1.Research on the establishment of capability evaluation system and training and exercise models of the national emergency medical rescue team
Dan ZHOU ; Jian YIN ; Caiping GAO ; Lingyu LI ; Liming ZHAO ; Zhongmin LIU
Shanghai Journal of Preventive Medicine 2024;36(3):262-268
ObjectiveTo improve the response capabilities to disasters and prevent major epidemics, it is of practical use to study the capability evaluation system of the national emergency medical rescue team that combines theoretical training and practical exercises, to enhance the overall quality of the teams. MethodsFirst, a capability assessment system for the national emergency medical rescue team was constructed based on the INSARAG External Classification (IEC) standards of the national emergency medical rescue team. Then, based on the outcome based education (OBE) concept, we conducted innovative research on the curriculum design and exercise programs for team building and member training. Finally, an empirical analysis was conducted on the effectiveness of the evaluation system and training exercises based on the statistical analysis of the comprehensive quality evaluation of the Shanghai national emergency medical rescue team from 2020 to 2023, as well as the empirical analysis of the rescue exercise on the Cruise of spectrum. ResultsBased on the linear regression analysis of each core competency indicators, the five core competencies in the evaluation system, including rescue skills, medical and health knowledge, disaster coping ability, team cooperation ability, and mental resilience training, were positively correlated with the cumulative number of trainings (r=0.71, r=0.76, r=0.81, r=0.84, r=0.96,all P<0.05), indicating that the training was effective and the course design was reasonable. Empirical cases showed that the three-dimensional rescue drill model had remarkable results in the actual combat application and ability improvement of team members. ConclusionThe training courses and drills designed based on the three-level assessment system are effective in improving the comprehensive capabilities of the national emergency medical rescue team.
2.Inhibitory effect of berberine on migration and invasion of human glioma T98G cells and its mechanism
Yuxue SUN ; Ziqiang LIU ; Hao WU ; Liming ZHAO ; Tao GAO ; Haiyan HUANG ; Chaoyue LI
Journal of Jilin University(Medicine Edition) 2024;50(1):50-57
Objective:To discuss the regulatory effect of berberine(BBR)on fatty acids in the human glioma T98G cells and its effect on the cell proliferation,migration,and invasion,and to clarify its potential mechanism.Methods:The T98G cells at logarithmic growth phase were divided into control group and different concentrations(25,50,and 100 mg·L-1)of BBR groups.Cell wound healing assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the invasion rates of the cells in various groups.The T98G cells at logarithmic growth phase were divided into control group and 100 mg·L-1 BBR group,and Mass spectrometry was used to detect the fatty acid contents in the cells in two groups.The T98G cells at logarithmic growth phase were divided into control group and different concentrations(50,100,and 150 mg·L-1)of BBR groups;Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(AKT),phosphorylated AKT(p-AKT),sterol regulatory element-binding protein 1(SREBP-1),and fatty acid synthase(FASN)in the cells in various groups.The expression of FASN was suppressed by gene silencing technology,and the T98G cells at logarithmic growth phase were divided into control group,shFASN1 group,and shFASN2 group.Western blotting method was used to detect the expression levels of FASN protein in the cells in various groups;clone formation assay was used to detect the clone formation of the cells in various groups;cell wound healing assay was used to detect the migration rates of the cells in various groups.Results:Compared with control group,the migration rates and invasion rates of the cells in different concentrations of BBR groups were decreased in a concentration-dependent manner(P<0.01),and the fatty acid content in the cells in 100 mg·L-1 BBR group was significantly decreased(P<0.01).Compared with control group,the expression levels of p-PI3K,p-AKT,SREBP-1,and FASN proteins in the cells in 150 mg·L-1 BBR group were significantly decreased(P<0.05 or P<0.01),and the expression level of SREBP-1 protein in the cells in 100 and 150 mg·L-1 BBR groups were significantly decreased(P<0.01).After suppression of FASN expression,compared with control group,the expression levels of FASN protein in the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the expression level of FASN protein in the cells in shFASN2 group was lower than that in shFASN1 group(P<0.05);compared with control group,the numbers of clone formation and migration rates of the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the migration rate of the cells in shFASN2 group was significantly lower than that in shFASN1 group(P<0.05).Conclusion:BBR interferes with fatty acid synthesis in the glioma T98G cells by reducing the expression of the PI3K/AKT/SREBP-1/FASN pathway related proteins,and decrease their migration and invasion capabilities.
3.Advances in the application of artificial intelligence in nucleic acid drug development
Zi'ang HU ; Liming GAO ; Wenying YU
Journal of China Pharmaceutical University 2024;55(3):335-346
In recent years,the field of nucleic acid therapeutics has been flourishing,progressively establishing itself as the third generation of drug modalities following small molecules and antibody-based drugs.Artificial intelligence technology based on machine learning is advancing rapidly,which can significantly accelerate the development process of nucleic acid therapeutics.This review provides an overview of the foundational aspects of artificial intelligence algorithms,databases,and characterizations in the field of nucleic acid drug development.It elucidates the advances in the application of artificial intelligence in nucleic acid structural prediction,small nucleic acid drug design,and other research and development phases of nucleic acid therapeutics,aiming to offer some reference for the interdisciplinary development of artificial intelligence and nucleic acid drugs.
4.Phacoemulsification with intraocular lens implantation plus goniosynechialysis and goniotomy under intraoperative gonioscope for the treatment of advanced primary angle-closure glaucoma with cataract
Sijia GAO ; Yu WEN ; Qianqian WAN ; Heting LIU ; Liming TAO
International Eye Science 2024;24(6):864-869
AIM: To evaluate the efficacy of phacoemulsification with intraocular lens implantation(PEI)combined with goniosynechialysis(GSL)and goniotomy(GT)under direct vision with gonioscope in the treatment of advanced primary angle-closure glaucoma(PACG)combined with cataract.METHODS: Retrospective case series study. A total of 62 patients(65 eyes)with advanced PACG combined with cataract who were treated in the Second Hospital of Anhui Medical University from December 1, 2021 to March 31, 2023 were enrolled, and they were divided into two groups according to different surgical methods. The control group(32 cases, 33 eyes)received PEI+GSL, whereas the observation group(30 cases, 32 eyes)received PEI+GSL+GT. The intraocular pressure(IOP), best corrected visual acuity(BCVA)and the number of anti-glaucoma medications of the two groups before surgery and at 1 d, 1 wk, 1, 3, and 6 mo after surgery were evaluated. In addition, the visual field, cup-to-disc ratio(C/D), angle open range, anterior chamber depth, and average thickness of retinal nerve fiber layer(RNFL)were evaluated before and 6 mo after surgery.RESULTS: There were significant differences in IOP and lowering range of average IOP at 6 mo between the PEI+GSL+GT group(16.68±2.65, 11.12±8.53 mmHg)and the PEI+GSL group(18.71±2.51, 8.32±4.17 mmHg; P<0.05), and there was no difference in the rate of IOP reduction(44.57%±21.79% and 35.20%±17.94%, P>0.05). The number of anti-glaucoma medications, BCVA, anterior chamber depth, and angle closure range were improved in the two groups at 6 mo after operation(all P<0.01). The number of medication reductions and the range of angle opening at 6 mo after surgery in the PEI+GSL+GT group were significantly higher than those in the PEI+GSL group(P<0.05), and there was no difference in the other indicators between the two groups(all P>0.05). There was no difference in the mean deviation of visual field, C/D and average thickness of RNFL between the two groups at 6 mo after operation compared with those before operation(all P>0.05). The complete surgery success rate of the PEI+GSL+GT group was 81%(26/32), and the conditional success rate was 94%(30/32); while those rates of the PEI+GSL group were 58%(19/33)and 76%(25/33), respectively. There were statistical significance in the success rate of surgery between the two groups(complete success rate χ2=4.275, P=0.039; conditional success rate χ2=4.040, P=0.044). No vision-threatening complications and another surgery occurred in either group.CONCLUSION: The study showed that for patients with advanced PACG with cataract, PEI+GSL+GT is more effective than PEI+GSL.
5.Clinical and CT radiomics features for predicting microsatellite instability-high status of gastric cancer
Pengchao ZHAN ; Liming LI ; Dongbo LYU ; Chenglong LUO ; Zhiwei HU ; Pan LIANG ; Jianbo GAO
Chinese Journal of Medical Imaging Technology 2024;40(1):77-82
Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P<0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P<0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.
6.An integrated curriculum for epidemiology and medical statistics teaching in undergraduate students majoring in clinical medicine: lesson learned from teaching reform
Yuanjie PANG ; Xue CONG ; Chunxiao LIAO ; Wenjing GAO ; Canqing YU ; Jun LYU ; Tao WU ; Siyan ZHAN ; Liming LI
Chinese Journal of Epidemiology 2024;45(11):1598-1604
Epidemiology and medical statistics are essential courses for undergraduate students majoring in clinical medicine. By studying the two courses, they can obtain the core skills for their future clinical practice. High-level medical schools both at home and abroad have accumulated successful experiences in curriculum, teaching methods and teaching models of the two disciplines. These colleges have also carried out the exploration of the curriculum reform centering on "organ systems integration". This paper summarizes the current status of epidemiology and medical statistics teaching and curriculum integration in representative medical schools both at home and abroad, and puts forward suggestions for deepening teaching reform and optimizing the curriculum system to provide reference for the integration of epidemiology and medical statistics curriculums for undergraduate students majoring in clinical medicine in China.
7.Efficacy of different concentrations of ZKY001 eyedrops in the treatment of corneal epithelial defect after primary pterygium excision
Hua GAO ; Lei ZHU ; Jianjiang XU ; Liming TAO ; Yanling DONG ; Luxia CHEN ; Xiuming JIN ; Guigang LI ; Huping WU ; Ping ZHAO ; Wei CHEN ; Xiaoyi LI ; Weiyun SHI
International Eye Science 2024;24(12):1888-1894
AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.
8.Research on the regulation of ferroptosis in hepatic stellate cells line LX2 by recombinant cytoglobin
Xun-wei DUAN ; Gui-qing XIAO ; Huai-yu CHEN ; Yong ZHANG ; Wen-lin WU ; Yi GAO ; Yong DIAO
Acta Pharmaceutica Sinica 2024;59(8):2237-2244
Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin
9.Pan-cancer analysis of the role of SDHB gene in patients with pheochromocytoma and paraganglioma
Pu WANG ; Liming GAO ; Wenyang ZHANG ; Yin XIA
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(11):692-697
OBJECTIVE To investigate the expression and prognosis of SDHB gene in pan-cancer by bioinformatics analysis,and to explore SDHB-related genes,potential pathways and immune cell infiltration in pheochromocytoma paraganglioma(PPGL).METHODS The expression of SDHB gene in pan-cancer and its relationship with survival prognosis were analyzed in The Cancer Genome Atlas(TCGA)and genotype-tissue expression(GTEx)databases.The expression changes of other genes affected by SDHB mutations,the enrichment analysis and signaling pathway analysis in PPGL patients were carried out by analyzing the TCGA database and the TARGET database.In addition,the relationship between SDHB expression and immune cell infiltration in PPGL patients was explored.RESULTS Compared with normal tissues,the expression of SDHB in 21 tumors was higher than that in normal tissues(P<0.01):BLCA,BRCA,CESC,COAD,DLBC,ESCA,GBM,HNSCC,LGG,LUAD,LUSC,OV,PAAD,PRAD,READ,SKCM,STAD,THCA,THYM,UCEC and UCS.It was expressed lower than normal in 7 other tumors(P<0.01),including ACC,CHOL,KICH,KIRC,KIRP,LAML and PPGL.The relationship between SDHB expression and survival prognosis was analyzed,and it was found that in STAD,KIRC,MESO,OS,and KIR,lower SDHB expression predicted poor prognosis,while higher expression predicted good prognosis.In UCEC,LGG,HNSCC,LAML,OSCC,and ACC,lower SDHB expression predicted a better prognosis,and similarly,higher expression predicted a poor prognosis.In correlation and enrichment analysis,the expression of SDHB was mainly related to neuroactive ligand-receptor interaction,Cushing's syndrome,cortisol synthesis and secretion,peptide receptor activity,G protein-coupled peptide receptor activity,neuropeptide receptor activity,intrinsic components of the synaptic membrane,components of the synaptic membrane,components of the postsynaptic specialized membrane,cyclic nucleotide-mediated signaling pathways,neuropeptide signaling pathways,glucocorticoid metabolism processes and other signaling pathways.In immune infiltration analysis,it was found that the immune cells with the highest infiltration in the SDHB lower expression group were pDC cells and TReg cells,suggesting that pDC cells and TReg cells may play a certain role in PPGL patients.CONCLUSION SDHB gene is abnormally expressed in a variety of tumors,and it has a certain correlation with the prognosis of tumors.In PPGL patients,the signaling pathways affected by SDHB and highly infiltrating immune cells provide new insights for future mechanistic studies and immunotherapy.
10.Efficacy and prognostic survival analysis of pembrolizumab combined with apatinib and chemotherapy in treating human epidermal growth factor receptor-2-negative advanced gastric cancer
Hongmei XU ; Tao ZHOU ; Lanlan CHEN ; Lifang GUAN ; Liming GAO ; Chaoqun WANG
Clinical Medicine of China 2024;40(6):408-414
Objective:To investigate the efficacy and prognostic survival of pembrolizumab combined with apatinib and chemotherapy in the treatment of human epidermal growth factor receptor-2 (HER2)-negative advanced gastric cancer.Methods:Patients with HER2-negative advanced gastric cancer were selected from December 2019 to December 2022 as the study subjects. Forty-five patients who received chemotherapy therapy (fluorouracil+cisplatin) were randomly collected and included in control group, and 52 patients who were treated with pembrolizumab combined with apatinib were randomly selected and enrolled as observation group. The difference in short-term efficacy was compared. The levels of serum tumor markers and immune function (CD3 +, CD4 +, CD8 +, CD4 +/CD8 +) were recorded. The long-term efficacy and adverse reactions of patients were compared. Measurement data conforming to the normal distribution were expressed as xˉ± s, and the mean comparison between groups was performed by independent sample t test. Chi-square test was used to compare the rate or composition ratio among enumeration data. P<0.05 was considered statistically significant. Results:At 6 months after treatment, the disease control rate in observation group was significantly higher than that in control group (78.85% (41/52) vs 57.78% (26/45)) ( χ2=5.01, P=0.025), but there was no statistical significance in objective response rate between groups (36.54% (19/52) vs 24.45% (11/45)) ( χ2=1.65, P=0.199). The levels of pepsinogen I, tissue polypeptide specific antigen, carcinoembryonic antigen, carbohydrate antigen 199 and CD8 + in both groups were reduced after treatment, and the levels were lower in observation group than those in control group ( t=6.06, 6.78, 4.68, 11.21, 3.45, all P<0.001). The levels of CD3 +, CD4 + and CD4 +/CD8 + were enhanced significantly in the two groups, and the observation group had higher levels after treatment ( t values were 2.10, 3.74, and 5.19; P values were 0.028, <0.001, and <0.001). After 1 year of follow-up, the survival rate in observation group with 59.62% (31/52) was significantly higher than 37.78% (17/45) in control group ( χ2=4.60, P=0.032). The progression-free survival time ((10.22±1.62) months vs (8.13±1.57) months, t=6.43, P<0.001) and overall survival time ((11.62±1.84) months vs (9.73±1.71) months, t=5.21, P<0.001) in observation group were significantly longer compared to control group. There were no statistical differences in the incidence rates of bone marrow suppression ( χ2=1.92, P=0.165), hand-foot syndrome ( χ2=3.47, P=0.062), gastrointestinal reaction ( χ2=0.32, P=0.574), hypertension ( χ2=0.94, P=0.333) and proteinuria ( χ2=2.39, P=0.122) between the two groups. Conclusion:Compared with chemotherapy, pembrolizumab combined with apatinib shows good short-term efficacy and long-term efficacy in patients with HER2-negative advanced gastric cancer.

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