1.Mechanism by which KRT18 interacts with mRNA and long non-coding RNA to regulate intervertebral disc nucleus pulposus cell injury
Zhongyuan LIU ; Yang LI ; Zhiwen ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(2):312-321
BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.
2.Core decompression combined with BMP activity inducing rod implantation for early femoral head necrosis
Liming ZHENG ; Feng WEN ; Wei WANG ; Zhiwen ZHANG
The Journal of Practical Medicine 2024;40(9):1280-1285
Objective To investigate the effect of core decompression combined with bone-morphogenetic proteins(BMP)activity inducing rod implantation in the treatment of early-stage femoral head necrosis.Methods Retrospective analysis of 116 patients with early-stage femoral head necrosis from June 2018 to June 2022 were divided into core decompression combined with BMP activity inducing rod group(BMP group)and allograft bone group.Sixty cases in the BMP group were treated with core decompression combined with implantation of BMP-activated induced rods,and 56 cases in the allograft group were treated with core decompression combined with bone grafting of the allograft bone by punching and compression.The differences in hip Harris scores and visual analogue scores(VAS)of pain between the two groups at preoperative,6 months postoperative and 1 year postop-erative,and the patient treatment response and femoral head survival rate at 1 year postoperative were compared.Results All patients were followed-up,and the difference between the preoperative VAS score and Harris score of the two groups was not statistically significant(P>0.05),and the VAS score and Harris score of the two groups were significantly improved at 6 months and 1 year after operation,and the BMP group was better than the allograft bone group,with significant difference(P<0.05).At 1 year after surgery,the Harris hip score excellence rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P<0.05);the femoral head survival rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P<0.05).Conclusions Core decompression combined with BMP activity induced rod implantation was effective in the treatment of early femoral head necrosis,which accelerated the induction of new bone formation,improved the quality of new bone,provided biomechanical support for the femoral head,and effectively avoided femoral head collapse.Moreover,it has good biocompatibility and couldbe degraded and absorbed in the body,which is worthy of clinical promotion.
3.Effects of electroacupuncture on MPTP-induced FoXO1/NLRP3 pathway mediated neuroinflammation in mice with Parkinson's disease
Mengni HU ; Xiaolei ZHANG ; Zhen RONG ; Yao WANG ; Ya'nan LI ; Jun MA
The Journal of Practical Medicine 2024;40(11):1494-1499
Objective To investigate whether the mechanism of action of electro-acupuncture in MPTP-induced Parkinson's disease(PD)model mice is related to neuroinflammation mediated by the forkhead box protein O1(FoXO1)/NOD-like receptor heat protein structural domain-related protein 3(NLRP3)signaling pathway.Methods Thirty mice were randomly divided into control(Ctrl),model(MPTP),and electro-acupuncture(EA)groups,with 10 mice in each group.PD mouse model was prepared by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)30 mg/(kg·d)for 7 d consecutively.Behavioral changes of mice were observed by open field and pole-climbing experiments;α-synuclein(α-syn)expression in the substantia nigra of the midbrain was observed by immunohistochemistry;FoXO1,NLRP3,ASC,and Caspase-1 were deter-mined by Western blot;and the expression of inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)was detected by ELISA in the substantia nigra of the midbrain.Results Mice in the MPTP group showed significant behavioral deficits,with a significant increase in midbrain substantia nigra α-syn(P<0.01),elevated levels of Iba-1,FoXO1,NLRP3,ASC,and Caspase-1 proteins(P<0.05 and P<0.01,respectively),and a significant increase in the levels of TNF-α,and IL-1β(P<0.01).The treatment of EA was effective in improve the dyskinesia of PD mice,improve motor balance and coordination(P<0.01),reduce the abnormal aggregation of α-syn(P<0.01),reduce the abnormal activation of microglia,and alleviate neuroinflammation(P<0.05).Conclusion Electro-acupuncture may play a protective role in PD by modulating FoXO1/NLRP3 pathway-mediated neuroinflammation.
4.Comparative Study on Intelligent Audit and Monitoring Repository of Focused Audit Violations under DRG Payment
Zhiguo ZHANG ; Qingqin LIU ; Chen XIANG ; Xiangping LIU
Chinese Hospital Management 2024;44(6):77-82
Objective Comparative analysis of rule categories,key audit behaviors,and the degree of correspon-dence between rules and behaviors through intelligent auditing of key audit violations and monitoring of the rule base.To provide reference for the improvement of intelligent audit and monitoring rule library for key audit violations under DRG payment in medical insurance fund.Methods Searching and collecting policy documents such as DRG payment management methods issued by local health insurance bureaus from May 20,2019 to December 31,2023 and the literature related to DRG payment smart audit monitoring rules in the database,and targeting the rules therein that are related to the focus on auditing irregularities under the DRG payment.Literature analysis and comparative analysis were used to summarize and analyze the rules related to key audit violations under DRG payment.Results The intelli-gent audit rules for key audit violations under DRG payment can be divided into two major categories:logical judg-ment and parameter index,and the degree of correspondence between audit rules and key audit behaviors varies.Conclusion(1)Unify the key audit rules nationwide to ensure the universality and comprehensiveness of the rules;(2)Deepen the current situation of regional illegal activities and strengthen local characteristics;(3)Improve the quality of logical judgment rules and increase the quantity of parameter indicator rules;(4)Strengthen scientific re-search on new types of violations,and establish more targeted regulatory rules.
5.A Study of Organisational Support Strategies to Promote Mental Health among Healthcare Workers
Luo XU ; Yinhuan HU ; Xiandong FENG
Chinese Hospital Management 2024;44(9):53-57
Objective To sort out the organisational support strategies adopted by typical public hospitals to improve the mental health of healthcare workers,to provide reference for hospitals around the world,and to enhance the healthcare health force.Methods In December 2023,57 cases of organisational support for healthcare workers'mental health in public hospitals were searched and screened,and the textual content of specific measures in the case hospitals was coded using thematic framework analysis.Two rounds of expert consultation were conducted to further screen typical cases.Results 4 General strategies of system optimisation,professional services,promotion and education,and humanistic care and their corresponding 9 sub-strategies were identified based on the coding content.The 11 typical cases screened by experts were further summarised and analysed to distil the specific practices carried out by each hospital to improve the mental health of healthcare workers.Conclusion The mental health status of healthcare workers is not optimistic,and hospitals need to pay full attention to it and take supportive organisational measures to address the existing problems.For example,expanding the reserve of psychological professionals,enhancing the application of information technology,and improving the willingness of healthcare professionals to accept mental services.
6.Study on the Mechanisms of Successful Aging at Work of Senior Clinicians in Public Hospitals Based on Grounded Theory
Yating CONG ; Min WANG ; Jingjia ZHU ; Yueming LI ; Hongbing TAO
Chinese Hospital Management 2024;44(11):65-69
Objective An exploratory study of the mechanisms for achieving successful aging at work of clinicians in public hospitals by applying grounded theory and proposing appropriate management recommendations.Methods 24 medical staff from 5 public hospitals in Hubei and Shandong Provinces were interviewed in semi-structured interviews by using purposive sampling methods from June to August in 2023.The interview records were coded,analyzed and integrated with grounded theory.Results Through open coding,spindle coding and selective coding,204 original concepts,47 categories,16 main categories and 5 core category related to model of the mechanism for achieving successful aging at work of clinicians.Conclusion Successful aging at work of senior clinicians encompasses five main areas:physical and mental health,work adaptation,relationships and legacy,internal and external compensation,and value realization.Organizational support factors,individual job crafting affect successful aging at work of senior clinicians by meeting the psychological needs,achieving effective resource management,and promoting person-job matching;individual characteristic factors play a moderating role;job crafting mediates the effect of organizational support factors on successful aging at work among clinicians.
7.Effect of electroacupuncture on the NEK7/NLRP3 inflammatory signaling pathway in intestine of mice with Parkinson's disease
Hanzhang LI ; Yanan LI ; Lei GUO ; Yao WANG ; Xiaolei ZHANG ; Mengni HU ; Ling QI ; Zhen RONG ; Jun MA
Journal of Beijing University of Traditional Chinese Medicine 2024;47(10):1466-1473
Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P<0.01);the average optical densities of nigral TH and colon occludin were decreased(P<0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P<0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P<0.01);the average optical densities of nigral TH and colon occludin were increased(P<0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P<0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.
8.Exploring the mechanism of pre-electroacupuncture at"Neiguan"(PC6)and"Jianshi"(PC5)acupoints on learning,memory,and locus coeruleus-hippocampal neural circuit in Alzheimer's disease-like rats via the β2AR/β-arrestin2/NF-κB pathway
Chuan HE ; Li WANG ; Xiaoli PAN ; Chaochao YU ; Juan XIAO ; Zhenkun LU ; Xiangyu LI ; Yanjun DU ; Feng SHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1612-1622
Objective To investigate the effects of pre-electroacupuncture(EA)on spatial learning and memory,the locus coeruleus-hippocampal neural circuit,and neuroinflammation in Alzheimer's disease(AD)-like rats,and to explore the possible mechanism of pre-EA in preventing and treating AD.Methods Thirty-six male SD rats were divided into the normal,model,EA,and sham EA groups using the random number table method,with nine rats per group.An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d)D-galactose for eight consecutive weeks.After daily intraperitoneal injection,the rats in the EA group underwent EA stimulation at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints with a continuous wave,frequency of 50 Hz,and a current of 1 mA for 20 min once a day for 8 weeks.The sham EA group was only superficially punctured to the subcutaneous tissue at the"Neiguan"(PC6)and"Jianshi"(PC5)acupoints without electricity,and the rest of the operations were the same as those in the EA group.The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats.Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons,as well as glial fibrillary acidic protein and tumor necrosis factor-α(TNF-α)co-localization in the CA1 area of the hippocampus of astrocytes.Western blotting was used to measure the protein expressions of norepinephrine(NE),β2-adrenergic receptor(β2AR),β-inhibitory protein 2(β-arrestin2),nuclear transcription factor-κB(NF-κB)inhibitory factor protein α(IκBα),and NF-κB in the hippocampus of rats.An enzyme-linked immunosorbent assay was used to detect the TNF-α,interleukin-1β(IL-1β),and interleukin-6(IL-6)contents in hippocampal tissue.Results Compared with the normal group,the average escape latency of the model group rats was prolonged,and the times of crossing platform and exploration time in the target quadrant were reduced(P<0.01),while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant(P<0.01).Compared with the normal group,the expression of co-located noradrenergic neurons in the model group decreased,co-located astrocytes increased(P<0.01);NE,β2AR,β-arrestin2,and IκBα protein expression decreased(P<0.01),NF-κB protein expression increased(P<0.01);the contents of TNF-α,IL-1β,and IL-6 increased(P<0.01).Compared with the model group,the EA group showed an increase in the expression of co-located noradrenergic neurons,a decrease in co-located astrocytes(P<0.01),an increase in NE,β2AR,β-arrestin2,and IκBα protein expressions(P<0.01),a decrease in NF-κB protein expression(P<0.01),and a decrease in TNF-α,IL-1β,and IL-6 levels(P<0.01).No significant difference was observed in the above indicators between the model and sham EA groups.Conclusion Pre-EA at"Neiguan"(PC6)and"Jianshi"(PC5)can alleviate learning and memory dysfunction,alleviate noradrenergic neuronal loss in the locus coeruleus,inhibit astrocyte activation,protect the locus coeruleus-hippocampal neural circuit,and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.
9.Exploration on the Connotation,Characteristics and Path of High-quality Development of Health Care
Chinese Health Economics 2024;43(6):18-22,35
Promoting high-quality development of health care is a strategic choice for realizing Chinese-style health care modernization at a higher level in the new era.At present,promoting the high-quality development of health care is a brand new theoretical and practical issue.Based on defining the boundaries of health care,it explores the connotation and characteristics of the high-quality development of health care:guided by the new development concept and centered on residents'health,it aims to meet residents'diversified and high-standard health needs,focusing on quality and efficiency enhancement,and ultimately achieving a higher level of health for the population,as well as the promotion and maintenance of health.In the process of development,attention needs to be paid to the public welfare of medical and health services,the equity and accessibility of health services,the synergy of health subjects,the practice of residents'health behaviors,and the hierarchy of development stages.To achieve high-quality development of China's health care in the new era,it is necessary to promote the matching of policy supply and demand and improve the quality of the factors of production of health care;to gather strong human resources to support the innovative allocation of the factors of production of health care;to give rise to diversified innovation bodies and promote the optimal combination of the factors of labor in health care;and to cultivate a health ecosystem and create a long-term endogenous impetus for the health of the entire population.
10.Clinical Observation of Supplemented Wendan Decoction Combined with Western Medicine in Treatment of Insomnia Accompanied by Anxiety and Depression in Phlegm-heat Internal Disturbance Syndrome
Jinzhen JIANG ; Guohua CHEN ; Xinhua SONG ; Yihan ZHANG ; Zhiyu LUO ; Guang WANG ; Junhua MEI
Herald of Medicine 2024;43(2):221-227
Objective To explore the clinical effect of clinical observation of supplemented wendan decoction combined with Western medicine in treating insomnia accompanied by anxiety and depression in phlegm-heat internal disturbance syndrome.Methods A total of 120 cases of insomnia with anxiety and depression comorbiditis with phlegm heat disturbance syndrome were randomly divided into control group and treatment group,60 cases in each group.The control group was given escitalopram oxalate tablet combined with dexzopiclonone tablet,and the observation group was given added Wendan decoction on the basis of the control group.Both groups were treated continuously for 6 weeks.Polysomnography monitoring parameters and heart rate variability were compared between the two groups during baseline period and visit 2(baseline period+3 months).Scale scores of the two groups were compared during baseline period,visit 1(baseline period+6 weeks)and visit 2.The content of heart rate variability includes:time domain analysis(standard deviation of normal interval(SDNN),square root of the square sum of the mean of the difference between adjacent normal interval(RMSSD)and frequency domain analysis(LF,HF,LF/HF).The scale scores included the Pittsburgh Sleep Quality Index(PSQI)and Insomnia Severity Index(ISI)to assess sleep status,and the Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Self-assessment Scale for Depression(PHQ-9)and Generalized Anxiety Disorder Scale(GAD-7)to assess anxiety and depression status.Results(1)Polysomnography monitoring:the wake time of observation group was significantly shorter than that of control group,the number of awakenings was significantly less than that of control group,and the percentage of N3 and REM was significantly higher than these of control group(P<0.05).(2)Heart rate variability:RMSSD and HF values in the observation group were significantly higher than those in the control group,and LF/HF values were significantly lower than those in the control group(P<0.05).(3)In terms of sleep:during the interview,PSQI total score,sleep quality,hypnotic drugs and daytime dysfunction in the observation group were significantly lower than those in the control group(P<0.05);At the 3 months,the sleep quality,hypnotic drugs and daytime dysfunction in the observation group were significantly lower than those in the control group(P<0.05).In terms of emotion:HAMA,HAMD and GAD-7 scores were significantly lower than those of control group at 6 weeks(P<0.05);At the 3 months,HAMA and GAD-7 scores were significantly lower than those of control group(P<0.05).Conclusion Supplemented Wendan decoction combined with western medicine can obviously optimize the sleep structure of insomnia patients with anxiety and depressionof phlegm-heat disturbance syndrome,improve sleep continuity and deepen sleep depth,and improve parasympathetic functional activities,contribute to sympathetic parasympathetic balance,can improve insomniaand depression symptoms recently,and significantly improve anxiety symptoms in the short term,with good safety.

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