1.Mechanism of Tumor T Cell Exhaustion from Perspective of ''Sanjiao-Yingwei'' Qi Transformation Malfunction
Xinhao TANG ; Bowen CHU ; Yuanyuan QIN ; Yeling LIU ; Xinyan SHU ; Mianhua WU ; Gang YIN ; Jianguo DAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):176-185
In order to promote the innovative application of Sanjiao theory and Yingwei theory, this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases, integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body, and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi, and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion, which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis, which contributes to T cell exhaustion and is correlated with nutrient deprivation, lipid accumulation, and high lactate levels in the immunosuppressed tumor microenvironment, as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction, Shengming decoction, and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation, and hypoxia inducible factor-1α (HIF-1α) may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.
2.Morphological study of GABAergic neurons in the ventral zona incerta of mice involved in chronic itch
Shihao PENG ; Ze FAN ; Ziyi DAI ; Yiwen ZHANG ; Xiaotong SHI ; Yuanyuan ZHU ; Shengxi WU ; Jing HUANG
Chinese Journal of Neuroanatomy 2024;40(1):1-8
Objective:To detect itching,anxiety,depression behaviors in chronic itch models of mice and observe the activation of γ-aminobutiric acid(GABA)neurons in the ventral sector of the zona incerta(ZIv),and provide mor-phological evidence for their involvement in the modulation of itch information.Methods:Diphenylcyclopropenone(DCP)was used in glutamic acid decarboxylase 67-green fluorescent protein(GAD67-GFP)knock-in mice to establish chronic itch model.Itch behaviors were detected by video tracking system to verify whether the models were successfully established.The anxiety,depression behaviors of chronic itch model mice were detected by using elevated plus maze test(EPM)and tail suspention test(TST).By using GAD67-GFP mice,the distribution of GABAergic neurons in va-rious sectors of the zona incerta(ZI)was observed.And combined with immunofluorescence staining method,double labeling of GABAergic neurons with FOS in ZIv were observed respectively in control and DCP group mice.Results:In brain slices of GAD67-GFP mice,GABAergic neurons can be observed within all sectors of ZI and are more concentrat-ed in ZIv.Compared with control group mice,DCP group mice showed a significant increase in the bouts of scratching(P<0.001).The time of immobility in TST was significantly higher in DCP group mice than in control group mice,which displayed depression-like behavior.The EPM test showed that the numbers of entries and proportion of time in the cross region in DCP group mice were less than in control group mice.EPM test revealed that DCP group mice exhibited anxiety-like behavior.The results of immunofluorescence staining showed that the number of FOS-positive cells in ZIv was significantly higher in DCP group mice than in control group mice,and abundant co-labeled neurons of FOS and GABAergic neurons were observed in ZIv.Conclusion:GABAergic neurons were predominantly distributed in ZI,and were more concentrated in ZIv.The activation of GABAergic neurons in ZIv of DCP group mice provides morphological evidence on the involvement of GABAergic neurons in chronic itch and associated negative emotions.
3.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
4.Risk prediction models of dangerous behaviors among patients with severe mental disorder in community
Xuanyi HU ; Min XIE ; Siyi LIU ; Yulu WU ; Xiangrui WU ; Yuanyuan LIU ; Changjiu HE ; Guangzhi DAI ; Qiang WANG
Sichuan Mental Health 2024;37(1):39-45
BackgroundThe occurrence rate of dangerous behaviors in patients with severe mental disorders is higher than that of the general population. In China, there is limited research on the prediction of dangerous behaviors in community-dwelling patients with severe mental disorders, particularly in terms of predicting models using data mining techniques other than traditional methods. ObjectiveTo explore the influencing factors of dangerous behaviors in community-dwelling patients with severe mental disorders and testing whether the classification decision tree model is superior to the Logistic regression model. MethodsA total of 11 484 community-dwelling patients with severe mental disorders who had complete follow-up records from 2013 to 2022 were selected on December 2023. The data were divided into a training set (n=9 186) and a testing set (n=2 298) in an 8∶2 ratio. Logistic regression and classification decision trees were separately used to establish predictive models in the training set. Model discrimination and calibration were evaluated in the testing set. ResultsDuring the follow-up period, 1 115 cases (9.71%) exhibited dangerous behaviors. Logistic regression results showed that urban residence, poverty, guardianship, intellectual disability, history of dangerous behaviors, impaired insight and positive symptoms were risk factors for dangerous behaviors (OR=1.778, 1.459, 2.719, 1.483, 3.890, 1.423, 2.528, 2.124, P<0.01). Being aged ≥60 years, educated, not requiring prescribed medication and having normal social functioning were protective factors for dangerous behaviors (OR=0.594, 0.824, 0.422, 0.719, P<0.05 or 0.01). The predictive effect in the testing set showed an area under curve (AUC) of 0.729 (95% CI: 0.692~0.766), accuracy of 70.97%, sensitivity of 59.71%, and specificity of 72.05%. The classification decision tree results showed that past dangerous situations, positive symptoms, overall social functioning score, economic status, insight, household registration, disability status and age were the influencing factors for dangerous behaviors. The predictive effect in the testing set showed an AUC of 0.721 (95% CI: 0.705~0.737), accuracy of 68.28%, sensitivity of 64.46%, and specificity of 68.60%. ConclusionThe classification decision tree does not have a greater advantage over the logistic regression model in predicting the risk of dangerous behaviors in patients with severe mental disorders in the community. [Funded by Chengdu Medical Research Project (number, 2020052)]
5.Clinical Efficacy and Effect on NLR of Tongfu Xiezhuo Enema in Treating Patients with Stage 3-4 CKD Based on Theory of Gut-kidney Axis
Yonghao SANG ; Liqun SONG ; Jie YUN ; Lijuan DAI ; Zeyang DIAO ; Yuanyuan DANG ; You XIONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):227-233
ObjectiveTo observe the clinical efficacy of Tongfu Xiezhuo enema in treating stage 3-4 chronic kidney disease (CKD) and the effect of the therapy on the neutrophil-to-lymphocyte ratio (NLR) as an inflammation marker. MethodSixty patients diagnosed with stage 3-4 CKD who visited the Nephrology Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from December 2022 to June 2023 were included and randomly assigned into observation and control groups in a ratio of 1∶1. The control group received conventional therapy plus Shenkang suppositories, while the observation group received conventional therapy plus Tongfu Xiezhuo enema. After 8 weeks of treatment, the clinical efficacy was assessed based on the changes in traditional Chinese medicine (TCM) symptom scores, renal function indicators, and NLR. Result① Both groups showed decreases in TCM symptom scores after treatment (P<0.01), and the decreases were more significant in the observation group than in the control group (P<0.05). The total response rate of TCM symptoms in the observation group was 79.31% (23/29), which was higher than that (62.96%, 17/27) in the control group (Z=0.604,P<0.05). ② After treatment, the observation group showed declined serum levels of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C (Cys C) and increased glomerular filtration rate (GFR) (P<0.01), and the control group showed lowered SCr level and increased GFR (P<0.05). The observation group had lower SCr level and higher GFR than the control group after treatment (P<0.05). The total response rate of renal function in the observation group was 79.31% (23/29), which was higher than that (55.56%, 15/27) in the control group (Z=1.127,P<0.01). ③ The NLR in the observation group decreased after treatment (P<0.05), and it was lower than that in the control group (P<0.05). ④ There were no significant differences in safety indicators between the two groups before and after treatment. ConclusionTongfu Xiezhuo enema ameliorated symptoms and improved renal function indicators in the patients with stage 3-4 CKD by reducing the NLR and inhibiting inflammation.
6.Progress on familial acute necrotizing encephalopathy
Shun WANG ; Chao DAI ; Danqun JIN ; Yuanyuan XU
International Journal of Pediatrics 2024;51(8):558-562
Familial acute necrotizing encephalopathy,also known as acute necrotizing encephalopathy type 1(ANE1),is a rapidly progressing rare encephalopathy with high morbidity and mortality rates.Although the etiology and pathogenesis remain unclear,mutations in genes such as RANBP2 and CPTⅡ are known to be related to its occurrence and development.Additionally,pathogen infections and cytokine storms are also considered potential influencing factors.Compared to isolated acute necrotizing encephalopathy,the clinical manifestations of ANE1 are more diverse,making diagnosis and treatment more complex.Currently,there are no specific therapeutic strategies for ANE1,and the effectiveness of immunomodulatory therapy remains controversial.Mitochondrial cocktail therapy and interleukin inhibitors have shown some therapeutic potential.The prognosis for ANE1 is generally poor,with survivors likely to experience severe neurological deficits and have a risk of recurrence.Early diagnosis and treatment are crucial for improving prognosis.
7.Medial prefrontal cortex neurons are involved in diphenylcycloacrylonone induced itch in mice
Jingwen LIU ; Yuanyuan ZHU ; Ziyi DAI ; Jing HUANG ; Zhantao BAI
Chinese Journal of Neuroanatomy 2024;40(2):137-144
Objective:To establish contact dermatitis pruritus model and detect itch,anxiety and depression-like behaviors.To observe the activation of the medial prefrontal cortex(mPFC)neurons and provide morphological evi-dence for its involvement in the regulation of itch perception information.Methods:A model of contact dermatitis pruri-tus was constructed with diphenylcyclopyrenone(DCP)applied on the neck and back of the mouse,and the itch per-ception video tracking system was used to detect the scratching behavior.Open field and suspended tail behavioral ex-periments were conducted to explore the anxiety and depression-like behaviors of mice under contact dermatitis.The dis-tribution of c-Fos and p-ERK1/2 positive cells in the mPFC of contact dermatitis model mice was investigated by immu-nofluorescence staining.Results:The contact dermatitis pruritus model was successfully established,and the bouts of scratching in the contact dermatitis model group was significantly higher than that in the control group(P<0.05).The results of open field test showed that the time and distances were significantly reduced in the central area of the contact dermatitis model group.The results of the tail suspension experiment suggested that the time of immobility increased sig-nificantly in the contact dermatitis model group(P<0.05).There were more c-Fos positive and p-ERK1/2 positive cells in the mPFC compared with the control group(P<0.05).Conclusion:Bouts of scratching were increased in the contact dermatitis group and the mice had anxiety and depression-like behaviors.In the contact dermatitis state,mPFC neurons were activated,providing morphological evidence for the involvement of mPFC neurons in contact dermatitis pruritus and accompanying affective disorders such as anxiety and depression.
8.Research progress on ferroptosis in sepsis-induced liver injury
Chengzhu XU ; Danqun JIN ; Chao DAI ; Yuanyuan XU
Chinese Journal of Applied Clinical Pediatrics 2024;39(11):877-880
In recent years, as researchers delve deeply into the cell death mechanisms, ferroptosis, as a new iron-dependent cell death mode, has gradually become a research hotspot.It is mainly triggered by iron overload and lipid peroxidation in organisms.Sepsis-induced liver injury is an important pathophysiological process in the systemic inflammatory response caused by infection, which is closely related to various cell death modes.This review aims to explore the research progress on ferroptosis in sepsis-induced liver injury, including the mechanism of ferroptosis occurrence in sepsis-induced liver injury, its relationship with sepsis-induced liver injury, and possible therapeutic strategies for ferroptosis.
9.Exercise rehabilitation experience of stroke patients:a qualitative meta-synthesis
Huiling SHI ; Qing WANG ; Yuanyuan JIANG ; Min ZHANG ; Yuting DAI ; Kangling JI
Chinese Journal of Nursing 2024;59(11):1397-1404
Objective To systematically evaluate the qualitative research on the experience and feeling of elderly patients with hip fracture during rehabilitation.Methods We searched databases including the PubMed,Embase,Web of Science,Cochrane Library,CNAIHL,CNKI,Wanfang,VIP,SinoMed.The literature of qualitative research on the exercise rehabilitation experience of stroke patients from the establishment of the database to August 17,2023 was retrieved.Results A total of 59 clear research topics were extracted,and 14 new categories were formed after induction and integration,which were finally merged into 5 integrated results.Integration results 1:Perceived benefits of exercise rehabilitation.Integration results 2:Multiple driving forces of exercise rehabilitation.Integration results 3:Gradual loss of patience in long-term rehabilitation.Integrated results 4:Generating new rehabilitation needs and actively coping with them.Integrated results 5:There are many difficulties in carrying out self-rehabilitation.Conclusion During the process of exercise rehabilitation for stroke patients,medical personnel should pay attention to the patients'actual feelings,inner needs,and the practical challenges they face in participating in exercise rehabilitation.Personalized exercise rehabilitation facilitation strategies should be developed for stroke patients,aiming for the scientific and precise advancement of exercise rehabilitation,and ultimately improving long-term rehabilitation outcomes for patients.
10.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

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