1.Quercetin Confers Protection against Sepsis-Related Acute Respiratory Distress Syndrome by Suppressing ROS/p38 MAPK Pathway.
Wei-Chao DING ; Juan CHEN ; Quan LI ; Yi REN ; Meng-Meng WANG ; Wei ZHANG ; Xiao-Hang JI ; Xin-Yao WU ; Shi-Nan NIE ; Chang-Bao HUANG ; Zhao-Rui SUN
Chinese journal of integrative medicine 2025;31(11):1011-1020
OBJECTIVE:
To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS).
METHODS:
In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro.
RESULTS:
Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01).
CONCLUSION
Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals
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Sepsis/drug therapy*
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Quercetin/therapeutic use*
;
Respiratory Distress Syndrome/enzymology*
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p38 Mitogen-Activated Protein Kinases/metabolism*
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Mice, Inbred C57BL
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Reactive Oxygen Species/metabolism*
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Apoptosis/drug effects*
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Male
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Oxidative Stress/drug effects*
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MAP Kinase Signaling System/drug effects*
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Lung/drug effects*
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Mice
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Lipopolysaccharides
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Macrophages, Alveolar/pathology*
;
Inflammation/pathology*
;
Protective Agents/therapeutic use*
2.PARylation promotes acute kidney injury via RACK1 dimerization-mediated HIF-1α degradation.
Xiangyu LI ; Xiaoyu SHEN ; Xinfei MAO ; Yuqing WANG ; Yuhang DONG ; Shuai SUN ; Mengmeng ZHANG ; Jie WEI ; Jianan WANG ; Chao LI ; Minglu JI ; Xiaowei HU ; Xinyu CHEN ; Juan JIN ; Jiagen WEN ; Yujie LIU ; Mingfei WU ; Jutao YU ; Xiaoming MENG
Acta Pharmaceutica Sinica B 2025;15(9):4673-4691
Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.
3.Development and application on a full process disease diagnosis and treatment assistance system based on generative artificial intelligence.
Wanjie YANG ; Hao FU ; Xiangfei MENG ; Changsong LI ; Ce YU ; Xinting ZHAO ; Weifeng LI ; Wei ZHAO ; Qi WU ; Zheng CHEN ; Chao CUI ; Song GAO ; Zhen WAN ; Jing HAN ; Weikang ZHAO ; Dong HAN ; Zhongzhuo JIANG ; Weirong XING ; Mou YANG ; Xuan MIAO ; Haibai SUN ; Zhiheng XING ; Junquan ZHANG ; Lixia SHI ; Li ZHANG
Chinese Critical Care Medicine 2025;37(5):477-483
The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence
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Humans
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Delivery of Health Care
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Generative Artificial Intelligence
4.Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine.
Xin-Ran DU ; Meng-Yi WU ; Mao-Can TAO ; Ying LIN ; Chao-Ying GU ; Min-Feng WU ; Yi CAO ; Da-Can CHEN ; Wei LI ; Hong-Wei WANG ; Ying WANG ; Yi WANG ; Han-Zhi LU ; Xin LIU ; Xiang-Fei SU ; Fu-Lun LI
Journal of Integrative Medicine 2025;23(6):641-653
Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy*
;
Humans
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Medicine, Chinese Traditional/methods*
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Integrative Medicine
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Drugs, Chinese Herbal/therapeutic use*
;
Practice Guidelines as Topic
5.Transforaminal interbody debridement and fusion with antibiotic-impregnated bone graft to treat pyogenic discitis and vertebral osteomyelitis: a comparative study in Asian population
Chao-Chien CHANG ; Hsiao-Kang CHANG ; Meng-Ling LU ; Adam WEGNER ; Re-Wen WU ; Tsung-Cheng YIN
Asian Spine Journal 2025;19(1):38-45
Methods:
Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups.
Results:
Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°.
Conclusions
TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.
6.Transforaminal interbody debridement and fusion with antibiotic-impregnated bone graft to treat pyogenic discitis and vertebral osteomyelitis: a comparative study in Asian population
Chao-Chien CHANG ; Hsiao-Kang CHANG ; Meng-Ling LU ; Adam WEGNER ; Re-Wen WU ; Tsung-Cheng YIN
Asian Spine Journal 2025;19(1):38-45
Methods:
Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups.
Results:
Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°.
Conclusions
TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.
7.Transforaminal interbody debridement and fusion with antibiotic-impregnated bone graft to treat pyogenic discitis and vertebral osteomyelitis: a comparative study in Asian population
Chao-Chien CHANG ; Hsiao-Kang CHANG ; Meng-Ling LU ; Adam WEGNER ; Re-Wen WU ; Tsung-Cheng YIN
Asian Spine Journal 2025;19(1):38-45
Methods:
Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups.
Results:
Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°.
Conclusions
TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.
8.Clinical and pathological characteristics of pediatric tumors with DICER1 mutations detected by Sanger sequencing
Meng ZHANG ; Xingfeng YAO ; Nan ZHANG ; Chao JIA ; Yaqian WU ; Baofeng YANG ; Shen YANG ; Lejian HE
Chinese Journal of Pathology 2025;54(12):1288-1296
Objective:To investigate the clinicopathological and molecular genetic characteristics of pediatric tumors with DICER1 mutations.Methods:A total of 90 patients diagnosed with various types of pediatric tumors at Beijing Children′s Hospital, Capital Medical University, Beijing, China from July 2023 to September 2025 were included in this study. PCR amplification and Sanger sequencing were performed to detect the coding-region mutations of the DICER1 gene. The clinical, histopathological, and molecular genetic features of the cases with DICER1 mutation were then analyzed.Results:Among the 90 patients, 39 were male and 51 were female, with an age of onset ranging from 1 month to 17 years [median 7.13 (2.77, 10.37) years]. DICER1 mutations were detected in 37 patients (37/90, 41.1%). Among them, 9 cases harbored one mutation [6 pleuropulmonary blastomas (PPBs), 2 sex cord stromal tumors (SCSTs), and 1 cystic nephroma (CN)], 27 cases carried two mutations [10 PPBs, 3 anaplastic sarcomas of the kidney (ASKs), 3 SCSTs, 3 thyroid adenoma, 2 nodular thyroid goiters, 2 thyroid follicular lesions, 2 CN, 1 embryonal rhabdomyosarcoma, and 1 case with multiple primary tumors], and 1 case exhibited three mutations (bilateral ASKs). Despite variations in the site of origin, DICER1-mutant tumors shared several morphological features. Grossly, they presented as multilocular cystic, cystic-solid to solid masses. Microscopically, they exhibited a subepithelial layer of mesenchymal cells, with focal rhabdomyoblastic/chondroid/chondrosarcomatous differentiation, as well as cellular anaplasia. Germline testing using peripheral blood in the 31 patients with DICER1 mutation confirmed germline origin in 61.3% (19/31) of them. Parental analysis ( n=12) demonstrated genetic inheritance in 8 cases, predominantly from families with tumor history. Germline variants scattered throughout DICER1 and consisted of loss-of-function mutations (nonsense, frameshift, and splice-site). Somatic mutations showed distinct clustering in exons 24 and 25 hotspots (codons 1705, 1709, 1809, 1810 and 1813), primarily missense variants. Notably, one multiple primary tumor case harbored a somatic mosaic p.E1705K mutation. Conclusions:DICER1 mutations are frequently detected in pediatric PPB, CN, SCST, ASK, nodular thyroid goiter, thyroid adenoma, and genitourinary rhabdomyosarcoma, which often represent as the index case of DICER1 syndrome. Performing DICER1 mutation testing in these patients not only facilitates tumor diagnosis and secondary cancer surveillance, but also enables the comprehensive genetic risk assessment and management for patient′s family members.
9.Establishment and application of a method for detecting Toxoplasma gondii based on recombinant polymerase amplification technology
Shao-zheng SONG ; Le-ying GU ; Ying-chao WU ; Ya-qin MENG ; Kang-ying YU ; Xiao-hua HUANG
Chinese Journal of Zoonoses 2025;41(2):107-112
To establish a method for detecting Toxoplasma gondii based on recombinant polymerase amplification(RPA)technology and apply it to clinical sample validation of pet cats.Using the 529 repeat sequence of the Toxoplasma gondii gene as the target gene sequence,primers and probes were designed,and the Rep-529 recombinant plasmid was constructed as the standard.A fluorescent RPA reaction system was established.Dilute the plasmid standard 10 times to different concentrations as the detection template for sensitivity testing;Specific testing was conducted using genomic DNA from several parasitic spe-cies,including Toxoplasma gondii,Cryptosporidium,Neosporidium,Trichinella spiralis,Giardia flagellata,Babesia bo-vis and Theileria annulata as templates;Simultaneously,fluorescence RPA and RT-PCR were used to detect 52 positive and 40 negative cats clinical samples,and the coincidence rate of the detection results of the two methods were compared and ana-lyzed.The RPA reaction system was successfully established using PTRep recombinant plasmid as the standard,ToxD-F/ToxD-R as the primer,and RepD-P as the fluorescent probe.The reaction temperature was constant at 39 ℃,the reaction time was 30 minutes,and the detection sensitivity was 1 copy/μL.There is no significant cross reaction with parasites such as Cryptosporidium,Neosporidium,Trichinella spiralis,Giardia,Babesia bovis and Theileria annulata,and the specificity is good.A total of 92 clinical fecal samples from cats were tested,and the positive coincidence rate of fluorescence RPA detection method was higher than that of conventional RT-PCR method(98.08%vs.82.69%),and the difference of the positive rate was not statistically significant(X2=1.392,P>0.05).The fluorescence RPA detection method for Toxoplasma gondii suc-cessfully established in this study has the characteristics of being fast,sensitive,specific,accurate,and reliable.It can be used as a rapid clinical detection kit for Toxoplasma gondii in cats and other animals,providing new technical support for the subsequent epidemiological monitoring and precise clinical diagnosis of toxoplasmosis in cats,other animals,and humans in the future.
10.Distribution and resistance profiles of bacterial strains isolated from cerebrospinal fluid in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Juan MA ; Lixia ZHANG ; Yang YANG ; Fupin HU ; Demei ZHU ; Han SHEN ; Wanqing ZHOU ; Wenen LIU ; Yanming LI ; Yi XIE ; Mei KANG ; Dawen GUO ; Jinying ZHAO ; Zhidong HU ; Jin LI ; Shanmei WANG ; Yafei CHU ; Yunsong YU ; Jie LIN ; Yingchun XU ; Xiaojiang ZHANG ; Jihong LI ; Bin SHAN ; Yan DU ; Ping JI ; Fengbo ZHANG ; Chao ZHUO ; Danhong SU ; Lianhua WEI ; Fengmei ZOU ; Xiaobo MA ; Yanping ZHENG ; Yuanhong XU ; Ying HUANG ; Yunzhuo CHU ; Sufei TIAN ; Hua YU ; Xiangning HUANG ; Sufang GUO ; Xuesong XU ; Chao YAN ; Fangfang HU ; Yan JIN ; Chunhong SHAO ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Fang DONG ; Zhiyong LÜ ; Lei ZHU ; Jinhua MENG ; Shuping ZHOU ; Yan ZHOU ; Chuanqing WANG ; Pan FU ; Yunjian HU ; Xiaoman AI ; Ziyong SUN ; Zhongju CHEN ; Hong ZHANG ; Chun WANG ; Yuxing NI ; Jingyong SUN ; Kaizhen WEN ; Yirong ZHANG ; Ruyi GUO ; Yan ZHU ; Jinju DUAN ; Jianbang KANG ; Xuefei HU ; Shifu WANG ; Yunsheng CHEN ; Qing MENG ; Yong ZHAO ; Ping GONG ; Ruizhong WANG ; Hua FANG ; Jilu SHEN ; Jiangshan LIU ; Hongqin GU ; Jiao FENG ; Shunhong XUE ; Bixia YU ; Wen HE ; Lin JIANG ; Longfeng LIAO ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(3):279-289
Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3%)and from outpatient and emergency care patients(4.7%).Overall,19.6%of the isolates were from children and 80.4%were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0%and 32.0%,respectively.Coagulase negative Staphylococcus accounted for 73.0%of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2%in children and 45.6%in adults.The prevalence of MRCNS was 67.6%in adults and 69.5%in children.A small number of vancomycin-resistant Enterococcus faecium(2.2%)and linezolid-resistant Enterococcus faecalis(3.1%)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2%and 76.4%in children,70.5%and 63.5%in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3%and 47.7%in children,6.4%and 47.9%in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0%and 37.1%in children,81.7%and 39.9%in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

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