Extracorporeal membrane oxygenation (ECMO) is an important treatment for extracorporeal cardiopulmonary life support for clinically critical patients. Currently, ECMO tubing is commonly fixed by tie-wraps or tourniquets, which have shortcomings such as easy loosening and potential damage to the tubing. Improper fixation of the catheter can lead to a series of adverse events, such as accidental disconnection of the tubing, rupture of the tubing, tubing folding, and air ingress into the tubing. In order to overcome the above problems, the research team of Zhongda Hospital, Southeast University invented a device for ECMO line fixation and obtained a national utility model patent of China (patent number: ZL 2019 2 2282849.3). The tool is mainly composed of several devices, including a line fixation clamp, a clip fixation device, and a base plate, which is uniquely designed and easy to operate. During ECMO therapy, this device ensures effective stabilization of the ECMO tubing, preventing unexpected incidents due to catheter loosening and facilitating the observation of ECMO catheter insertion markings. Pipeline can be effectively fixed to avoid the occurrence of accidents due to the loosening of the catheter, and at the same time, it is convenient to observe the placement scale of the ECMO catheter. The novelty and uniqueness of the fixation device materials also effectively prevent the occurrence of pressure injuries during its use.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Objective: To understand the potential categories of harmful behaviors of college students in Wuling Mountain Area and its relationship with campus bullying, so as to provide a theoretical basis for promoting the development of college students physical and mental health. Methods: The stratified random cluster sampling method was used to select 3 042 college students from six universities in Wuling Mountain Area from October to December, 2022. The "Chinese Youth Health Related/Risk Behaviors Questionnaire" (University Edition) compiled by the National Youth Health Related/Risk Behaviors Survey Group was used to investigate the health risk behaviors. The potential category analysis method was used to analyze the food preference, insecurity, fighting, loneliness, depression, insomnia, heartbreak, suicidal ideation, smoking, drinking, game addiction, Internet addiction of health risk behaviors were used to further analyze the relationship between different categories and campus bullying by using multi category Logistic regression method. Results: College students in Wuling Mountain Area were classified into low risk group of category 1 (44.2%), category 2 (5.4%) substance dependent group, category 3(50.4%) emotional disorder group. The distribution of potential categories of health risk behaviors among college students was statistically significant by gender( χ 2=31.44, 11.69， P < 0.05 ). Logistic regression analysis showed that after controlling demographic variables, campus bullying was the risk factor of category 3 emotional disorder group( OR =1.88, P <0.01). Conclusion bullying. Colleges and universities should attach great importance to the occurrence of campus bullying, formulate intervention programs for different categories of health hazard behaviors, and promote the healthy development of college students physical and mental health.

【Objective】 To investigate the effects of biomimetic bone trabecular with the same porosity and pore size and regular porous structure on the adhesion, proliferation, and differentiation of osteoblasts, so as to provide theoretical basis for the improvement of osseointegration performance of titanium alloy implants. 【Methods】 The biomimetic bone trabecular and regular porous structures with the same porosity and pore size were generated by computer-aided software, and then processed into disc-shaped Ti6Al4V scaffolds with a diameter of 10 mm and a height of 3 mm by selective laser melting technology. MC3T3-E1 cells, the precursor cells of mouse osteoblasts in the logarithmic growth phase, were seeded on two kinds of scaffolds and divided into biomimetic bone trabecular group and regular porous structure group. After 3 hours of culture, acridine orange staining and phalloidin /DAPI staining were used to evaluate the number of cell adhesion. After 3 days of culture, the scaffolds were examined by scanning electron microscopy to evaluate the adhesion state of cells. After 1, 3, and 5 days of culture, the scaffolds were taken for CCK8 detection to observe the proliferation of cells. After 7 and 14 days of differentiation, alkaline phosphatase (ALP) activity was detected. After 14 days of differentiation, the expressions of osteogenesis-related genes (ALP, OCN, RUNX2) were detected by RT-PCR. After 30 days of differentiation, the scaffolds were stained with alizarin red and 100 g/L cetylpyridinium chloride was used to dissolve mineralized nodules. Calcium salt deposition was qualitatively and quantitatively detected to evaluate cell differentiation. 【Results】 The results of acridine orange and phalloidin /DAPI staining showed that the biomimetic trabecular Ti6Al4V scaffold adhered to more MC3T3-E1 cells than the regular porous structure, and the cytoskeleton of the former scaffold was more densely distributed. The results of scanning electron microscopy showed that the pseudopodia of MC3T3-E1 cells on the biomimetic bone trabecular Ti6Al4V scaffold were longer and the extension state was better than that of the regular porous structure. CCK8 test showed that the proliferation of MC3T3-E1 cells on the biomimetic trabecular bone titanium alloy scaffold was significantly higher than that on the regular porous structure on the 3rd and 5th day, and the difference gradually increased with the increase of time, with statistical significance (P<0.05). The results of cell differentiation test showed that ALP activity on the bionic trabecular scaffold was higher than that on the regular porous structure (P<0.05). The expressions of osteogenic genes (ALP, OCN, RUNX2) in MC3T3-E1 cells on the biomimetic bone trabecular titanium alloy scaffold were significantly higher than those on the regular porous structure (P<0.05). After 30 days of induction, the amount of calcium salt deposited in the bionic trabecular titanium alloy scaffold was significantly larger than that in the regular porous structure (P<0.05). 【Conclusion】 The biomimetic bone trabecular with a porosity of 65% and an equivalent pore size of 600 μm is more conducive to the adhesion, proliferation and differentiation of mouse osteoblast precursor cells MC3T3-E1 on the titanium alloy scaffold than the regular porous structure with the same porosity and pore size. It is theoretically more conducive to improving the osseointegration performance of titanium alloy implants.

Melorheostosis is a rare disorder of osteopathia. The clinical characteristics of melorheostosis in children is totally different from that in adults. The radiographic features of melorheostosis include the hyperostosis in endosteal on the one side of the cavum medullare and formed streakiness. The soft tissue contracture of the limb and joint deformities are the symptoms of melorheostosis. Here, the authors reported a melorheostosis case of 6 years old girl who suffered from severe valgus deformity of the right knee with permanent patellar dislocation. A surgical stabilization was applied with lateral soft tissue release, medial soft tissue stabilization and transferred the vastus medialis laterally (kinetic stability). After 19 years follow up postoperatively, the limb developed well in satisfied alignment with good function of knee joints, even participated in some sports activities. Other authors reported a similar case of melorheostosis with surgical treatment and achieved good outcomes in limb realignment and reduction. The further suggested that the surgical treatment should be produced before epiphyseal closure.