1.Identification of Cuproptosis-related Biomarkers in Alzheimer's Disease Based on Bioinformatics and Machine Learning and Clinical Validation and Prediction of Potential Traditional Chinese Medicine
Guofang YU ; Chenling ZHAO ; Liwei TIAN ; Wenming YANG ; Ting DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):160-167
ObjectiveThis study aims to identify cuproptosis-related gene biomarkers in Alzheimer's disease(AD) using bioinformatics and machine learning methods, validate them at the clinical specimen level, and predict potential traditional Chinese medicine(TCM). MethodsDifferentially expressed genes in the AD group and normal group were obtained using the Gene Expression Omnibus (GEO) database, and intersections were taken with reported cuproptosis-related genes to obtain differentially expressed cuproptosis-related genes. Machine learning methods were applied to identify core differential genes of cuproptosis in AD. Peripheral blood's single nucleated cells from clinical AD patients were collected, and the relative gene expression was clinically verified by real-time polymerase chain reaction(Real-time PCR). Potential TCM regulating cuproptosis for AD were predicted by COREMINE database. ResultsA total of 12 cuproptosis-related genes were obtained, mainly involved in pathways of tricarboxylic acid cycle, 2-oxocarboxylic acid metabolism, and carbon metabolism. Five core cuproptosis-related genes, dihydrolipoamide dehydrogenase (DLD), glutaminase (GLS), pyruvate dehydrogenase E1 subunit beta (PDHB), full name nuclear factor (erythroid-derived 2)-related factor 2 (NFE2L2), and dihydrolipoamide branched-chain transacylase E2 (DBT) were finally screened using four machine methods. Thirty cases each of normal and AD patients were collected clinically. Compared with those in the normal group, minimum mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were significantly decreased in the AD group (P<0.01), Homocysteine(Hcy), interleukin(IL)-6, C-reactive protein(CRP) , and β amyloid protein(Aβ) indexes were significantly increased (P<0.01), and malondialdehyde(MDA) indexes were decreased (P<0.05). Superoxide dismutase(SOD) levels were significantly decreased (P<0.01). The mRNA relative expressions of NFE2L2 and DBT were up-regulated (P<0.05), and those of DLD, GLS, and PDHB were significantly down-regulated (P<0.01). The TCM regulating cuproptosis-related genes for the treatment of AD were mainly based on the four Qi such as warmth, calmness, and cold, and the five flavors including bitterness, sweetness, and pungency, and it was attributed to the meridians of the liver, spleen, stomach, and kidney, with the efficacy of tonifying Qi, activating blood, eliminating phlegm, and resoling dampness. ConclusionDLD, GLS, NFE2L2, PDHB, and DBT can be used as novel diagnostic molecular markers for AD cuproptosis-related genes, and the corresponding potential therapeutic TCM can provide new ideas for the treatment of AD by TCM.
2. Network pharmacology-based study on mechanism of Zhi-Huang-Zhi-Tong powder in rheumatoid arthritis treatment
Xiao-Yun TIAN ; Ying-Jie YANG ; Wan-Ting ZHENG ; Ming-Qing HUANG ; Li-Hong NAN ; Jian-Yu CHEN ; Hai-Yu ZHAO
Chinese Pharmacological Bulletin 2024;40(2):381-389
Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.
3.Effect of stage Ⅰ comprehensive cardiac rehabilitation in patients with acute ST elevation myocardial infarctionafter emergency percutaneous coronary intervention
Yue REN ; Ting TIAN ; Guangsheng WEI ; Ming ZHANG ; Hong YU ; Jie LI ; Tingting DONG ; Yinmei FENG ; Hongchao CUI ; Jiao ZHANG
The Journal of Practical Medicine 2024;40(5):682-687
Objective This study aimed to investigate the effect of stage Ⅰ comprehensive cardiac rehabili-tation in patients with acute ST elevation myocardial infarction(STEMI)after emergency percutaneous coronary intervention(PCI).Methods A total of 72 patients with acute ST-segment elevation myocardial infarction combined with PCI admitted to the Department of Cardiovascular Medicine of Beijing Electric Power Hospital of State Grid Corporation from June 2021 to June 2022,which were selected as the research objectsand divided into control group and observation group randomly(36 cases in each group).The control group was treated with routine nursing and health education,and the observation group with stage Ⅰ comprehensive cardiac rehabilitation,including initial assessment(cardiovascular comprehensive assessment),exercise training(exercise training and breathing train-ing),daily activity suggestions and health education,discharge assessment(six-minute walking test and Barthel index assessment).The score of Barthel index(BI)at discharge,the 6-minute walking test distance(6MWD)at discharge,the incidence of major adverse cardiovascular event(MACE)during hospitalization and within one month of discharge,and the length of stay were compared between the two groups.Results After intervention,the six-minute walking test distance(6MWD)and Barthel index(BI)score in the observation group were better than those in the control group,the difference was statistically significant(P<0.05).The incidence of major adverse cardiovascular events(MACE)during hospitalization and one month after discharge was lower in the observation group than in the control group,and the difference was statistically significant(P<0.05).The length of hospital-ization in observation group was lower than that in control groupbut there was no statistical difference(P>0.05).Conclusion The application of phase Ⅰ comprehensive cardiac rehabilitation training in patients with acute ST-segment elevation myocardial infarction combined with emergency PCI could improve the patients'exercise ability,improve their ability of daily activity,reduce the incidence of major adverse cardiovascular events(MACE)in the early stage of the disease,facilitate the patients to return to their families and society as soon as possible,and improve their quality of life.It has high clinical application value.
4.The effects of Epimedium koreanum Nakai on liver function in rats with kidney yang deficiency and kidney yin deficiency pattern models based on the"You Gu Wu Yun"theory
Xiyi PENG ; Lin ZHANG ; Yuqi ZHAI ; Shuwei YU ; Yuan TIAN ; Zhaojuan GUO ; Song YANG ; Ting WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1562-1572
Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.
5.Low frequency transcranial magnetic stimulation can improve upper limb motor function in the acute phase of ischemic stroke
Tian SUN ; Zunke GONG ; Ting ZHOU ; Yonggang ZHU ; Tong SU ; Wenqi TANG ; Jie YU ; Xiuhua ZHU
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(3):216-220
Objective:To explore the utility of applying low frequency transcranial magnetic stimulation (rTMS) in the acute stage of ischemic stroke in terms of improving upper limb motor function.Methods:Eighty ischemic stroke survivors in the acute stage were randomly divided into a control group and an experimental group, with 40 in each. In addition to routine rehabilitation, the experimental group was given low frequency rTMS, while the control group was provided with sham rTMS. Before and after 4-weeks of treatment, upper limb motor function was evaluated using the Fugl-Meyer rating scale (FMA), Wolf motor function tests (WMFTs), the modified Barthel index (MBI) and in terms of motor evoked potential (MEP) latency and amplitude.Results:There were no significant differences between the two groups before the treatment. Afterward, however, the average FMA, WMFT, MBI scores had improved significantly more in the experimental group, on average, as had the average MEP amplitude.Conclusion:Low frequency rTMS in the acute phase of ischemic stroke can improve upper limb motor function and ability in the activities of daily living.
6.Prevalence of Echinococcus infections in small rodents in Yushu City, Qinghai Province in 2023
Gengcheng HE ; Shusheng WU ; Xianglan QIN ; Jilong MA ; Tingjun YU ; Chengxi SONG ; Xiaojin MO ; Xiao MA ; Jianfeng BA ; Guirong ZHENG ; Bin JIANG ; Tian TIAN ; Shijie YANG ; Ting ZHANG ; Xiaonong ZHOU
Chinese Journal of Schistosomiasis Control 2024;36(2):169-173
Objective To investigate the prevalence of Echinococcus infections in small rodents around human residential areas in Yushu City, Qinghai Province in 2023, so as to provide insights into precision echinococcosis control. Methods One or two quadrats, each measuring 50 m × 50 m, were randomly assigned in Shanglaxiu Township and Longbao Township, Yushu City, Qinghai Province on June 2023, respectively, and 300 plate-type mouse traps, each measuring 12.0 cm × 6.5 cm, were assigned in each quadrat. Small rodents were captured during the period between 10 : 00 and 18 : 00 each day for 4 days. Then, all captured small rodents were identified and dissected, and liver specimens with suspected Echinococcus infections were subjected to pathological examinations. The Echinococcus cytochrome c oxidase 1 (cox1) gene was amplified using PCR assay, and the sequence of the amplified product was aligned to that was recorded in the GenBank to characterize the parasite species. In addition, a phylogenetic tree of Echinococcus was generated based on the cox1 gene sequence using the neighbor-joining method. Results A total of 236 small rodents were captured in Shanglaxiu and Longbao townships, Yushu City, including 65 Qinghai voles and 51 plateau pikas in Shanglaxiu Township, and 62 Qinghai voles and 58 plateau pikas in Longbao Township, and there was no significant difference in the constituent ratio of small rodents between the two townships (χ2 = 0.294, P > 0.05). Seven plateau pikas and 12 Qinghai voles were suspected to be infected with Echinococcus by dissection, and pathological examinations showed unclear structure of hepatic lobules and disordered hepatocyte arrangement in livers of small rodents suspected of Echinococcus infections. PCR assay identified E. shiquicus DNA in 7 Qinghai voles, which were all captured from Shanglaxiu Township. Phylogenetic analysis showed that the cox1 gene sequence of Echinococcus in small rodents was highly homologous to the E. shiquicus cox1 gene sequence reported previously. Conclusion Plateau pika and Qinghai vole were predominant small rodents around human residential areas in Yushu City, Qinghai Province in 2023, and E. shiquicus infection was detected in Qinghai voles.
7.Practice and evaluation of hospital antimicrobial stewardship empowered by digital intelligence technology
Li-Mian LIANG ; Yun-Ni YU ; Miao-Na LIU ; Ting HUANG ; Yi-Mei TIAN
Chinese Journal of Infection Control 2024;23(3):330-335
Objective To improve the efficiency of hospital antimicrobial management and ensure rational clinical use of antimicrobial agents with the aid of antimicrobial stewardship(AMS)empowered by digital intelligence tech-nology in hospital.Methods Information systems such as early warning of antimicrobial indexes,closed-loop ma-nagement of microbial detection information,and decision-making system of antimicrobial resistance monitoring data were applied to the traditional AMS system.Through hospital information systems(HIS)to collect data about thera-peutic antimicrobial use and healthcare-associated infection(HAI)quality control indexes of hospitalized patients in a tertiary first-class public hospital in Shenzhen City before and after digital technology improvement,indexes of 2021 and 2022 were as control group(before improvement)and observation group(after improvement)respective-ly,improvement trend of antimicrobial management was compared.Results After upgrading and renovating the hospital information system,hospital antimicrobial management indexes improved significantly compared to before the renovation.The use rate of antimicrobial agents and the preventive use rate of antimicrobial agents in class Ⅰincision surgery in patients in the observation group were both lower than those in the control group(27.0%vs 38.8%,20.9%vs 23.8%,respectively,both P<0.05).Antimicrobial use density in hospitalized patients in the observa-tion group was lower than that in the control group([33.27±3.03]DDDs vs[42.06±4.42]DDDs),difference was statistically significant(t=13.11,P<0.001).The observation group had a higher qualified rate for evaluating antimicrobial medical orders compared to the control group(98.5%vs 96.8%).The pathogenic detection rate of hospitalized patients before therapeutic antimicrobial use and pathogen detection rate related to HAI diagnosis were both higher than those in the control group(87.1%vs 84.5%,99.0%vs 95.4%,respectively),differences were both statistically significant(both P<0.05).Conclusion Empowering the hospital's AMS system with digital technology can promote more scientific,standardized,efficient,and rational antimicrobial management in hospitals.
8.Discrete element modeling and breakage behavior analysis of oral solid dosage form particles
Lin-xiu LUO ; Tian-bing GUAN ; An-qi LUO ; Zeng LIU ; Yu-ting WANG ; Yan-ling JIANG ; Zheng LU ; Jing-cao TANG ; Shuang-kou CHEN ; Hui-min SUN ; Chuan-yun DAI
Acta Pharmaceutica Sinica 2024;59(4):1057-1066
The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.
9.Study on Evidence-Based Decision-Making of Acupuncture for Post-Prostatectomy Urinary Incontinence: based on TOPSIS Combined with Entropy Method
Zhiwei DONG ; Junlan WANG ; Tao XIE ; Yanying YE ; Ting LI ; Cong YU ; Ning TIAN
Journal of Traditional Chinese Medicine 2024;65(23):2434-2441
ObjectiveTo screen optimized protocol of acupuncture for post-prostatectomy urinary incontinence (PPUI) patients, and to provide evidence for clinical practice. MethodsMEDLINE, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, WanFang and VIP databases were searched to collect randomized controlled trials of acupuncture for PPUI. The search was conducted from the establishment of the database to February 1, 2024, and the quality of the literature was evaluated to exclude the studies with a high risk of overall bias or modified Jadad <3, and constructed acupuncture protocol and performed meta-analysis. We used International Consultation on Urinary Incontinence Short Form (ICI-Q-SF) scores, quality of life scores, overall effective rate, and modified Jadad scores as beneficial indicators, and the number of acupoints selected, stimulation duration, the number of acupuncture, and the duration of the treatment course as costly indicators, to derive the standardized protocol matrix, and used the entropy method to determine the weights of the different decision-making indicators, and finally combined with the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for comprehensive evaluation. ResultsNine studies met the criteria, and the acupuncture treatments involved were constructed as six protocols including electrical acupoint stimulation with low-frequency, electroacupuncture at four acupoints of sacral region, replenishing qi and tonifying kidney acupuncture, body acupuncture plus pelvic floor muscle training, auricular acupuncture, and electroacupuncture plus pelvic floor muscle training. The ICI-Q-SF, number of acupuncture sessions, and total effectiveness rate were given higher weights in the decision-making indexes, while the stimulation duration and the duration of treatment course were given lower weights; the entropy method of TOPSIS was used for the evaluation and proved that the best protocol was the electroacupuncture at four acupoints of sacral region which used continuous-wave electroacupuncture with a frequency of 2 Hz for 60 min each time, and required the needle sensation to radiate to the root of the penis, with the advantages of streamlined selection of acupoints, a significant reduction in ICI-Q-SF, and an increase in the effectiveness rate. ConclusionThe final optimized protocol was electroacupuncture at four acupoints of sacral region, which can provide an evidence-based basis for clinical decision-making and guideline development.
10.Design of GIS-based 3D playback system for flight human-plane data
La-Mei SHANG ; Yu-Fei QIN ; Wen WANG ; Wan-Qi LI ; Da-Long GUO ; Xiao-Chao GUO ; Juan LIU ; Zhen TIAN ; Ting-Ting CUI ; Yu-Bin ZHOU
Chinese Medical Equipment Journal 2024;45(10):14-19
Objective To develop a GIS-based 3D playback system for the flight human-plane data to realize the fusion of pilots'airborne flight data and physiological data.Methods The 3D playback system was developed with the Browser/Server(B/S)architecture,micro-server model,Java language and Spring Cloud technology framework,which was composed of three functional modules for flight process reproduction,physiological situational awareness and critical event calibration analysis.Results The system developed achieved time synchronization and data fusion of airborne flight data and physiological data with a time synchronization frequency of 1 Hz and a refresh rate of not less than 120 frames/s.Conclusion The system developed with high safety,stability,reliability and accuracy facilitates pilot in-flight physiological monitoring and fusion and simultaneous display of airborne flight data and physiological data,which can be used as an important platform for decision-making support in flight training.[Chinese Medical Equipment Journal,2024,45(10):14-19]

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