1.Effectes of perfluorooctanoic acid exposure on mouse embryonic osteoblast precursor cells and its molecular mechanisms
Liming XUE ; Jiale XU ; Yuanjie LIN ; Yu'e JIN ; Dasheng LU ; Guoquan WANG
Shanghai Journal of Preventive Medicine 2025;37(7):629-635
ObjectiveTo explore the biological mechanism of bone loss caused by perfluorooctanoic acid (PFOA) through transcriptomic analysis, and to provide new insights into regulating perfluoroalkyl substances (PFAS) applications and the prevention of hazards affecting bone health. MethodsMouse embryonic osteoblast precursor cells (MC3T3-E1) were exposed to 0.1, 1, 10, and 100 μmol·L-¹ PFOA for 24 hours to assess the effects on cell viability and alkaline phosphatase (ALP) activity, and to determine the critical concentration of PFOA toxicity. The transcriptome sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) induced by PFOA. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted to identify significantly affected gene pathways. Additionally, Seahorse XF metabolic phenotyping and reverse transcription polymerase chain reaction (RT-PCR) were used to validate the key pathways. ResultsExposure to 10 and 100 μmol·L-¹ PFOA significantly reduced the cell viability and ALP activity of MC3T3-E1 cells. Therefore, the results of transcriptomic analysis for 10 μmol‧L-1 PFOA exposure found that a total of 80 DEGs were identified, including 32 upregulated genes and 48 downregulated genes. According to GO analysis, PFOA mainly affected cellular components such as mitochondrion and nucleus, molecular functions involving GTPase activity and GTP binding, as well as biological process related to mRNA processing. GSEA identified the downregulation of the β-oxidation of fatty acid pathway in mitochondria. Metabolic phenotyping reserches showed that PFOA indeed reduced mitochondrial aerobic respiration capacity and adenosine triphosphate (ATP) production, and the ratio of ATP production from cellular aerobic respiration to glycolysis was significantly decreased as well. The mRNA expression of glucose metabolism-related genes (GK, G6PD, and CS), as well as fatty acid metabolism-related genes (CPT1A and CPT2), were significantly downregulated. ConclusionPFOA reduces bone formation by inhibiting energy metabolism and β-oxidation of fatty acid pathways in osteoblasts, whihc lays the foundation for revealing the mechanism of PFOA exposure induced bone loss.
2.Abibliometric analysis of the current state of research on project management practices in hospital management
Dechao CHEN ; Yufeng SHI ; Lu YE ; Zhiming YANG ; Liming HE ; Lisha WU ; Guiyang ZHOU
Modern Hospital 2024;24(1):117-119,122
Objective To explore the research dynamics and hotspots of project management in the field of hospital man-agement,and analyze the contents that still need to be improved,so as to provide references for the subsequent research,and provide hospital managers with practical experience in hospital management.Methods Based on the PubMed database,we used the citexs data analysis platform to analyze the literature and big data from January 2012 to December 2022 on the application of project management in the field of hospital management.Results The effective literature was retrieved from 4236 articles,and the analysis found thatthe annualnumberofpublicationsinthisfield hasbeenincreasing,2021 sawthe highestannualnumberof 573 articles,and the fastest growth rate was 20.36% in 2017.The country with the most publications is the United States(1 546 articles,36.5% ),the research institution with the most publications is Monash University,Australia,the journal with the most publications is BMJ Open(124 articles),and the key words with the highest frequency of occurrence in the retrieved literature are quality improvement,primary care improvement,covid-19,telemedicine.Conclusion The research in this field has been rapidly developed and is in a fast rising phase.In almost every organization and industry,the share of project management or"projectization"is increasing,and project management has become an important part of hospital management research and prac-tice.In the context of building a modern hospital management system,the application of project management to hospital manage-ment is an effective means of improving the level of fine hospital management.
3.A bibliometric analysis of exploring the optimization path and theoretical basis of the management sys-tem of traditional Chinese medicine nursing technology in medical institutions
Xin CAO ; Yufeng SHI ; Lu YE ; Zhiming YANG ; Liming HE ; Guiyang ZHOU
Modern Hospital 2024;24(3):384-390
Objective To sort out and summarize the research hotspots and trends of Chinese medicine nursing technolo-gy at the present stage.Methods We searched the research literature on TCM nursing technology included in China Knowledge,Wanfang,and Wipu build-up to November 30,2023,and used CiteSpace 6.1.R6 software to perform co-occurrence analysis of research institutions and keyword clustering,timeline,and emergence analysis.Results A total of 5 771 documents were in-cluded,with a general upward trend in the number of publications,peaking at 692 publications in 2021.5 206 documents from 673 journals were included in the research literature,of which 19 journals had ≥50 publications(35.47%).2 087 research or-ganizations were involved,of which 27 had ≥20 publications(13.24%).Involving 9 484 authors,there were a total of 8 au-thors ≥5 in the cluster,indicating the existence of stable teamwork in the cluster.The keyword co-occurrence analysis yielded the research hotspots of TCM nursing technology as TCM nursing,training,nursing management,clinical efficacy,complica-tions,and quality of life.Conclusion Based on the econometrics and visualization analysis of the literature on TCM nursing technology,we explored the research hotspots and trends in this field,and provided two theoretical paths for medical institution managers to construct and optimize the management system of TCM nursing technology:to standardize the TCM nursing technology in hospitals and establish a clinical access management system;and based on the multidimensional management method,to inno-vate the training system of TCM nursing technology.
4.The role of virtual reality simulation training in laparoscopic skills training for young physicians
Liming SONG ; Lu WANG ; Xibin DUAN ; Chao MA ; Xuemin LI ; Ningwei YIN ; Zhongzhen WANG
Chinese Journal of Medical Education Research 2024;23(3):396-400
Objective:To explore the significance of laparoscopic virtual reality simulation training by analyzing the learning curve of laparoscopic cholecystectomy among young general surgeons who had participated in laparoscopic skills training at our hospital.Methods:Fifty young surgeons were divided into two groups, with the intervention group participating in virtual reality simulation training and the control group participating in traditional laparoscopic clinical training. After completion of the training, 30 laparoscopic cholecystectomies were performed under the supervision of highly qualified surgeons with extensive laparoscopic experience. CUSUM analysis was applied to plot the trainees' surgical learning curve based on the completion rate, surgical score and operative time. " x" is the number of surgical cases and " k" is the slope. The value of x when k=0 was calculated and the surgical learning curves and intraoperative scores of the 2 groups of trainees were compared. SPSS 23.00 was performed for t-test and Chi-square test. Results:The intervention and control groups crossed the surgical learning curve at x=19.24±0.39 and x=21.72±0.73 respectively, with significant differences ( P<0.01); the intervention and control groups scored (10.82±2.73) and (9.71±2.69) for gallbladder exposure ( t=4.61, P<0.01), (12.59±3.12) and (8.87±2.99) for gallbladder dissection triangle ( t=6.21, P<0.01), and (10.69±3.38) and (8.80±3.55) for gallbladder dissection ( t=3.10, P<0.01). Conclusions:Virtual reality simulation training can facilitate the translation of basic laparoscopic training skills into clinical skills and can promote the growth of young general surgeons.
5.Construction of Regional Integrated Platform for Pharmaceutical Care Based on the Blockchain Technology
Yu CHEN ; Qinghong LU ; Hui LUO ; Liming JIA ; Jing WANG ; Juan CAO
Chinese Journal of Modern Applied Pharmacy 2024;41(11):1543-1548
OBJECTIVE
To establish a comprehensive platform for regional pharmaceutical care among Jiangxi provincial pediatric alliance to realize the management of pediatric hierarchical diagnosis and treatment, and improve the quality of pharmaceutical care.
METHODS
A unified diagnosis and treatment information standard and a knowledge base of children's rational drug use rules were established among the medical institutions of Jiangxi provincial pediatric alliance. On this basis, the medical records and drug use information of patients in various medical institutions in the region were uploaded to the chain in a structured manner in real time, and a comprehensive platform for regional pharmaceutical care was built.
RESULTS
The comprehensive platform for regional pharmaceutical care built based on blockchain technology could share medical resources and information among medical institutions, realize rational drug use management, remote prescription review, individualized drug use guidance, popular science education, government supervision, etc., and improve the quality of pharmaceutical care.
CONCLUSION
The comprehensive platform for regional pharmaceutical care among Jiangxi provincial pediatric alliance can help allocate high-quality medical resources (drug safety knowledge base and pediatric pharmacists) for primary medical institutions. Further more, it lays the foundation for government supervision at the same time ensuring children’s medication safety, which has great practical significance.
6.Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial
Yan ZHAO ; Jianzhong ZHANG ; Bin YANG ; Jingyi LI ; Yangfeng DING ; Liming WU ; Litao ZHANG ; Jinyan WANG ; Xiaohong ZHU ; Furen ZHANG ; Xiaohua TAO ; Yumei LI ; Chunlei ZHANG ; Linfeng LI ; Jianyun LU ; Qingchun DIAO ; Qianjin LU ; Xiaoyong MAN ; Fuqiu LI ; Xiujuan XIA ; Hao CHENG ; Yingmin JIA ; Guoqing ZHAO ; Jinchun YAN ; Bo CHEN
Chinese Medical Journal 2024;137(2):200-208
Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.
7.Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer
Shi QIU ; Yaqi QIU ; Linghui DENG ; Ling NIE ; Liming GE ; Xiaonan ZHENG ; Di JIN ; Kun JIN ; Xianghong ZHOU ; Xingyang SU ; Boyu CAI ; Jiakun LI ; Xiang TU ; Lina GONG ; Liangren LIU ; Zhenhua LIU ; Yige BAO ; Jianzhong AI ; Tianhai LIN ; Lu YANG ; Qiang WEI
Chinese Medical Journal 2024;137(2):209-221
Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
8.Superior hypogastric nerve block for alleviating pain after uterine artery embolization
Yapeng SUN ; Liming SHEN ; Jian HUANG ; Yuchang LU
Chinese Journal of Interventional Imaging and Therapy 2024;21(9):532-535
Objective To explore the efficacy of superior hypogastric nerve block(SHNB)for alleviating pain after uterine artery embolization(UAE).Methods Twenty-five patients with hysteromyoma who underwent UAE were retrospectively enrolled.The patients were divided into SHNB group(n=11)and non-SHNB group(n=14,receiving peripheral intravenous analgesia)according to analgesia methods.The technique success rate and complication of SHNB were recorded.The maximum score of numeric pain-rating scale(NRS),the total dose of opioid consumption after UAE and the interval time between UAE completed to the first additional use of opioid were compared between groups.Results No significant difference of patient's age,body mass nor the maximum diameter of hysteromyoma was found between groups(all P>0.05).The technique success rate of SHNB was 100%(11/11).No complication such as lower limb radiating numbness,intravascular injection,intraperitoneal hemorrhage nor peritonitis occurred.The maximum score of NRS after UAE and the total dose of opioid consumption after UAE in SHNB group were both significantly lower,while the interval time between UAE completed to the first additional use of opioid in SHNB group was significantly longer than those in non-SHNB group(all P<0.001).Conclusion SHNB was effective for alleviating pain and reducing required dosage of analgesic medications after UAE in patients with hysteromyoma.
9.Design and clinical application of external injection sterilizing device for baby warm box
Chunqing WANG ; Liming ZHONG ; Yunxia LU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):89-91
Baby warm box belongs to one of the high-risk medical equipment of newborn life support class,the National Health Commission has formulated specific management guidelines for the daily use disinfection of baby warm box.At present,the baby warm box is generally sterilized by manual wiping of chemical disinfection liquid,which has shortcomings such as high labor intensity,low work efficiency,blind disinfection area,and chemical pollution caused by secondary residue of disinfection liquid.Ozone,as a broad spectrum high-efficiency disinfectant,has many significant advantages.Ozone disinfection has been widely used in various fields,but its inherent instability hinders transport and storage,necessitating professional devices for on-site preparation and other characteristics.These characteristics limit the use of ozone disinfection for baby warm box promotion and application.Nevertheless,some scholars have proposed the application report of bed unit ozone sterilizers and disinfection devices in the infant incubator.The study found that these two methods in practical application not only have difficult operation and control of disinfection quality but also change the original safety structure inside the infant warm box.In response,Guidong People's Hospital of Guangxi Zhuang Autonomous Region engineers designed an external injection infant incubator disinfection device and obtained the National Utility Model Patent of China(ZL 2019 2 0520907.9).The disinfection device is mainly composed of a timer,electronic ozone generator,gas supply pipeline and transfer interface,by setting the electronic ozone generator in the safe position at the bottom of the baby warm box,and then through the pipeline to the ozone generator generated by the ozone gas into the box interior to complete the disinfection process.The utilization of ozone effectively ensures the safe disinfection of the infant warm box,thereby holding significant clinical value.
10.Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous(PTEN)in sensitivity of acute myeloid leukemia to chemotherapy
LIN LIMING ; TAO JINGJING ; MENG YING ; GAN YICHAO ; HE XIN ; LI SHU ; ZHANG JIAWEI ; GAO FEIQIONG ; XIN DIJIA ; WANG LUYAO ; FAN YILI ; CHEN BOXIAO ; LU ZHIMIN ; XU YANG
Journal of Zhejiang University. Science. B 2024;25(8):700-710,中插5-中插6
Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.


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