Objective To investigate the effects of hypoxia on the transcriptional phenotype and ultrastructure of tumor-associated macrophages(TAMs)in glioma.Methods CD14+monocytes were isolated from healthy human peripheral blood samples collected from the Blood Bank of the First Affiliated Hospital of Army Medical University,and the cells were induced to differentiate into TAMs through co-culture with glioma cell-conditioned medium.Hypoxic TAM models were established using varying concentrations of cobalt chloride hexahydrate(CoCl2,50～400 μmol/L)or hypoxic conditions(1%,5%,10%O2)for 48 h,while normoxic TAM models(21%O2)served as controls.RT-qPCR and transcriptome sequencing were employed to analyze transcriptional changes in TAMs under normoxic and hypoxic conditions.Gene set enrichment analysis(GSEA)was applied to compare the differences in angiogenesis,glycolysis and other hypoxia-responsive pathways between the 2 conditions.Transmission electron microscopy(TEM)or immunofluorescence staining was conducted to assess the ultrastructural alterations in cytoskeleton,endoplasmic reticulum(ER),and mitochondria in normoxic and hypoxic TAMs(1%O2).Results Hypoxic TAMs exhibited up-regulated transcription of hypoxia-responsive markers(oxygen transport,glycolysis,pro-angiogenesis),with the effects correlating with hypoxia severity(P<0.05).GSEA revealed significant up-regulation of hypoxia,angiogenesis regulation,glycolysis and gluconeogenesis,and starvation stress pathways,alongside down-regulation of innate immunity,macrophage activation,cytoskeleton,and protein maturation pathways in hypoxic TAMs(P<0.05).TEM and immunofluorescence staining demonstrated obvious ultrastructure changes,including disrupted cytoskeletal organization,shortened rough ER with reduced ribosomes,mitochondrial swelling with cristae damage,and diminished ER-mitochondria contacts in hypoxic TAMs.Conclusion CoCl2 and hypoxia induce a hypoxic transcriptional phenotype in TAMs,which may potentially associated with ultrastructural remodeling of the cytoskeleton,ER,and mitochondria.

The clinical data of a child with neurodevelopmental disorders caused by a new mutation in the POLR2A gene were retrospectively analyzed.The patient was a 4-year and 2-month-old girl who presented at Xiamen Hospital, Children′s Hospital of Fudan University in June 2024 with clinical manifestations of early infantile hypotonia, muscle atrophy of both lower limbs, global developmental delay (including delays in motor and language development, mental retardation, etc.), sleep difficulties, feeding difficulties, autistic behaviors (namely, social withdrawal), epilepsy, and auditory deficits.The child had one seizure at the age of 2 years and 8 months and one at the age of 4 years, but seizures are currently controlled by drugs.Cranial magnetic resonance imaging and CT showed agenesis of the corpus callosum, bilateral ventricular widening and cerebellar hypoplasia.Whole exome sequencing showed a new mutation c. 3364C>T (p.P1122S) in the POLR2A gene (NM_000937) in the child, and no related gene variants were found in either parental lineage.According to the American College of Medical Genetics and Genomics rating guidelines, it was determined to be a suspected pathogenic variant (PS2+ PM2+ PP3+ PP4).The mutation site has not been reported at home and abroad.The c. 3364C > T ( p. P1122S ) mutation of the POLR2A gene can cause neurodevelopmental disorders, severe phenotypes and poor long-term prognosis.

The clinical data of a child with neurodevelopmental disorders caused by a new mutation in the POLR2A gene were retrospectively analyzed.The patient was a 4-year and 2-month-old girl who presented at Xiamen Hospital, Children′s Hospital of Fudan University in June 2024 with clinical manifestations of early infantile hypotonia, muscle atrophy of both lower limbs, global developmental delay (including delays in motor and language development, mental retardation, etc.), sleep difficulties, feeding difficulties, autistic behaviors (namely, social withdrawal), epilepsy, and auditory deficits.The child had one seizure at the age of 2 years and 8 months and one at the age of 4 years, but seizures are currently controlled by drugs.Cranial magnetic resonance imaging and CT showed agenesis of the corpus callosum, bilateral ventricular widening and cerebellar hypoplasia.Whole exome sequencing showed a new mutation c. 3364C>T (p.P1122S) in the POLR2A gene (NM_000937) in the child, and no related gene variants were found in either parental lineage.According to the American College of Medical Genetics and Genomics rating guidelines, it was determined to be a suspected pathogenic variant (PS2+ PM2+ PP3+ PP4).The mutation site has not been reported at home and abroad.The c. 3364C > T ( p. P1122S ) mutation of the POLR2A gene can cause neurodevelopmental disorders, severe phenotypes and poor long-term prognosis.

Schinzel-Giedion syndrome caused by SETBP1 gene mutation is a rare neurodevelopmental disorder characterized by neurodevelopmental disorders, multi-organ congenital developmental abnormalities (such as skeletal anomalies, urinary and renal malformations, heart defects, etc.), and an increased risk of childhood cancer. The clinical data and diagnosis and treatment process of a patient with Schinzel-Giedion syndrome related neurodevelopmental disorders caused by SETBP1 gene mutation were reported in this article. The clinical characteristics of the disease were analyzed through literature review to improve clinical doctors′ understanding of the disease.

Extracorporeal membrane oxygenation (ECMO) is a technique in which breathing and circulation are supported extracorporeally. Severe trauma may induce cardiopulmonary failure, for which ECMO can play an adjunctive role in the salvage treatment of circulatory and respiratory failure when conventional treatments are ineffective. Bypass with ECMO can rapidly improve the state such as circulatory failure and hypoxemia in critically ill patients in short term and can partially or fully replace their cardiopulmonary function in long term, winning valuable time for normal recovery of cardiopulmonary function. Because of the physical state of severe trauma patients and the ECMO equipment, there are still various complications clinically. Trauma patients show high risk of bleeding, vulnerability to wound infection and probability of combined organ injury and dysfunction, so more comprehensive measures for the prevention and treatment of complications during the use of ECMO therapy are required. The authors review the research progress in complications and corresponding prevention and treatment strategies during ECMO support for severe trauma, aiming to provide a reference to prevent and treat these complications.

Objective:To investigate the clinical phenotype and gene mutation in a child with developmental disorders caused by CTNNB1 gene mutation. Methods:Clinical data of a child with CTNNB1 gene mutation who was admitted to Xiamen Hospital of Fudan University Affiliated Pediatric Hospital in May 2017 were collected, whole exome sequencing technology was applied to verify the family lineage of the child, and the pathogenicity of mutation site was analyzed. Results:The patient was a 6 years and 1 month old male, with a clinical phenotype including mental retardation, motor developmental disorders, speech disorders, visual disorders (internal strabismus), microcephaly, and behavioral problems (social withdrawal, overdependence, etc.), as well as panic syndrome (i.e., sudden shrieking in response to auditory and visual stimuli, extensional rigidity of the body, etc., followed by short periods of general extensional rigidity). The whole exome sequencing results showed the presence of a de novo mutation c.283(exon4)C>T in the CTNNB1 gene, and the c.283(exon4)C>T mutation was interpreted as pathogenic (PVS1+PS2+PS1+PM2+PM) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. No relevant genetic variants were found in the parental family verification. Conclusion:CTNNB1 gene mutation c.283(exon4)C>T can cause neurodevelopmental disorders, including mental retardation, motor developmental disorders, speech disorders, visual disorders, microcephaly and behavioral abnormalities.

Objective: To understand the situation of ticks carrying pathogens in border areas of Heilongjiang province. Methods: From 2009 to 2018, tick specimens were collected in Yichun, Daxing′anling area and Jiamusi in Heilongjiang province. A total of 2 530 ticks were studied, including 800 Ixodes persulcatus and 1 730 Dermacentor silvarum. Tick-borne encephalitis virus (TBEV), severe fever with thrombocytopenia syndrome virus (SFTSV), omsk hemorrhagic fever virus (OHFV), langat virus (LGTV), powassan virus (POWV) were detected by real-time RT-PCR. Spotted fever group rickettsia (SFGR) and Borrelia burgdorferi sensulato (B.b.s.l) were detected by PCR in ticks collected from Jiamusi area. Results: All tick speciments collected were negative for TBEV, SFTSV, OHFV, LGTV and POWV. Tick specimens from Jiamusi carried SFGR and B. b.s.l.with positive rates of 59.5% and 8.9%. Conclusions The ticks in border areas of Heilongjiang province carry spotted fever group rickettsia and Borrelia burgdorferi, and the carrying rate of spotted fever group rickettsia is high. The monitoring and control of ticks and tick-borne diseases should be strengthened.

Epidemiology is a branch of science that mainly involves in the etiology studies of non-randomness phenomenon among homogenous populations. In this paper, we use causal-thinking, supported by its tool-Directed Acyclic Graphs, to illustrate how the estimation of effects is affected by the issues as relations between effect and association, time sequences between variables and their measured counterparts, natural picture of dynamic population, formation of susceptible population, selection of study population, impact of covariates and types of cases etc., on the estimation of effects. This type of thinking may help us to re-capture the epidemiological theories, methods and related applications. Thus, causal-thinking should be strengthened.

Objective: To analyze the epidemiological characteristics and distribution characteristics of tick-borne encephalitis in China in 2014, and to provide scientific basis for formulating specific prevention and control measures. Methods: The epidemic data were obtained from the "infectious disease report information management system" , using Excel 2016, GIS and other software to summarize and analyze the cases of tick borne encephalitis (TBE) reported, using the number of cases, incidence, composition ratio and other indicators to analyze and describe the TBE epidemiological characteristics in China in 2014. Results: In 2014, a total of 322 cases of TBE were reported in 9 provinces in China, with an annual incidence of 0.024/100, 000 and 1 death of patient. The provinces with high number of cases were Jilin province, Inner mongolia autonomous region and Heilongjiang province, and the number of cases in the other six provinces is no more than two. TBE was distributed in spring and summer, and it is concentrated in May to July. The age of the affected population was mostly concentrated in 40-49 years old, the male-female ratio was 1.6∶1 (198/124), and the patients were dominantly farmers, household and unemployed workers, and forestry workers, they accounted for 49.40% (159/322), 26.40% (85/322) and 18.60% (60/322) of the national TBE cases respectively. The three hospitals that reported the most TBE cases in 2014 were Inner mongolia forestry general hospital, Jiangyuan People′s hospital of Baishan city, Jilin province and Mudanjiang forestry central hospital of Heilongjiang province. The number of reported cases in these three hospitals accounted for 68.6% of the whole country. The laboratory diagnosis rate of Inner mongolia forestry general hospital was the highest (91.9%). Conclusions In 2014, the incidence of TBE in China has continued to rise compared with the previous two years. The geographical focus is mainly on the forest areas of Daxing′anling, Xiaoxing′anling and Changbai Mountain.

Objective To investigate the radiosensitization of artesunate on nude mouse transplanted with HeLa cells,and to explore its possible mechanisms.Methods HeLa cells were inoculated into the nude mice to establish tumor model.Mice were randomly divided into 4 groups as blank control,artesunate group,radiation group and artesunate + radiation group when average volume of tumor were about 5 mm × 5 mm× 5 mm.During the term of treatment,the volume of tumors were measured every 2days.After 14 days treatment,the mice were killed and tumor tissues were harvested for flow cytometry to detect the alteration of cell cycle.Meanwhile,the pathological change of the tumor tissue was observed with HE staining method,and the change of expression of cycle regulatory protein Cyclin B1,Cdc2 and Wee1 were detected by Western blot.Results The growth of tumor was significantly inhibited by artesunate combined with radiation and its inhibition rate was 72.34％.Flow cytometry results showed that the percent of cells in G1 phase increased and G2 phase decreased in the artesunate + radiation group compared with those in irradiation group ( t =4.41,4.12,P ＜ 0.05 ).The expression level of Cyclin B1 was obviously increased while that of Wee1 decreased in the artesunate + radiation compared with irradiation group.There was no difference in the expression of Cdc2 among the four groups.Conclusions Artesunate can dramatically increase the radiosensitivity of transplanted tumor of HeLa cells.The possible mechanism might be related to the decreasing G2 phase by regulating the expression of Cyclin B1 and Wee1.