OBJECTIVES: To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms. METHODS: A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR. RESULTS: HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V⁺/PI⁺ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2. CONCLUSIONS DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.
Humans ; Dexmedetomidine/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Heat-Shock Response/drug effects* ; Signal Transduction/drug effects* ; Membrane Potential, Mitochondrial ; Muscle, Skeletal/cytology* ; Heme Oxygenase-1/metabolism* ; Apoptosis/drug effects*

Extracorporeal membrane oxygenation (ECMO) is a key continuous extracorporeal life support technology that can partially or completely replace a patient's cardiopulmonary function, thereby winning valuable time for the diagnosis and treatment of the primary disease. With the widespread application of ECMO, the need for transport has increased. However, during transfers, the standard heater unit is often large and inconvenient to carry, while alternative warming measures tend to be ineffective. This frequently leads to complications such as hypothermia or the inability to maintain body temperature, which can seriously affect the patient's prognosis. In response to this challenge, the medical and nursing staff of the critical care medicine department at Zhongda Hospital Affiliated to Southeast University jointly designed an insulation device for ECMO transport pipelines. The device was successfully granted a National Utility Model Patent of China (patent number: ZL 2021 2 0653569.3). It primarily consists of key components such as a heating pad, velcro straps, a cover layer, a backing layer, an electric heating layer, and a wiring plug. Its advantages include portability, the ability to effectively wrap around and warm the ECMO circuit during transit, and a reduction in the incidence of hypothermia-related complications. Furthermore, its transparent material design allows for real-time monitoring of the ECMO system's status, making it both economical and practical.
Extracorporeal Membrane Oxygenation/instrumentation* ; Humans ; Equipment Design

Objective To observe the value of radiomics models based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced hepatobiliary phase(HBP)MRI for assessing clinical pathological stage of hepatic fibrosis(HF).Methods Data of 240 patients with pathologically/clinically diagnosed and clinical pathological staged HF who underwent Gd-EOB-DTPA enhanced MR examination were retrospectively analyzed.The liver-to-muscle signal intensity ratio(SIR1)and liver-to-spleen signal intensity ratio(SIR2)were measured based on HBP images.Radiomics features of HBP images were extracted and screened to construct radiomics models.The signal intensity ratio(SIR)-radiomics combined models were constructed based on SIR and radiomics signatures.Receiver operating characteristic(ROC)curves were drawn to evaluate the efficacy of each model for assessing clinical pathological stage of HF.Results The area under the curve(AUC)of SIR1 and SIR2 models for assessing clinical pathological stage of HF were 0.63-0.70 and 0.65-0.71,respectively.The most effective radiomics model for assessing HF,significant HF,advanced HF and early cirrhosis was support vector machine(SVM),SVM,light gradient boosting machine and K-nearest neighbor model,respectively,with the AUC in validation set of 0.87,0.82,0.81 and 0.80,respectively,while the AUC of SIR-radiomics combined models in validation set of 0.88,0.82,0.82 and 0.81,respectively.Conclusion The radiomics models based on Gd-EOB-DTPA enhanced HBP MRI were helpful for assessing clinical pathological stage of HF.Combining with HBP SIR could improve their efficacy.

Objective To explore the genetic characteristics of fetuses with congenital heart diseases(CHD)diagnosed by prenatal ultrasound.Methods Data of 613 singletons with prenatal ultrasonic diagnosed CHD were retrospectively analyzed.The cardiac structural abnormalities were classified into 8 types.Whole-exome sequencing(WES)was performed for 40 fetuses since chromosomal karyotyping analysis and/or chromosomal microarray analysis(CMA)showed benign copy number variations(CNV)or variants of uncertain significance(VUS).Results Among 613 fetuses,479 fetuses underwent both chromosomal karyotyping analysis and CMA,genomic abnormalities were detected in 60 fetuses(60/479,12.53％).Among 134 fetuses underwent only CMA,genomic abnormalities were found in 4 fetuses(4/134,2.99％).According to results of chromosomal karyotyping analysis and/or CMA,abnormalities were noticed in 40 fetuses(40/568,7.04％)among 568 fetuses with isolated CHD,while in 15 fetuses(15/45,33.33％)among 45 fetuses with non-isolated CHD,respectively.Abnormality detection rate of chromosomal karyotyping analysis and/or CMA in fetuses with complex CHD(10/41,24.39％)was higher than that in fetuses with non-complex CHD(54/572,9.44％).Among complex CHD fetuses,abnormality detection rate was the highest in fetuses with conotruncal defect(CTD)combined with malformation of venous system(4/13,30.77％),while among fetuses with non-complex CHD,situs inversus viscerum had the highest detection rate(1/4,25.00％).Among 40 fetuses chromosomal karyotyping analysis and/or CMA showed benign CNV or VUS,WES indicated pathogenic CNV/likely pathogenic CNV(P/LP)in 3 fetuses,VUS in 3 fetuses and benign CNV in 34 fetuses.Conclusion Fetuses with CHD,especially extracardiac malformations had possibilities of genomic abnormalities.Fetuses with CTD combined with malformation of venous system had higher possibilities of genomic abnormalities.Compared with CMA alone,chromosomal karyotyping analysis combined with CMA was helpful for detecting genomic abnormalities.

In this paper， we systematically sorted out and verified the name， origin， producing area change， quality， efficacy and processing of Halloysitum Rubrum by consulting materia medica， medical books， prescription books from past dynasties， and modern literature， and combined with the comprehensive analysis of trait identification， hygroscopicity measurement and X-ray diffraction（XRD） detection， in order to provide a basis for understanding the original source of the mineral medicine. The results indicated that Halloysitum Rubrum was first contained in the Shennong Bencaojing， it had been consistently named Chishizhi， there were also aliases such as Chifu， Hongxinshi and Chiyouzhi. The description of Halloysitum Rubrum in ancient materia medica aligns with modern findings， categorizing it under the silicate kaolinite family， specifically polyhydrous kaolinite， with associated minerals mainly being dickite， nacrite， hematite， gibbsite， mica， etc. Historically， the production area of Halloysitum Rubrum was mainly located in the Qinling Mountains， Shandong and Henan， and is now primarily distributed in most parts of China， including Henan， Hubei and other provinces. Quality evaluation in ancient times included descriptions like "fresh and greasy color"， "delicately sticky tongue and lips" and "smooth as fat". Modern materia medica mostly evaluates its quality based on color， luster， texture and hygroscopicity， noting characteristics such as red color， smoothness， delicacy， softness and strong viscosity. Halloysitum Rubrum is sweet， sour and pungent in flavor， warm in nature， non-toxic， and belongs to the heart and large intestine meridians. It acts as an astringent and solidifying agent， particularly useful in the treatment of long-term dysentery and diarrhea， common processing methods include fire calcination， water flying， and vinegar quenching. Comprehensive analysis of the traits， XRD and humidity absorption of different batches of samples showed that the commercially available Halloysitum Rubrum is mainly bright red or brownish red， with a smooth surface like grease， soft and smooth texture， delicate cross-sectional texture， and some have waxy luster and strong water absorption. It is mainly composed of 10 Å（1 Å=0.1 nm） polyhydric kaolinite， and is often accompanied by 7 Å polyhydric kaolinite， nacrite， etc. Genuine products tend to have higher moisture absorption than counterfeit ones， which can be used as a key indicator to distinguish the authenticity. The quality evaluation of Halloysitum Rubrum aligns with historical materia medica， where "fresh color， delicate and greasy lips" could serve as a key feature for its quality evaluation.

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 To investigate the correlation between HLA-DM gene polymorphism and antibody response induced by poliomyelitis vaccine.Methods 355 healthy infants aged 2 to 3 months in Guangxi Zhuang Autonomous Region were selected as the study objects,and 10 SNPs of DMA exon 3 and DMB exon 2/3 were genotyped by Sanger sequencing.The correlation between DMA and DMB genes and poliomyelitis vaccine-induced antibody response was analyzed at allele,genotype and haplotype levels.Results In the type Ⅰ antibody response induced by polio vaccine,the frequencies of DMA*01:02,DMB*01:01,DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group(P<0.05).In the polio type Ⅱ antibody response,the frequencies of DMA*01:02,DMA*01:02/DMA*01:02,DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group(P<0.05).Conclusion Alleles DMA*01:02 and DMB*01:01 may be associated with type Ⅰ and type Ⅱ antibody responses induced by poliomyelitis vaccine.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

Objective:To introduce the method of using anal fistula endoscope to treat chronic sinus tract leakage at rectal anastomosis site.Methods:We used anal fistula endoscopy to treat a patient with chronic sinus tract leakage after radical resection of rectal cancer, mainly including the following 5 steps: (1) establishing a water injection circulation system through the anus; (2) scraping off purulent coating and mucosa on the surface of the sinus tract with the brush; (3) hemostasis and removal of necrotic tissue with electrocoagulation rods; (4) filling the sinus tract with bioprotein gel; (5) compressing the sinus tract with transanal drainage tube.Results:The patient is a 70 year old male with rectal cancer. After undergoing 3D laparoscopic assisted radical resection of rectal cancer via abdominal anterior resection (Dixon's procedure) and diverting ileostomy surgery for more than 3 months, leakage of the rectal anastomosis was found through colonoscopy and anal iodine water contrast imaging .The patient started eating and flowing juice 6 hours after surgery, got out of bed 24 hours after surgery, and was discharged 48 hours after the removal of the anal canal. Three months after surgery, colonoscopy and transanal iodine hydrography showed that the sinus repair was intact. The diverting ileostomy was reduced 4 months after surgery.Conclusion:Anal fistula endoscope is safe and feasible for the treatment of chronic sinus tract anastomotic leakage in selected patients.

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.