1.Protective effect of Shenfu injection against neonatal hypoxic-ischemic brain injury by inhibiting the ferroptosis
Xiaotong Zhang ; Meng Zhang ; Gang Li ; Yang Hu ; Yajing Xun ; Hui Ding ; Donglin Shen ; Ming Wu
Acta Universitatis Medicinalis Anhui 2025;60(1):31-40
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.
2.Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement.
Yiyao CHEN ; Bingxin YANG ; Xiaoyu Merlin ZHANG ; Songchang CHEN ; Minhui WANG ; Liya HU ; Nina PAN ; Shuyuan LI ; Weihui SHI ; Zhenhua YANG ; Li WANG ; Yajing TAN ; Jian WANG ; Yanlin WANG ; Qinghe XING ; Zhonghua MA ; Jinsong LI ; He-Feng HUANG ; Jinglan ZHANG ; Chenming XU
Protein & Cell 2024;15(1):52-68
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
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Animals
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Mice
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Humans
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Child, Preschool
;
Intellectual Disability/genetics*
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Heart Defects, Congenital/genetics*
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Facies
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Cleft Palate
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Muscle Hypotonia
3.Low-frequency electrical stimulation relieves pain and promotes gastrointestinal function recovery after gynecological laparotomy
Yajing YANG ; Weipei ZHU ; Liulin ZHOU
Basic & Clinical Medicine 2024;44(2):252-255
Objective To observe the effect of low-frequency electrical stimulation on the rehabilitation of pa-tients after gynecological abdominal surgery.Methods Sixty-three patients who underwent open surgery in gy-necology department of Taixing Clinical College of Bengbu Medical College from June 2021 to July 2022 were selected.The patients were randomly divided into control group(31 cases)and a low-frequency electrical stimulation group(32 cases).The low-frequency electrical stimulation group was subjected to stimulation with-in the patient′s tolerable range once a day for 30 minutes each time,and the intensity of each stimulation was adjusted based on clinical situation.The control group selected the same acupoints and pasted electrodes,connected to the treatment device but no electrical stimulation.The electrode strip was removed after 30 minutes,then re-cord the postoperative Visual Analog Scale(VAS)score as well as the time from the end of the surgery to the first discharge and defecation.Results The VAS score at 48 hours after surgery showed a low degree of pain in the low-frequency electrical stimulation group(3.6±1.2)compared to that in control group(4.5±1.4);After 72 hours of surgery,the VAS score was lower in the low-frequency electrical stimulation group(1.7±0.9)compared to the control group(3.3±1.4),indicating a lower degree of pain.The first exhaust time(26.9±6.7)h vs.(35.5±13.0)h was shorter in the low-frequency electrical stimulation group;The first bowel movement time(49.0±5.4)h vs.(64.4±13.8)h was shorter in the low-frequency electrical stimula-tion group compared to the control group.Conclusions Low frequency electro-physiological stimulation can alleviate post-operative pain and shorten exhaust and defecation time in patients undergoing gynecological open surgery.
4.Mechanism of the immediate analgesic effect of the"three methods and three points"tuina technique based on the IL-17F/IL-17RC signaling pathway and M1 microglia
Jinping CHEN ; Zhifeng LIU ; Tianyuan YU ; Hourong WANG ; Yingqi ZHANG ; Qian GUAN ; Yajing XU ; Zhenjie YANG ; Chula SA ; Runlong ZHANG ; Hanyu ZHANG ; Jiayue LIU ; Jiawei SUN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(1):116-123
Objective By observing the effects of"three methods and three points"tuina technique on the expression of interleukin-17F(IL-17F),interleukin-17 receptor C(IL-17RC),activator 1 of nuclear transcription factor-κB(Act1),tumour necrosis factor receptor-associated factor 6(TRAF6)and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI)model,we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP).Methods Thirty-six SD rats were divided into the sham group,the model group and the tuina group according to the random number method,twelve rats in each group,and the minor CCI model was replicated by ligating the right sciatic nerve.The rats in the tuina group were subjected to pointing,plucking and kneading at the BL37,BL57 and GB34 points on the affected side using a tuina simulator,while the sham group and the model group were only grasped and restrained,and were intervened for one time.The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention.The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting.The mRNA expression of IL-17F,IL-17RC,Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR.The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence.Results Behavioral results showed that before intervention,compared with the sham group,paw mechanical withdraw threshold(PMWT)decreased and cold sensitivity threshold(CST)increased in the model group and the tuina group;after tuina intervention,PMWT in the tuina group was increased,and CST was decreased compared with the model group;after intervention,PMWT in the tuina group was increased,while CST was decreased(P<0.05).RT-PCR results showed that compared with the sham group,mRNA expression levels of IL-17F,IL-17RC,TRAF6 and Act1 in the spinal dorsal horn of the model group were increased;compared with model group,the mRNA expression levels of above indexes in the tuina group were decreased(P<0.05).Western boltting results showed that compared with the sham group,the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased;compared with the model group,the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P<O.05).Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group;compared with the model group,the mean fluorescence intensity of CD40 in the tuina group was decreased(P<0.05).Conclusion The"three methods and three points"tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F,IL-17RC,Act1,TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention.
5.Longitudinal extrauterine growth restriction in extremely preterm infants: current status and prediction model
Xiaofang HUANG ; Qi FENG ; Shuaijun LI ; Xiuying TIAN ; Yong JI ; Ying ZHOU ; Bo TIAN ; Yuemei LI ; Wei GUO ; Shufen ZHAI ; Haiying HE ; Xia LIU ; Rongxiu ZHENG ; Shasha FAN ; Li MA ; Hongyun WANG ; Xiaoying WANG ; Shanyamei HUANG ; Jinyu LI ; Hua XIE ; Xiaoxiang LI ; Pingping ZHANG ; Hua MEI ; Yanju HU ; Ming YANG ; Lu CHEN ; Yajing LI ; Xiaohong GU ; Shengshun QUE ; Xiaoxian YAN ; Haijuan WANG ; Lixia SUN ; Liang ZHANG ; Jiuye GUO
Chinese Journal of Neonatology 2024;39(3):136-144
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.
6.Reliability and validity of assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Peri-operative Period
Boyang YU ; Yanyan YANG ; Ao MA ; Tao LI ; Xiaoxie LIU ; Zhengyang LI ; Yajing DUAN ; Jiaqi LIU ; Yuxiao XIE ; Cui WANG ; Zhen HUANG ; Lining ZHANG ; Xinyi LIU ; Zishan JIA ; Mouwang ZHOU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(9):1053-1059
Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.
7.Study on the management strategy of anticancer drugs in pharmacy intravenous admixture services based on failure mode and effect analysis
Dianli YANG ; Jing LI ; Yajing YU
China Pharmacist 2024;27(5):841-847
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.
8.Establishment and methodological validation of a nucleic acid detection method for human parvovirus B19
Yue WANG ; Xiaobei ZHENG ; Yajing ZHENG ; Yu SUN ; Qin GONG ; Linlin ZHANG ; Ying ZHAO ; Dandan YANG ; Yi YANG ; Lin LI ; Boran LI ; Jin ZHANG
Chinese Journal of Blood Transfusion 2024;37(11):1234-1240
[Objective] To establish a real-time fluorescence quantitative PCR nucleic acid detection method of human parvovirus B19 and validate the method systematically. [Methods] Specific primers and probes for the highly conserved regions of the three genotypes of B19 virus were designed, and B19 quantitative amplification standard curves were established. The accuracy, precision (repeatability and intermediate precision), linear range, quantification limit, detection limit, specificity, anti cross contamination, genotyping and anti-interference ability of this method were verified. [Results] When the quantitative reference range for B19 virus was 2.0×101 to 1.0×108 IU/mL, a double logarithmic regression analysis was performed between the measured values and the theoretical values, and the regression equation R2≥0.98 showed good linear correlation. The quantification limit was 20 IU/mL, with a detection rate of 100%. The detection limit was 10 IU/mL, and the detection rate is 95.23%. Three genotypes of B19 virus samples can be effectively detected. The plasma of seven non B19 pathogens, including hepatitis A virus, hepatitis B virus, hepatitis C virus, human immuno-deficiency virus, human cytomegalovirus, hepatitis E virus and Treponema pallidum, was non reactive and has good species specificity. Simultaneously, in the presence of seven other concurrent pathogens, positive samples with a weak positive concentration of E3 IU/mL could be stably detected, and the B19 nucleic acid testing method was not interfered with. When the hemoglobin concentration was 431 mg/dL, triglycerides (1 269 turbidity) and unconjugated bilirubin concentration was 20 mg/dL, this method was non reactive for all three common plasma interfering substances. In the presence of three common plasma interfering substances, positive samples with a weak positive concentration of E3 IU/mL could be stably detected, and the B19 nucleic acid testing method was not interfered with. The deviation between the detection values of standard substances at two concentration levels of S1 (E5 IU/mL) and S2 (E4 IU/mL) and the target values were≤±0.5 log value. The CV values of positive sample 1 (concentration level E5 IU/mL) and positive sample 2 (concentration level E4 IU/mL) for daily precision confirmation and continuous 5-day intra-day precision confirmation were both≤5%. [Conclusion] This method has strong specificity, high sensitivity, wide linear range, stability, reliability and high accuracy, and can be used for the detection of human parvovirus B19 nucleic acid in plasma.
9.Application and development of multi-modal data fusion technology in nursing decision support system
Wenqing CAI ; Chen ZHANG ; Yuyang ZHANG ; Yajing SU ; Wanjun CHEN ; Yang CHEN ; Yumeng ZHANG ; Qingyin LI
Chinese Journal of Modern Nursing 2024;30(28):3805-3809
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.
10.a case of paraneoplastic cerebellar ataxia syndrome associated with immunocheckpoint inhibitor treated with Ofatumumab
Yajing LIU ; Shuanghao FENG ; Jiajia JIANG ; Yi YANG ; Hui BU
Chinese Journal of Nervous and Mental Diseases 2024;50(3):159-161
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.


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