Intestinal radiosensitivity makes radiation-induced intestinal injury (RIII) as a common complication among individuals exposed to accidental radiation and patients with abdominal or pelvic malignancies receiving radiotherapy. At present, there are no effective measures for the prevention and treatment of RIII. Developing novel prevention and treatment strategies is of great significance for improving the prognosis and quality of life for both individuals exposed to accidental radiation and cancer patients. Lactobacillus, a Gram-positive bacterium, is widely observed in humans and animals. It exhibits notable probiotic functions, including maintaining gut microbiota homeostasis, preserving intestinal barrier, and modulating immune responses. Substantial studies have demonstrated that Lactobacillus has remarkable protective and therapeutic effects against radiation-induced injury, specifically significantly alleviating RIII. These probiotic functions of Lactobacillus make it have high priority to become the chassis of genetically engineered strains. However, multiple factors influence the construction of a genetically engineered strain, limiting the application of Lactobacillus as a chassis. This review focuses on the probiotic functions of Lactobacillus, highlighting advances in research on Lactobacillus and its engineered probiotics in radiation protection and treatment. Furthermore, it summarizes key factors influencing the construction of genetically engineered strains based on the Lactobacillus chassis. It aims to provide insights for developing genetically engineered strains with radioprotective and therapeutic effects using Lactobacillus as the chassis.

OBJECTIVE: To explore the clinical and genetic characteristics of a child with intellectual development disorder and seizures due to a variant of AP2M1 gene. METHODS: Clinical data of a child with intellectual development disorder and epilepsy who was admitted to the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in January 2021 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected for whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis. The three-dimensional structure of the AP2M1 protein was visualized using Chimera v1.10.1 software. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants from the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). With "AP2M1 gene" "epilepsy" "intellectual disability" as the keywords, relevant cases were searched from CNKI, Wanfang Data knowledge service platform and PubMed databases with the search time spanning from the establishment of the database to September 2024. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2020-57). RESULTS: The child was a 8-years-and-6-months-old boy, who could raise his head at 3 months and sit alone at 8 months old. He could not walk alone at 1 year old and underwent 2 months' rehabilitation treatment, and could walk alone and call his parents at 1-and-a-half-years-old. At 4-years-and-10-months-old, he started to have frequent seizures, manifesting as low level of consciousness, body shaking, accompanied by blinking, lasting about a few seconds several times a day and could be relieved. With the treatment of sodium valproate combined with lamotrigine, the convulsions were controlled, but his movement and cognition were lagged behind. DNA sequencing revealed that he has harbored a novel variant of the AP2M1 gene (NM_004068.3) c.508C>T (p.Arg170Trp). Sanger sequencing confirmed that both of his parents were of the wild-type. According to the guidelines from the American College for Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PS2+PS4+PM1+PM2+PP2+PP3). The difference between the wild-type and mutant AP2M1 proteins can be clearly viewed through its three-dimensional structure. Two previous reports have included 5 cases due to the same variant. Common manifestations have included seizures (100%, 5/5), motor retardation (100%, 5/5), intellectual impairment (100%, 5/5), autism spectrum disorder (60%, 3/5), ataxia (100%, 5/5), and special facial features (20%, 1/5). CONCLUSION The c.508C>T (p.Arg170Trp) variant of the AP2M1 gene may underlie the intellectual retardation and seizure in this child.
Humans ; Male ; Child ; Intellectual Disability/genetics* ; Seizures/genetics* ; Exome Sequencing ; Mutation

Objective To investigate the changes of serum levels of soluble scavenger receptor 163 (sCD163),angiopoietin-like protein 3 (ANGPTL3) before and after intravenous thrombolysis in patients with acute cerebral infarction (ACI) and their correlation with prognosis. Methods A total of 60 ACI patients accepted by Cangzhou Central Hospital from June 2021 to June 2022 were collected as the ACI group,and another 60 healthy individuals were regarded as the control group. According to the National Institutes of Health Stroke Scale (NIHSS) score after admission,60 patients were divided into mild group (n=10),moderate group (n=38) and severe group (n=12).According to the scores on the modified Rankin scale 90 days after thrombolysis,patients were separated into a good prognosis group (n=42) and a poor prognosis group (n=18). The serum levels of sCD163 and ANGPTL3 were detected using enzyme linked immunosorbent assay (ELISA),and receiver operating characteristic (ROC) curve was applied to analyze the predictive value of serum sCD163 and ANGPTL3 levels for the prognosis of ACI patients after intravenous thrombolysis therapy. Results Compared with the control group,the levels of serum sCD163 (687.55±86.43 ng/ml vs 411.07±58.24 ng/ml) and ANGPTL3 (60.28±10.55 mg/L vs 25.34±5.93 mg/L) in ACI group were significantly increased,and the differences were significant (t=20.549,22.363,all P<0.05). The levels of serum sCD163 (551.65±69.66 ng/ml,668.92±81.12 ng/ml,859.79±117.24 ng/ml) and ANGPTL3 (44.52±8.12 mg/L,58.67±10.37 mg/L,75.34±13.12 mg/L) in mild,moderate and severe groups were gradually increased,and the differences were significant (F=36.011,23.007,all P<0.05). Compared with the good prognosis group,the proportion of time from onset to thrombolysis≥ 3 h,the proportion of NIHSS score>10 at admission,and the serum sCD163 and ANGPTL3 levels before and after thrombolysis were significantly increased in the poor prognosis group,and the differences were statistically significant (t/x2=5.644,4.775,8.982,10.866,10.293,9.702,all P<0.05). ROC results showed that the area under the curves(95％ confidence intervals)[AUC(95％CI)]of serum sCD163 and ANGPTL3 level alone in predicting the prognosis of ACI patients were 0.830 (0.711～0.915) and 0.783 (0.658～0.879),and their sensitivity and specificity were 72.22％ and 85.71％,77.78％ and 85.71％,respectively. The AUC(95％CI)of combined prediction of serum sCD163 and ANGPTL3 in predicting the prognosis of ACI patients[0.950(0.861～0.990)]was obviously greater than the AUC predicted by sCD163 and ANGPTL3 alone (Z=2.378,2.109,P=0.017,0.035). Conclusion sCD163 and ANGPTL3 levels are elevated in the serum of ACI patients,and are related to their severity and prognosis.

Intestinal radiosensitivity makes radiation-induced intestinal injury (RIII) as a common complication among individuals exposed to accidental radiation and patients with abdominal or pelvic malignancies receiving radiotherapy. At present, there are no effective measures for the prevention and treatment of RIII. Developing novel prevention and treatment strategies is of great significance for improving the prognosis and quality of life for both individuals exposed to accidental radiation and cancer patients. Lactobacillus, a Gram-positive bacterium, is widely observed in humans and animals. It exhibits notable probiotic functions, including maintaining gut microbiota homeostasis, preserving intestinal barrier, and modulating immune responses. Substantial studies have demonstrated that Lactobacillus has remarkable protective and therapeutic effects against radiation-induced injury, specifically significantly alleviating RIII. These probiotic functions of Lactobacillus make it have high priority to become the chassis of genetically engineered strains. However, multiple factors influence the construction of a genetically engineered strain, limiting the application of Lactobacillus as a chassis. This review focuses on the probiotic functions of Lactobacillus, highlighting advances in research on Lactobacillus and its engineered probiotics in radiation protection and treatment. Furthermore, it summarizes key factors influencing the construction of genetically engineered strains based on the Lactobacillus chassis. It aims to provide insights for developing genetically engineered strains with radioprotective and therapeutic effects using Lactobacillus as the chassis.

Objective To investigate the changes of serum levels of soluble scavenger receptor 163 (sCD163),angiopoietin-like protein 3 (ANGPTL3) before and after intravenous thrombolysis in patients with acute cerebral infarction (ACI) and their correlation with prognosis. Methods A total of 60 ACI patients accepted by Cangzhou Central Hospital from June 2021 to June 2022 were collected as the ACI group,and another 60 healthy individuals were regarded as the control group. According to the National Institutes of Health Stroke Scale (NIHSS) score after admission,60 patients were divided into mild group (n=10),moderate group (n=38) and severe group (n=12).According to the scores on the modified Rankin scale 90 days after thrombolysis,patients were separated into a good prognosis group (n=42) and a poor prognosis group (n=18). The serum levels of sCD163 and ANGPTL3 were detected using enzyme linked immunosorbent assay (ELISA),and receiver operating characteristic (ROC) curve was applied to analyze the predictive value of serum sCD163 and ANGPTL3 levels for the prognosis of ACI patients after intravenous thrombolysis therapy. Results Compared with the control group,the levels of serum sCD163 (687.55±86.43 ng/ml vs 411.07±58.24 ng/ml) and ANGPTL3 (60.28±10.55 mg/L vs 25.34±5.93 mg/L) in ACI group were significantly increased,and the differences were significant (t=20.549,22.363,all P<0.05). The levels of serum sCD163 (551.65±69.66 ng/ml,668.92±81.12 ng/ml,859.79±117.24 ng/ml) and ANGPTL3 (44.52±8.12 mg/L,58.67±10.37 mg/L,75.34±13.12 mg/L) in mild,moderate and severe groups were gradually increased,and the differences were significant (F=36.011,23.007,all P<0.05). Compared with the good prognosis group,the proportion of time from onset to thrombolysis≥ 3 h,the proportion of NIHSS score>10 at admission,and the serum sCD163 and ANGPTL3 levels before and after thrombolysis were significantly increased in the poor prognosis group,and the differences were statistically significant (t/x2=5.644,4.775,8.982,10.866,10.293,9.702,all P<0.05). ROC results showed that the area under the curves(95％ confidence intervals)[AUC(95％CI)]of serum sCD163 and ANGPTL3 level alone in predicting the prognosis of ACI patients were 0.830 (0.711～0.915) and 0.783 (0.658～0.879),and their sensitivity and specificity were 72.22％ and 85.71％,77.78％ and 85.71％,respectively. The AUC(95％CI)of combined prediction of serum sCD163 and ANGPTL3 in predicting the prognosis of ACI patients[0.950(0.861～0.990)]was obviously greater than the AUC predicted by sCD163 and ANGPTL3 alone (Z=2.378,2.109,P=0.017,0.035). Conclusion sCD163 and ANGPTL3 levels are elevated in the serum of ACI patients,and are related to their severity and prognosis.

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.