Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

Objective To explore the application of failure mode and effect analysis(FMEA)to analyze the risk status of antitumor drugs in pharmacy intravenous admixture services(PIVAS),implement preventive measures,and to improve the drug safety.Methods FMEA method was used to analyze the risks of different failure modes in the management of antitumor drugs in PIVAS of Wuhu First People's Hospital,and the risk priority value(RPN)scores were calculated respectively.Taking RPN≥216 points as the medium and high risk points,effective preventive measures were taken for them,and the effects before and after the implementation of preventive measures were observed.Results After comprehensive analysis,8 medium and high risk points were identified,including failure to carefully check the returned drugs,insufficient identification of drugs,failure to strictly implement the verification system,mixing of drugs before complete dissolution,incompatibility,wrong placement of drugs,failure to check and seal non-whole drugs by two people,and incorrect verification process.After the preventive measures were taken,the RPN score of the medium and high risk points of the 8 items before implementation was(271.88±33.97)points,the RPN score of the medium and high risk points of the 8 items after implementation was(76.25±28.38)points and there was a statistical difference between them(P<0.05).Compared with before implementation of preventive measures,deployment error rate after implementation was lower(P<0.05).Conclusion FMEA method can effectively prevent risks and reduce the error rate of anti-tumor drug dispensing,thus ensuring the safety of medical staff and patients.

With the continuous improvement of medical information and intelligence, multi-modal data fusion technology is increasingly widely used in the medical field. Multi-modal data not only has a large quantity, but also has rich information content, which can provide strong support for clinical nursing decision-making. However, due to the uneven level of informatization and intelligence development among medical institutions, the development and application of nursing decision support system is still in a fragmented state. Based on this, this study explores in depth the current application status and challenges faced by multi-modal data fusion in nursing decision support systems, with the aim of providing reference for the design and improvement of nursing decision support system at all levels of medical institutions in the future.

A case of paraneoplastic cerebellar ataxia syndrome caused by immune checkpoint inhibitors(ICI)was treated with ofatumumab(OFA).The patient is a 57-year-old male.He used"Camrelizumab"immunotherapy for his previous history of small cell lung cancer.The main reason was"walking unsteadily for more than one year and shaking his head involuntarily for more than one month".After admission,the head MRI,chest CT,electroencephalogram,lumbar puncture and other related examinations were improved.The antibody spectrum of paraneoplastic neurological syndrome was anti-GAD65 antibody IgG(+),and the case was then diagnosed as the immune checkpoint inhibitor-related paraneoplastic neurological syndromes(PNS)of nervous system.After OFA treatment(20 mg/time),the symptoms were obviously improved.This paper analyzes the clinical features and diagnosis and treatment approaches of this case,in order to improve clinicians'understanding of the disease and provide reference for clinical diagnosis and treatment of similar cases.

The pathogens were isolated and purified from the stomach,jejunum and rectum tissues of a Yunnan snub-nosed monkey who died of vomiting,oral and nasal chyme,and abdominal dis-tension,and the species and biological characteristics of the pathogens were studied by biochemical identification,PCR identification,drug susceptibility test,pathogenicity test,serotype identifica-tion,and drug resistance gene and virulence gene analysis.The results showed that the pathogens i-solated from stomach,jejunum and rectum were Escherichia coli(E.coli)serotype O127,belong-ing to enteropathogenic E.coli.They were resistant to cefoxitin and sensitive to gentamicin,gati-floxacin and ciprofloxacin.All the three strains carried drug resistance genes blaTEM and blaCTX-M and virulence genes opmA and opmC.This study provides reference and data support for the prevention and control of enteritis caused by E.coli in Yunnan snub-nosed monkey.

Gait deficits and balance disturbances are prevalent clinical features in Parkinson′s disease (PD). There is an increasing body of evidence pointing towards the degeneration of central cholinergic neurons as a crucial factor leading to these disturbances in PD. This paper presents a comprehensive review of the relevant research on the involvement of the central cholinergic system in the mechanisms underlying gait deficits and balance disturbance in PD. The aim is to provide new perspectives and insights for the treatment of gait deficits and balance disturbances in PD.

Objective:To investigate the regulatory effects of acupuncture and moxibustion on chromatin remodeling complex core catalytic subunit of Brahma-related gene 1(Brg1),histone deacetylase(HDAC)3,HDAC9,and males absent on the first(MOF)in the colon tissue of rats with Crohn disease(CD). Methods:Using the random number table method,60 male Sprague-Dawley rats were divided into 5 groups,including a normal group,a model group,an acupuncture group,a medicinal cake-insulated moxibustion group,and an acupuncture-moxibustion group,with 12 rats in each group.CD rat models were prepared using 2,4,6-trinitrobenzene sulfonic acid(TNBS)in all groups except the normal group.The normal and model groups received no interventions.In the acupuncture group,rats were intervened with acupuncture at bilateral Zusanli(ST36)and Shangjuxu(ST37),20 min/session,once a day.The medicinal cake-insulated moxibustion group received medicinal cake-insulated moxibustion at Qihai(CV6)and bilateral Tianshu(ST25)with 2 cones per point per session,once a day.The acupuncture-moxibustion group received both acupuncture and moxibustion interventions simultaneously.Each intervention was performed for 10 consecutive days.Observations included general condition,disease activity,macroscopic damage,and pathological changes in the rat's colon tissue.Real-time fluorescence quantitative polymerase chain reaction was used to measure the mRNA expression of chromatin remodeling-related enzymes Brg1,HDAC3,and HDAC9,while Western blotting detected the protein expression of Brg1,HDAC3,HDAC9,and MOF in rat's colon tissue. Results:The model group showed significantly increased diarrhea score,occult blood score,macroscopic damage score of colon tissue,and colon macroscopic damage index(CMDI)score,as well as elevated mRNA expression levels of HDAC3 and HDAC9,protein expression levels of HDAC3,HDAC9,and MOF,and decreased mRNA and protein expression levels of Brg1 compared to the normal group(P<0.01).In contrast,compared to the model group,the diarrhea score,occult blood score,macroscopic damage score,CMDI score,mRNA expression levels of HDAC3 and HDAC9,and protein expression levels of HDAC3,HDAC9,and MOF were significantly reduced(P<0.05 or P<0.01),while the mRNA and protein expression levels of Brg1 were significantly increased(P<0.01)in the acupuncture group,the medicinal cake-insulated moxibustion group,and the acupuncture-moxibustion group. Conclusion:Both medicinal cake-insulated moxibustion and acupuncture,either used alone or in combination,can regulate the abnormal expression of chromatin remodeling-related enzymes Brg1,HDAC3,HDAC9,and MOF in the colon tissue,thus reducing colon inflammation in CD rats.

Objective Based on TLR4/NF-κB/MLCK pathway,the therapeutic effect and mechanism of Baihe Dihuang Decoction on insomnia with intestinal flora disturbance in mice induced by p-chlorophenlalanine(PCPA)and multi-factor stimulation were studied.The aim is to provide theoretical basis for clinical use.Methods Eighty-four KM mice were randomly divided into normal group,model group,positive group(Diazepam,1.38 mg·kg-1),Baihe group(2.25 g·kg-1),Dihuang group(2.25 g·kg-1)and Baihe Dihuang Decoction group(4.5 g·kg-1).Insomnia mouse model was established by intraperitoneal injection of PCPA for 2 days combined with 4 weeks of multi-factor stimulation,including stimulating the tail with forceps clip for 2 minutes,reversing day and night for 24 hours,wetting the padding for 24 hours,tilting the cage at 45° for 24 hours,alternating the cages for 24 hours,fasting food for 24 hours,and getting cold bath for 3 minutes,etc.After successfully modeling,corresponding drug treatment was given.The anxiety-like behavior of mice was observed by elevated cross maze system.The latency and duration of sleep were observed by righting reflex experiment.16sRNA sequencing was used to analyze the composition and structure of intestinal flora in mice.The concentration changes of γ-aminobutyric acid(GABA),glutamic acid(Glu),tryptophan(Trp),5-hydroxytryptophan(5-HTP)and 5-hydroxytryptamine(5-HT)in brain and colon were detected by liquid chromatography-mass spectrometry(LC-MS).Immunohistochemical method was used to detect the expressions of zona atresia protein 1(ZO-1)and Occludin in colon.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect the genes including interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),ZO-1,Occludin,Toll-like receptor 4(TLR4),nuclear factor κB(NF-κB)and myosin light chain kinase(MLCK)in colonic tissue.Western Blot was used to detect the expressions of TLR4,NF-κB,phosphorylated nuclear factor κB(p-NF-κB),MLCK,myosin light chain(MLC)and phosphorylated myosin light chain(p-MLC)in colonic epithelial tissue.Results Compared with the normal group,the distance of entering the open arm and the duration of stay in the open arm of model group in the elevated cross maze were significantly shortened(P＜0.05).The sleep latency was significantly prolonged,and the sleep duration was significantly shortened(P＜0.05).The richness and uniformity of intestinal flora were decreased(P＜0.05,P＜0.01).The concentration of neurotransmitters GABA,Trp,5-HTP and 5-HT in the brain decreased significantly(P＜0.01),while the concentration of Glu increased significantly(P＜0.01).The concentration of GABA and Glu in colon decreased significantly(P＜0.01),while the concentration of Trp,5-HTP and 5-HT increased significantly(P＜0.01).The expression levels of inflammatory factors IL-1β,IL-6 and TNF-α in colonic tissue were significantly increased(P＜0.01),and the expression levels of ZO-1 and Occludin genes and proteins were significantly decreased(P＜0.01).The gene expression levels of TLR4,NF-κB and MLCK were significantly increased(P＜0.01),and the protein expression levels of TLR4,p-NF-κB,MLCK and p-MLC were significantly increased(P＜0.01).Compared with the model group,Baihe Dihuang Decoction could significantly prolong the distance of entering the open arm and the duration of stay in the open arm of insomnia mice in the elevated cross maze(P＜0.05).The sleep latency was significantly shortened,and the sleep duration was significantly increased(P＜0.05).The richness and uniformity of intestinal flora were increased(P＜0.05,P＜0.01).The concentration of neurotransmitters GABA,Trp,5-HTP and 5-HT in brain was increased(P＜0.05,P＜0.01),and the concentration of Glu was decreased(P＜0.01).The concentration of GABA and Glu in colon was increased(P＜0.01),while the concentration of Trp,5-HTP and 5-HT was decreased(P＜0.05,P＜0.01).The expression levels of IL-1β,IL-6 and TNF-α genes were down-regulated(P＜0.01),the expression levels of ZO-1 and Occludin genes and proteins were up-regulated(P＜0.01),TLR4,NF-κB,MLCK gene expression levels and TLR4,p-NF-κB,MLCK,p-MLC protein expression levels were down-regulated in the pathway(P＜0.01).Conclusion Baihe Dihuang Decoction can effectively treat insomnia with intestinal flora disorders.Its mechanism of action may be related to the regulation of brain and intestinal neurotransmitter disorders,down-regulating TLR4/NF-κB/MLCK signaling pathway,and up-regulating tight junction proteins expression,reducing inflammatory responses,and then repairing the mechanical barrier of intestinal mucosa.

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 study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.