1.The Development of Chinese Herbal Formulae for Non-severe COVID-19 Based on Artificial Intelligence Technology and Investigation of Its Action Mechanisms
Wenting HUANG ; Liansheng QIAO ; Di YAN ; Tengwen LIU ; Hongmei CAO ; Hongyan GUO ; Zhi ZHANG ; Jing CHENG ; Lan XIE ; Qingquan LIU
Journal of Traditional Chinese Medicine 2024;65(1):103-112
ObjectiveTo develop traditional Chinese medicine (TCM) formulae for the treatment of nonsevere coronavirus disease 2019 (COVID-19) and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways, and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China, a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19, the calculation was carried out, and the artificial intelligent methods for compositing formulae, that are exhaustive method and parallel computing, were used to obtain candidate compound formulas. Finally, with reference to professional experience, an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b (Il1b), C-X-C motif chemokine ligand 2 (Cxcl2), C-X-C motif chemokine ligand 10 (Cxcl10), C-C motif chemokine ligand 2 (Ccl2), nitric oxide synthase 2 (Nos2), and prostaglandin-endoperoxide synthase 2 (Ptgs2) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in RAW264.7 cells treated with lipopolysaccharide (LPS). ResultsIn macrophages and lung epithelial cells, 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome, and the result showed that Yinqiao Powder and Pingwei Powder (银翘散合平胃散, YQPWP) ranked first, reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally, YQPWP had the function of scattering wind and clearing heat, resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula, and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin (翘蒡术皮饮, QBZPY) based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells, with the reversing rates of 100%. The chief medicinal of QBZPY, including Lianqiao (Fructus Forsythiae), Xixiancao (Herba Siegesbeckiae) and Niubangzi (Fructus Arctii), can down-regulate multiple signaling pathways related with virus infection, immune response, and epithelial damage. RT-qPCR results indicated that compared with the model group, the QBZPY group down-regulated the mRNA expression of Il1b, tumor necrosis factor (Tnf), Cxcl2, Cxcl10, Ccl2, Nos2 and Ptgs2 induced by LPS in RAW264.7 cells (P<0.05 or P<0.01). ConclusionBased on targeted transcriptome analysis, expert experience in TCM and artificial intelligence, QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.
2.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
3.Data-independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sj?gren's Syndrome
Tian YI-CHAO ; Guo CHUN-LAN ; Li ZHEN ; You XIN ; Liu XIAO-YAN ; Su JIN-MEI ; Zhao SI-JIA ; Mu YUE ; Sun WEI ; Li QIAN
Chinese Medical Sciences Journal 2024;39(1):19-28,中插3
Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.
4.Evidence summary of early mobilization in awake patients on extracorporeal membrane oxygenation
Jiangshuyuan LIANG ; Fei ZENG ; Meijuan LAN ; Peipei GU ; Lingyun CAI ; Luyao GUO ; Yan ZHU ; Ge GUO
Chinese Journal of Nursing 2024;59(3):345-352
Objective To retrieve,evaluate and summarize the best evidence of early mobilization in awake patients on extracorporeal membrane oxygenation,and to provide a reference for clinical practice.Methods UpToDate,BMJ Best Practice,Registered Nurses'Association of Ontario,National Guideline Clearinghouse,National Institute for Health and Care Excellence,Yimaitong,Joanna Briggs Institute Library,Cochrane Library,CINAHL,PubMed,SinoMed,CNKI,Wanfang Database,Vip Database and Extracorporeal Life Support Organization Website were researched to collect the literature,including clinical guidelines,expert consensuses,evidence summaries,systematic reviews,and well-designed original studies.The time limit for retrieval was until June 2023.The quality of literature and the level of evidence were evaluated by the evaluation criteria and evidence grading system of J BI Evidence-Based Health Care Center.Results 14 pieces of the literature were included,including 2 clinical guidelines,4 expert consensuses,5 systematic reviews,2 cohort studies and 1 case series.Totally 33 pieces of evidence were summarized,covering 7 aspects:adaptation conditions for the implementation of awake ECMO,team composition,comprehensive assessment,pre-mobilization preparation,mobilization content,prevention and control of adverse events,and effect evaluation.Conclusion The study summarizes the best evidence of early mobilization in awake patients on extracorporeal membrane oxygenation.It is suggested that medical institutions establish a professional team for the early mobilization of awake ECMO patients,apply the best evidence to standardize the early mobilization process,and formulate an individualized mobilization program.
5.Correlation analysis on occupational acid fog exposure and accelerated biological aging in workers
Weichao WU ; Yan GUO ; Xiangkai ZHAO ; Zhiguang GU ; Yijia GUO ; Zipeng LAN ; Hui HUANG ; Lei KUANG ; Ming ZHANG ; Dongsheng HU ; Yongli YANG ; Wei WANG ; Jinru CHEN
Journal of Jilin University(Medicine Edition) 2024;50(6):1741-1750
Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.
6.Exploring the Characteristics of Congenital Circuit-Qi Endowment in Patients with Pneumonia of Shaoyin-Disease Syndrome Based on the Five-Circuit and Six-Qi Theory
Fu-Juan LAN ; Tao-Yu YANG ; Dang-Hong CHEN ; Guo-Feng XU ; Fang YAN ; Sui-He HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(11):2863-2868
Objective Based on the theory of five circuits and six qi,the characteristics of circuit-qi indicators of the date of birth of hospitalized patients with pneumonia of Shaoyin-disease syndrome were explored.Methods The data collection was conducted in 422 hospitalized patients with pneumonia of shaoyin-disease syndrome admitted to the Department of Classical Chinese Medicine,Fangcun Hospital of Guangdong Provincinal Hospital of Chinese Medicine from January 20,2012 to June 30,2022.And then statistical analysis was performed for circuit-qi indicators of the date of birth of the patients.Results The goodness of fit by chi-square test showed that there were statistically significant differences in the distribution of the heavenly-stem year,earthly-branch year,yearly circuit,recombinant yearly circuit,predominant qi,and sitian-zaiquan(circuit qi of the first and second half of a year)at birthdate of hospitalized patients with pneumonia of shaoyin-disease syndrome(P<0.05 or P<0.001).And the results indicated that a higher risk of suffering from pneumonia of shaoyin-disease syndrome existed in the population born in the heavenly-stem ji year and earthly-branch chou year,in the yearly circuit being deficient earth circuit,in the recombinant yearly circuit being wind,in the predominant qi being taiyin damp earth,and in the sitian-zaiquan being taiyin damp earth and taiyang cold-water.Conclusion There is a correlation between the incidence of pneumonia of shaoyin-disease syndrome and the circuit-qi indicators of the date of birth of the patients,and the pathogenesis of circuits and qi at birth date is probably related with yang deficiency of spleen and kidney,and cold interweaved with dampness.
7.Application efficacy of FMEA management model-based risk assessment in prevention and control of healthcare-associated infection:a Meta-analysis
Ling CAI ; Kang-Le GUO ; Yan WANG ; Ying-Hua ZHANG ; Yu-Qing FAN ; Xiao-Hong ZHANG ; Lan-Wen HU ; Ya-Hong YANG ; Hao-Jun ZHANG
Chinese Journal of Infection Control 2024;23(11):1350-1357
Objective To systematically evaluate the application efficacy of failure mode and effect analysis(FMEA)management mode in the prevention and control of healthcare-associated infection(HAI).Methods Li-terature on the application of FMEA management mode in HAI prevention and control were retrieved from PubMed,Embase,the Cochrane Library,China National Knowledge Infrastructure(CNKI),VIP Database,Wanfang Data-base,and China Biomedical Literature Database(CBM).Two researchers independently screened the literature,ex-tracted data,and conducted cross checking.Risk and quality assessments were performed on the included studies of randomized controlled trials by ROB tool,the included cohort studies were scored by Newcastle-Ottawa(NOS)scale,and Meta-analysis was conducted by RevMan 5.4 software.Results A total of 22 studies involving 42 815 patients were included in the analysis,with 21 784 in the FMEA management mode group and 21 031 in the control group.Meta-analysis results showed that the incidence of HAI in the FMEA management mode group was lower than that in the control group(OR=0.31,95%CI[0.24,0.40]).Compared with the conventional management mode,incidences of superficial surgical site infection(OR=0.53,95%CI[0.36,0.78]),respiratory system infec-tion(OR=0.44,95%CI[0.35,0.56]),urinary system infection(OR=0.45,95%CI[0.38,0.53]),and blood system infection(OR=0.29,95%CI[0.18,0.45])in the FMEA management mode group were all lower(all P<0.01).Conclusion The application of FMEA management mode in HAI prevention and control can reduce the inci-dence of HAI,which should be actively promoted in hospital management.
8.Meta-analysis on the incidence of long COVID in Omicron-infected pa-tients
Li-Yu WANG ; Shi-Wei WU ; Meng-Qi XU ; Bao-Guang LIU ; Lan-Ying PEI ; Guo-Li YAN ; Guan-Min ZHENG
Chinese Journal of Infection Control 2024;23(11):1384-1390
Objective To explore the incidence of long CO VID symptoms in patients infected with Omicron variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods According to the inclusion and exclu-sion criteria of literatures,relevant studies without language restrictions published up to 2024 were retrieved from both Chinese and English databases.The Chinese databases were China National Knowledge Infrastructure(CNKI),Wanfang Database,and VIP databases,and the foreign databases were PubMed,Embase,and Web of Science.Three-step screening was used to select literatures,and Stata 17.0 software was used for analysis.Results The incidence of at least one sequelae in patients infected with Omicron variant was 29.62%.The most common symptoms included fatigue(19.10%),joint or muscle pain(11.06%),memory loss(9.71%),brain fog(8.80%),cough(8.42%),headache(7.26%),and sore throat(6.68%).Subgroup analysis results showed that with the extension of follow-up(3 months vs 6 months),the incidence of smell or taste changes was significantly re-duced(7.22%vs 0.78%).The higher the proportion of women(<50%vs 50%-65%vs>65%),the higher the incidence of joint or muscle pain(1.09%vs 4.62%vs 19.53%);the greater the median age(≥45 years vs<45 years),the higher the incidence of chest pain or chest distress(0.90%vs 3.86%),all with statistically significant differences(all P<0.05).Conclusion Incidence of long COVID in Omicron-infected patients is high and can cause various symptoms.Follow-up time,median age and gender proportion have significant impacts on the incidence of some symptoms.
9.Mechanism of artemisinin inhibiting malignant biological behavior of colorectal cancer cells stimulated by glucose
Yong-Na PAN ; Yue-Feng CHANG ; Jing-Jing GUO ; Yi-Li SUN ; Lan WEI ; Chun-Yan YANG ; Jin-Wang KANG
Journal of Regional Anatomy and Operative Surgery 2024;33(5):388-393
Objective To investigate the effect of artemisinin(ART)on the malignant biological behavior of colorectal cancer(CRC)cells stimulated by glucose and its mechanism.Methods The concentration gradients of 0,5,10,20,40 and 60 μmol/L of ART were used to treat the human colorectal cancer cell line SW480,and then the cell viability was detected by CCK-8.Cell apoptosis was detected by flow cytometry.Transwell was used to detect the cell migration and invasion.Western blot was used to detect the apoptosis,epithelial-mesenchymal transition(EMT)and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)related proteins expression.Results Compared with the 0 μmol/L of ART,the viability of SW480 cells decreased under 5,10,20,40,60 μmol/L of ART treatment(P<0.05),and IC50 was 36.91 μmol/L.Therefore,the cells treated with 10,20 and 40 μmol/L of ART were as the low-dose,medium-dose and high-dose ART groups,the cells treated with 0 μmol/L of ART were as the control group,and the cells treated with 40 μmol/L of ART and 10 μmol/L of Coumermycin A1 were as the Coumermycin A1 group.Compared with the control group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the low-dose ART group,the medium-dose ART group,and the high-dose ART group decreased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin increased(P<0.05).Compared with the high-dose ART group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the Coumermycin A1 group increased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin decreased(P<0.05).Conclusion ART may inhibit the viability,migration,invasion and EMT of glucose-stimulated CRC cells and promote apoptosis by inhibiting the JAK2/STAT3 signaling pathway.
10.Analysis of Therapeutic Efficacy and Adverse Prognostic Factors of Secondary Central Nervous System Lymphoma
Ning WANG ; Fei-Li CHEN ; Yi-Lan HUANG ; Xin-Miao JIANG ; Xiao-Juan WEI ; Si-Chu LIU ; Yan TENG ; Lu PAN ; Ling HUANG ; Han-Guo GUO ; Zhan-Li LIANG ; Wen-Yu LI
Journal of Experimental Hematology 2024;32(5):1420-1426
Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01%and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3%and 61%,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

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