.05). In the receiver operating characteristic (ROC) curve, the area under the ROC curve of VE-cadherin in serum and CSF was 0.896 and 0.912, and was 0.670 and 0.668 of PCT respectively. Conclusions VE-cadherin may be involved in the early stage of intracranial infection, and it may be helpful in differentiation of virus or bacterial infection with PCT.VE-cadherin has a good diagnostic value for intracranial infection.

Objective: To evaluate the performance of high risk human papillomavirus (HR-HPV) DNA test for triage ASC-US in Chinese population. Methods: The study population was from Jiyuan city in Henan Province where a cervical cancer screening cohort (4 026 women) was set up from April to July in 2017. Women with ASC-US and complete recall information of colposcope were selected as the study objects. Self-designed questionnaire was used to survey the general information and medical history of cervical cancer, thencervical cytological speciments were collected for cytodiagnosis and HPV DNA test, followed by colposcopy, lesion biopsy and histology diagnose. The diagnosis of histology was used as the gold standard. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) as well as corresponding 95% confidential interval (CI) were calculated. Results: The average age of the included 393 women with ASC-US were (50.81±9.22) years old. The positivity of high risk human papillomavirus (HR-HPV), HPV16 and HPV18 were 35.6%, 10.69% and 2.80%, respectively. The sensitivity, specificity, PPV and NPV for HR-HPV to detect CIN2+ were 84.38% (68.25%-93.14%), 68.70% (63.74%-73.26%), 19.29% (13.61%-26.61%) and 98.02% (95.46%-99.15%). When compared with HR-HPV, HPV16/18 had a lower sensitivity (59.38% (42.26%-74.48%)) and a higher specificity(91.14% (87.75%-93.65%)), the PPV and NPV were 59.38% (25.32%-50.98%) and 91.14% (93.61%-97.77%). Conclusion It was more effective for HR-HPV to triage ASC-US than HPV16/18. In order to improve the effect of HPV16/18, it should include more HR-HPV types which were more prevalent in Chinese population.