1.Exploring Mechanism of Hei Xiaoyaosan Regulating PI3K/Akt Pathway to Improve Learning and Memory Ability of Insomnia Rats with Liver Depression Syndrome Based on Transcriptomics
Jiamin LIU ; Yale WANG ; Hai HUANG ; Yue LI ; Xin FAN ; Pengpeng LIANG ; Shizhao ZHANG ; Mei YAN ; Guiyun LI ; Hongyan WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):114-125
ObjectiveBased on transcriptomics, to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group, model group, eszopiclone group (0.09 mg·kg-1), and low, medium, and high dose groups of Hei Xiaoyaosan (3.82, 7.65, 15.30 g·kg-1), with ten rats in each group. Except for the blank group, the other groups were induced insomnia rat model with liver depression by chronic restraint, tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine (PCPA). Each treatment group received intragastric administration according to the specified dosage, once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test, open field test, and Morris water maze test were used to test the sleep quality, depressive-like behavior, and learning and memory abilities of rats. Additionally, enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nitric oxide (NO) in hippocampus. Hematoxylin-eosin (HE) staining was performed to observe pathological changes of the hippocampal tissue, while terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group, as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the intersecting genes. Subsequently, the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was utilized to assess the mRNA expression levels of phosphatase and tensin homolog (PTEN), B-cell lymphoma-2 (Bcl-2)-like protein 11 (BCL2L11), and mitogen-activated protein kinase 1 (MAPK1) in hippocampus, and Western blot was employed to evaluate the protein expressions of PI3K, phosphorylation (p)-PI3K, Akt, p-Akt, Bcl-2, Bcl-2-associated X protein (Bax), and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group, the model group exhibited a reduction in body weight, an increase in sleep latency, and a decrease in sleep duration (P<0.01). Additionally, rats showed obvious depression-like behavior, and their learning and memory abilities decreased. Furthermore, the contents of 5-HT, GABA, NO, BDNF and GDNF in hippocampus decreased (P<0.01). Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus, characterized by irregular cell shapes, a reduced cell count, deeply stained and pyknotic nuclei, increased vacuolar degeneration, and an elevated apoptosis rate (P<0.01). Compared with the model group, the body weight of the high and medium dose groups of Hei Xiaoyaosan increased, the sleep latency shortened and the sleep time prolonged (P<0.05, P<0.01). Additionally, depression-like behavior and learning and memory abilities of rats were significantly improved, the levels of 5-HT, GABA, NO, BDNF and GDNF in the hippocampus increased (P<0.05, P<0.01). These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons (P<0.01). Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN, BCL2L11, and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group, the expression levels of PTEN, BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased (P<0.01), while the protein expression levels of p-PI3K, p-Akt and Bcl-2 were decreased (P<0.01), and the protein expression levels of PTEN, Bax and cleaved Caspase-3 were increased (P<0.01). Compared with the model group, the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN, BCL2L11 and MAPK1 mRNAs (P<0.01), up-regulate the expressions of p-PI3K, p-Akt and Bcl-2 proteins (P<0.01), and down-regulate the protein expressions of PTEN, Bax and cleaved Caspase-3 (P<0.05, P<0.01). ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN, BCL2L11 and MAPK1, and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.
2.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.
3.Tracking analysis of the relationship between isotemporal substitution of 24 h movement behavior and quality of life in children
SHE Gang, HUANG Jian, REN Limin, ZHANG Pengpeng
Chinese Journal of School Health 2024;45(9):1264-1268
Objective:
To explore the cross sectional and longitudinal relationships between children s 24 h movement behaviors and health related quality of life (HRQoL), and to reflect the impact of reallocating time between different activities on HRQoL scores using the isotemporal substitution analysis method, so as to provide a scientific basis for promoting children s health.
Methods:
In May 2022, a method combining cluster random sampling and convenience sampling was employed to conduct baseline survey on 397 children aged 7-10 from three primary schools in Wanzhou District of Chongqing. Children s movement behaviors were monitored using accelerometers, and their HRQoL was assessed through a health related quality of life questionnaire for children.The same questionnaire was used for assessing HRQoL of children on the follow up survery after on year(May 2023). A component based multiple linear regression model was used to analyze the relationship between children s 24 h movement behaviors and HRQoL.
Results:
The average daily times for children s light physical activity (LPA), moderate to vigorous physical activity (MVPA), sleep (SP), and sedentary behavior (SB) were (331.5±41.7,61.9±28.6,561.7±78.4,484.9±67.3) min, respectively. The mean baseline HRQoL score was (69.5±6.6), and it was (67.6±5.1) after one year. MVPA and SP were positively correlated with HRQoL at baseline( β =0.59,0.38) and after one year ( β =0.48, 0.39), while SB was negatively correlated with HRQoL at baseline and after one year ( β =-0.25, -0.53) ( P <0.05). An isotemporal substitution analysis showed that replacing 30 minutes of LPA or SB with MVPA increased the HRQoL scores by 1.81 and 2.79 at baseline, and by 1.37 and 2.12 after one year. Additionally, replacing SB with SP increased the HRQoL scores by 0.61 at baseline and by 0.39 after one year ( P <0.05).
Conclusions
Children s 24 h movement behaviors, particularly physical activity (PA) and sleep, are closely related to children s HRQoL. Appropriate measures should be taken to increase children s PA and SP time and reduce SB time to improve children s HRQoL.
4.Exploring Pharmacodynamic Material Basis and Mechanism of Hei Xiaoyaosan in Improving Learning and Memory Ability of Insomnia Rats Based on UPLC-Q-TOF-MS and Network Pharmacology
Jiamin LIU ; Hai HUANG ; Pengpeng LIANG ; Yale WANG ; Guiyun LI ; Hongyan WU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):19-30
ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology and pharmacodynamics, to investigate the pharmacodynamic material basis and mechanism of Hei Xiaoyaosan in improving learning and memory ability of insomnia rats. MethodUPLC-Q-TOF-MS was used to characterize the chemical constituents of Hei Xiaoyaosan. Network pharmacology was applied to construct the network of active ingredients-intersecting targets-pathways, and molecular docking was performed on key ingredients and core targets. Sixty 8-week-old male SD rats were selected and randomly divided into blank group, model group, Hei Xiaoyaosan low, medium, and high dose groups(3.82, 7.65, 15.30 g·kg-1), and zolpidem tartrate group(0.5 mg·kg-1), with 10 rats in each group. Except for the blank group, the insomnia model was induced by intraperitoneal injection of p-chlorophenylalanine(PCPA) for 4 consecutive days. Rats in each dosing group were administered the corresponding dose by gavage, once a day for 14 consecutive days. Morris water maze test was utilized to assess the learning and memory ability of rats, transmission electron microscopy was employed to examine the ultrastructure of hippocampal synapses, enzyme-linked immunosorbent assay(ELISA) was conducted to analyze the levels of 5-hydroxytryptamine(5-HT), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in hippocampal tissues, and Western blot was performed to detect the expression levels of tumor suppressor protein p53(TP53), rat sarcoma virus(RAS), epidermal growth factor receptor(EGFR), cyclic adenosine monophosphate(cAMP)-response element binding protein(CREB) binding protein(CREBBP), glycogen synthase kinase-3β(GSK-3β), protein kinase B1(Akt1), nitric oxide synthase 1(NOS1), phosphorylated(p)-Akt1, and p-GSK-3β in hippocampal tissues. Additionally, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to assess the mRNA expression levels of TP53, RAS, EGFR, CREBBP, GSK-3β, Akt1 and NOS1. ResultA total of 176 components were identified in Hei Xiaoyaosan, mainly flavonoids, triterpene saponins, phenylpropanoids and other compounds. Network pharmacological analysis revealed that TP53, V-Ha-Ras Harvey Rat sarcoma viral oncogene homolog(HRAS), neuroblastoma sarcoma viral oncogene homolog(NRAS), EGFR, CREBBP, GSK-3β, Akt1 and NOS1 were the key targets of Hei Xiaoyaosan in treating insomnia. The core targets were predominantly associated with cAMP, RAS, Ras-associated protein 1(Rap1), advanced glycation end products(AGE)/receptor for AGE(RAGE), and EGFR signaling pathways, and the key active ingredients of Hei Xiaoyaosan in treating insomnia were 8-shogaol, ligustilide F, 6-gingerol, levistilide A and senkyunolide E. Animal experiment results demonstrated that Hei Xiaoyaosan medium and high dose groups significantly increased body weight, shortened sleep latency and prolonged sleep duration in insomnia rats(P<0.01), significantly decreased escape latency and increased platform crossing frequency(P<0.01), and improved the pathological changes of hippocampal synaptic ultrastructure. Meanwhile, the two groups could significantly elevate 5-HT level, Akt1 mRNA expression, Akt1 and p-Akt1 protein expression(P<0.01), reduce inflammatory factor levels(P<0.01), and down-regulate protein expression levels of TP53, RAS, NOS1, EGFR, CREBBP, GSK-3β and p-GSK-3β(P<0.01), as well as mRNA expression levels of TP53, RAS, NOS1, EGFR, CREBBP and GSK-3β in hippocampal tissues(P<0.01). ConclusionThis study determined that the five key active ingredients(8-shogaol, ligustilide F, 6-gingerol, levistilide A and senkyunolide E) in Hei Xiaoyaosan may improve the learning and memory ability of insomnia rats by regulating signaling pathways such as cAMP, RAS, and EGFR, providing an important reference for its mechanism research and clinical application.
5.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.
6.Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor T therapy.
Zixun YAN ; Li LI ; Di FU ; Wen WU ; Niu QIAO ; Yaohui HUANG ; Lu JIANG ; Depei WU ; Yu HU ; Huilai ZHANG ; Pengpeng XU ; Shu CHENG ; Li WANG ; Sahin LACIN ; Muharrem MUFTUOGLU ; Weili ZHAO
Frontiers of Medicine 2023;17(4):699-713
Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.
7.BRICS report of 2021: The distribution and antimicrobial resistance profile of clinical bacterial isolates from blood stream infections in China
Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Jiliang WANG ; Hui DING ; Haifeng MAO ; Yizheng ZHOU ; Yan JIN ; Yongyun LIU ; Yan GENG ; Yuanyuan DAI ; Hong LU ; Peng ZHANG ; Ying HUANG ; Donghong HUANG ; Xinhua QIANG ; Jilu SHEN ; Hongyun XU ; Fenghong CHEN ; Guolin LIAO ; Dan LIU ; Haixin DONG ; Jiangqin SONG ; Lu WANG ; Junmin CAO ; Lixia ZHANG ; Yanhong LI ; Dijing SONG ; Zhuo LI ; Youdong YIN ; Donghua LIU ; Liang GUO ; Qiang LIU ; Baohua ZHANG ; Rong XU ; Yinqiao DONG ; Shuyan HU ; Kunpeng LIANG ; Bo QUAN ; Lin ZHENG ; Ling MENG ; Liang LUAN ; Jinhua LIANG ; Weiping LIU ; Xuefei HU ; Pengpeng TIAN ; Xiaoping YAN ; Aiyun LI ; Jian LI ; Xiusan XIA ; Xiaoyan QI ; Dengyan QIAO ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2023;16(1):33-47
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.
8.Application of single sperm sequencing for the preimplantation genetic testing of a Chinese family affected with Spinal muscular atrophy.
Jia CHEN ; Xingwu WU ; Ge CHEN ; Pengpeng MA ; Wan LU ; Zhihui HUANG ; Cailin XIN ; Yan ZHAO ; Qiongfang WU ; Yanqiu LIU
Chinese Journal of Medical Genetics 2023;40(2):148-154
OBJECTIVE:
To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M).
METHODS:
A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus.
RESULTS:
Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion.
CONCLUSION
By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.
Humans
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Pregnancy
;
Female
;
Child
;
Male
;
Preimplantation Diagnosis
;
East Asian People
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Semen
;
Genetic Testing
;
Muscular Atrophy, Spinal/genetics*
;
Aneuploidy
;
Blastocyst/pathology*
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High-Throughput Nucleotide Sequencing
;
Spermatozoa
9.The effect of radial extracorporeal shockwave therapy on scapulohumeral periarthritis in the elderly
Yun ZHOU ; Pengpeng HUANG ; Quanbing ZHANG
Chinese Journal of Geriatrics 2021;40(3):345-350
Objective:To investigate the clinical efficacy of radial extracorporeal shockwave therapy(ESWT)for scapulohumeral periarthritis in the elderly.Methods:A total of 82 patients diagnosed with scapulohumeral periarthritis at the rehabilitation medicine department of our hospital from July 2016 to January 2019 were retrospectively analyzed.The visual analogue score(VAS), Constant-Murley score(CMS), range of motion(ROM), adverse reactions, curative effectiveness and survival analysis were examined before treatment and at several time points within 6 months of treatment.Results:Compared with pre-treatment, the VAS, CMS, ROM, curative effects and survival analysis of patients with primary and secondary scapulohumeral periarthritis improved after treatment in both the conventional rehabilitation therapy group and the conventional rehabilitation therapy combined with ESWT group(all P<0.05). The short-term effects(2 weeks and 1 month after treatment)were better in the conventional rehabilitation therapy combined with ESWT group than in the conventional rehabilitation therapy group( P<0.05). There was no significant difference in long-term effects(2, 4 and 6 months after treatment)between the two groups( P>0.05). For patients with primary scapulohumeral periarthritis, conventional rehabilitation therapy combined with ESWT had advantages over conventional rehabilitation therapy in reducing the VAS score and improving shoulder function(CMS score and ROM)( P<0.05). For patients with secondary scapulohumeral periarthritis, conventional rehabilitation therapy combined with ESWT was better in reducing VAS than conventional rehabilitation therapy( P<0.05), while there was no significant difference in shoulder function improvement between the two groups(all P>0.05). Conclusions:Conventional rehabilitation combined with ESWT can relieve shoulder pain, improve range of motion and has a good safety profile in the treatment of scapulohumeral periarthritis in the elderly, but there is no significant difference in long-term efficacy between conventional rehabilitation therapy and conventional rehabilitation therapy combined with ESWT.
10.BRICS report of 2020: The bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China
Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Yuanyuan DAI ; Jiliang WANG ; Haifeng MAO ; Hui DING ; Yongyun LIU ; Yizheng ZHOU ; Hong LU ; Youdong YIN ; Yan JIN ; Hongyun XU ; Lixia ZHANG ; Lu WANG ; Haixin DONG ; Zhenghai YANG ; Fenghong CHEN ; Donghong HUANG ; Guolin LIAO ; Pengpeng TIAN ; Dan LIU ; Yan GENG ; Sijin MAN ; Baohua ZHANG ; Ying HUANG ; Liang GUO ; Junmin CAO ; Beiqing GU ; Yanhong LI ; Hongxia HU ; Liang LUAN ; Shuyan HU ; Lin ZHENG ; Aiyun LI ; Rong XU ; Kunpeng LIANG ; Zhuo LI ; Donghua LIU ; Bo QUAN ; Qiang LIU ; Jilu SHEN ; Yiqun LIAO ; Hai CHEN ; Qingqing BAI ; Xiusan XIA ; Shifu WANG ; Jinhua LIANG ; Liping ZHANG ; Yinqiao DONG ; Xiaoyan QI ; Jianzhong WANG ; Xuefei HU ; Xiaoping YAN ; Dengyan QIAO ; Ling MENG ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2021;14(6):413-426
Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.


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