1.Nanomaterial-based Therapeutics for Biofilm-generated Bacterial Infections
Zhuo-Jun HE ; Yu-Ying CHEN ; Yang ZHOU ; Gui-Qin DAI ; De-Liang LIU ; Meng-De LIU ; Jian-Hui GAO ; Ze CHEN ; Jia-Yu DENG ; Guang-Yan LIANG ; Li WEI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2024;51(7):1604-1617
Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.
2.Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles.
Zhan Yi ZHANG ; Fan ZHANG ; Ye YAN ; Cai Guang CAO ; Chang Jian LI ; Shao Hui DENG ; Yue Hao SUN ; Tian Liang HUANG ; Yun He GUAN ; Nan LI ; Min LU ; Zhen Hua HU ; Shu Dong ZHANG
Journal of Peking University(Health Sciences) 2023;55(5):843-850
OBJECTIVE:
To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats.
METHODS:
A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures.
RESULTS:
Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion.
CONCLUSION
The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.
Male
;
Rats
;
Animals
;
Prostate/diagnostic imaging*
;
Paraffin
;
Indocyanine Green
;
Rats, Sprague-Dawley
;
Fluorescent Dyes
3.Clinical and genetic analyses of Joubert syndrome in children.
Guang-Yu ZHANG ; Yun-Xia ZHAO ; Hui-Ling ZHAO ; Guo-Hao TANG ; Peng-Liang WANG ; Deng-Na ZHU
Chinese Journal of Contemporary Pediatrics 2023;25(5):497-501
OBJECTIVES:
To study the clinical and genetic features of Joubert syndrome (JS) in children.
METHODS:
A retrospective analysis was performed on the clinical data, genetic data, and follow-up data of 20 children who were diagnosed with JS in the Department of Children's Rehabilitation, the Third Affiliated Hospital of Zhengzhou University, from January 2017 to July 2022.
RESULTS:
Among the 20 children with JS, there were 11 boys and 9 girls. The common clinical manifestations were developmental delay (20 children, 100%), abnormal eye movement (19 children, 95%), and hypotonia (16 children, 80%), followed by abnormal respiratory rhythm in 5 children (25%) and unusual facies (including prominent forehead, low-set ears, and triangular mouth) in 3 children (15%), and no limb deformity was observed. All 20 children (100%) had the typical "molar tooth sign" and "midline cleft syndrome" on head images, and 6 children (30%) had abnormal eye examination results. Genetic testing was performed on 7 children and revealed 6 pathogenic genes, i.e., the CPLANE1, RPGRIP1L, MKS1, CC2D2A, CEP120, and AHI1 genes.
CONCLUSIONS
For children with developmental delay, especially those with abnormal eye movement and hypotonia, it is recommended to perform a head imaging examination to determine the presence or absence of "molar tooth sign" and "midline cleft syndrome", so as to screen for JS to avoid missed diagnosis and misdiagnosis. There are many pathogenic genes for JS, and whole-exome sequencing can assist in the diagnosis of JS.
Male
;
Female
;
Humans
;
Child
;
Cerebellum
;
Abnormalities, Multiple/genetics*
;
Kidney Diseases, Cystic/genetics*
;
Eye Abnormalities/genetics*
;
Retina
;
Retrospective Studies
;
Muscle Hypotonia/genetics*
4.Interpretation of the clinical guideline for point-of-care ultrasonography in the neonatal intensive care unit in the United States.
Wen-Hui DONG ; Bo-Yin DENG ; Guang YUE ; Yasser ELSAYED ; Rong JU ; Jian-Hui WANG ; Yuan SHI
Chinese Journal of Contemporary Pediatrics 2023;25(7):672-677
In December 2022, the American Academy of Pediatrics released a clinical guideline for point-of-care ultrasonography (POCUS) in the neonatal intensive care unit (NICU). The guideline outlined the development and current status of POCUS in the NICU, and summarized the key elements and implementation guidelines for successful implementation of POCUS in the NICU. This article provides an overview of the key points of the clinical guideline and analyzes the current status of POCUS in China, providing a reference for the implementation of POCUS in neonatal care in China.
Infant, Newborn
;
Humans
;
United States
;
Child
;
Intensive Care Units, Neonatal
;
Point-of-Care Systems
;
Ultrasonography
;
China
5.Main Infection Control Measures for Respiratory Infectious Diseases in Medical Institutions and Public Places in China.
Le-le DENG ; Gui-Lian LI ; Tao CHEN ; Ya-Jun HAN ; Jin-Long WANG ; Hui ZHANG ; Jun CHENG ; Guang-Xue HE
Acta Academiae Medicinae Sinicae 2023;45(2):171-177
Respiratory infectious diseases (RID) are the major public health problems threatening the people's lives and health.Infection control (IC) is one of the effective tools to contain the occurrence and spread of RID.We collected the articles and data on IC published since January 1,2018 and summarized the achievements,problems,and challenges of IC from administrative control,management control,environment and engineering control,and personal protection in the medical institutions and public places in China.The efforts for IC vary in different regions and medical institutions of different levels.There are still links to be improved for IC from administrative control,management control,environment and engineering control,and personal protection,especially in community-level medical institutions and public areas.It is urgent to strengthen the implementation of IC policies and conduct IC precisely according to local situations.We proposed the following suggestions.First,the existing IC products and tools should be applied to precisely implement the IC measures;second,modern high technology should be employed to develop efficient and convenient IC products and tools;finally,a digital or intelligent IC platform should be built for monitoring infections,so as to contain the occurrence and spread of RID.
Humans
;
COVID-19
;
Infection Control
;
Communicable Diseases
;
China/epidemiology*
6.Prevalence and risk factors of Giardia lamblia infections among colorectal cancer patients in Henan Province
Hui-hui CHEN ; Yan DENG ; Zhi LI ; Zhen-lei WANG ; Zeng-ci RUN ; Ting ZHANG ; Yu-chun CAI ; Hong-wei ZHANG ; Zhu-hua HU ; Jun-hu CHEN ; Li-guang TIAN ; Jian LI
Chinese Journal of Schistosomiasis Control 2022;34(4):370-377
Objective To investigate the epidemiological characteristics and identify the risk factors of Giardia lamblia infections among patients with colorectal cancer in Henan Province. Methods A cross-sectional study was performed for questionnaire surveys among colorectal cancer patients in Henan Cancer Hospital during the period from March to July, 2021. Patients’ stool samples were collected, and the triosephosphate isomerase (tpi) gene of G. lamblia was amplified in stool samples using nested PCR assay to characterize the parasite genotype. Univariate analysis and multivariate logistic regression analyses were employed to identify the risk factors of G. lamblia infections among colorectal cancer patients. Results A total of 307 colorectal cancer patients were investigated, including 176 males (57.3%) and 131 females (42.7%). PCR assay detected 8.1% [95% confidential interval (CI): (0.056, 0.117)] prevalence of G. lamblia infections among the study subjects, and there was no significant difference in the prevalence between men [9.1%, 95% CI: (0.057, 0.143)] and women [6.9%, 95% CI: (0.037, 0.125)] (χ2 = 0.495, P = 0.482). In addition, there was no age-specific prevalence of G. lamblia infections among the participants (χ2 = 1.534, P = 0.675). Multivariate logistic regression analysis identified use of septic tanks [odds ratio (OR) = 3.336, 95% CI: (1.201, 9.267)], daily use of well water [OR = 3.042, 95% CI: (1.093, 8.465)] and raising livestock [OR = 3.740, 95% CI: (1.154, 12.121)] as risk factors of G. lamblia infections among colorectal cancer patients, and the prevalence of abdominal pain was significantly greater in colorectal cancer patients with G. lamblia infections than in those without infections (P = 0.017). Among the 25 patients with G. lamblia infections, assemblage A was characterized in 24 (96.0%) cases and assemblage B in one case (4.0%). Conclusions The prevalence of G. lamblia is high among colorectal cancer patients in Henan Province, and assemblage A is the dominant genotype of G. lamblia. Use of septic tanks, daily use of well water and raising livestock are risk factors of G. lamblia infections among patients with colorectal cancer.
7. Dihydromyricetin down-regulating the expression of nod-like receptor protein-3 in the brain tissue of ischemic stroke in rats
Hui-Ru DING ; Xin-Wei DENG ; Huai-Cun LIU ; Quan-Cheng CHENG ; Xuan FANG ; Chun-Hua CHEN ; Wei-Guang ZHANG ; Guo-Liang ZHANG
Acta Anatomica Sinica 2022;53(2):137-143
[Abstract] Objective To investigate the role of dihydromyricetin (DHM) in the treatment of ischemic stroke in rats, and to explore the effect of DHM on the expression of inflammasome. Methods The middle cerebral artery occlusion (MCAO) model was induced by endovascular suture method. The therapeutic effect and mechanism of DHM were investigated by Longa score, TTC staining, Nissl staining, immunohistochemical staining and Western bloting. Results After DHM treatment, the motor capacity of MCAO rats was significantly improved, the infarct volume was significantly reduced, the brain structure and neuron morphology were improved, and the expressions of nod-like receptor protein-3 (NLRP3) and interleukin-1(IL-1) decreased significantly. Conclusion DHM can down-regulate the expression of NLRP3 and thus reduces the cerebral infarction volume and improves neurobehavioral performance in MCAO rats.
8.TRAF6 promotes Bacillus Calmette-Guérin-induced macrophage apoptosis through the intrinsic apoptosis pathway.
Qin Mei MA ; Li LIU ; Jia Lin YU ; Zhao Qian GONG ; Xiao Ping WANG ; Xiao Ling WU ; Guang Cun DENG
Journal of Southern Medical University 2022;42(9):1279-1287
OBJECTIVE:
To investigate the role of tumor necrosis factor receptor-associated factor 6 (TRAF6) in regulating Bacillus Calmette-Guérin (BCG)-induced macrophage apoptosis.
METHODS:
The expression of TRAF6 in peripheral blood samples of 50 patients with active tuberculosis (TB) and 50 healthy individuals were detected using quantitative real-time PCR (qPCR). RAW264.7 macrophages were infected with BCG at different MOI and for different lengths of time, and the changes in expressions of Caspase 3 and TRAF6 were detected with Western blotting and qPCR. In a RAW264.7 cell model of BCG infection with TRAF6 knockdown established using RNA interference technique, the bacterial load was measured and cell apoptotic rate and mitochondrial membrane potential (MMP) were determined with flow cytometry. The expression levels of TRAF6, Caspase 3, PARP, BAX and Bcl-2 in the cells were detected using Western blotting, and the expressions of TRAF6 and Caspase 3 were also examined with immunofluorescence assay.
RESULTS:
The expression of TRAF6 was significantly upregulated in the peripheral blood of patients with active TB as compared with healthy subjects (P < 0.001). In RAW264.7 cells, BCG infection significantly increased the expressions of Caspase 3 and TRAF6, which were the highest in cells infected for 18 h and at the MOI of 15. TRAF6 knockdown caused a significant increase of bacterial load in BCG-infected macrophages (P=0.05), lowered the cell apoptotic rate (P < 0.001) and reduced the expressions of Caspase 3 (P=0.002) and PARP (P < 0.001). BCG-infected RAW264.7 cells showed a significantly increased MMP (P < 0.001), which was lowered by TRAF6 knockdown (P < 0.001); the cells with both TRAF6 knockdown and BCG infection showed a lowered BAX expression (P=0.005) and an increased expression of Bcl-2 (P=0.04).
CONCLUSION
TRAF6 promotes BCG-induced macrophage apoptosis by regulating the intrinsic apoptosis pathway.
Apoptosis
;
BCG Vaccine
;
Caspase 3/metabolism*
;
Humans
;
Intracellular Signaling Peptides and Proteins
;
Macrophages
;
Mycobacterium bovis/metabolism*
;
Poly(ADP-ribose) Polymerase Inhibitors
;
TNF Receptor-Associated Factor 6/metabolism*
;
bcl-2-Associated X Protein/metabolism*
9.Expert consensus on the strategy and measures to interrupt the transmission of schistosomiasis in China
Shan LÜ ; Chao LÜ ; Yin-Long LI ; Jing XU ; Qing-Biao HONG ; Jie ZHOU ; Jian-Feng ZHANG ; Li-Yong WEN ; Jian-Feng ZHANG ; Shing-Qing ZHANG ; Dan-Dan LIN ; Jian-Bing LIU ; Guang-Hui REN ; Yi DONG ; Yang LIU ; Kun YANG ; Zhi-Hua JIANG ; Zhuo-Hui DENG ; Yan-Jun JIN ; Han-Guo XIE ; Yi-Biao ZHOU ; Tian-Ping WANG ; Yi-Wen LIU ; Hong-Qing ZHU ; Chun-Li CAO ; Shi-Zhu LI ; Xiao-Nong ZHOU
Chinese Journal of Schistosomiasis Control 2021;33(1):10-14
Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.
10.Early incision, decompression and screw fixation for the treatment of Lisfranc injuries with foot osteofascial compartment syndrome.
Jin-Qi SONG ; Xia-Hui OUYANG ; Guang-Yuan LU ; Ding-Gen HUANG ; Xue-Bing WANG ; Xuefeng DENG
China Journal of Orthopaedics and Traumatology 2021;34(5):471-475
OBJECTIVE:
To explore clinical effect of early incision and decompression combined with screw fixation in treating Lisfranc injury and foot osteofascial compartment syndrome.
METHODS:
Clinical data of 5 patients with Lisfranc injury and foot osteofascial compartment syndrome were retrospective analysized from January 2017 to December 2018, including 4 males and 1 female, aged from 19 to 62 years old. All patients were suffered from closed injuries. The time from injury to treatment ranged from 1 to 14 h. According to Myerson classification, 1 patient was type A, 1 patient was type B, and 3 patients were type C. All patients were performed early incision decompression and screw fixation. Maryland foot functional scoring standard at 12 months after opertaion was used to evaluate clinical effect.
RESULTS:
All patients were followed up for 10 to 48 months. All fractures were achieved bone union, and healing time ranged from 3 to 9 months. All metatarsal and tarsal joints were reached to anatomical reduction. No infection, osteomyelitis, loosening or breaking of internal fixation occurred. Postopertaive Maryland foot function score at 12 months was from 44 to 97, and 2 patients got excellent result, 2 good, and 1 poor.
CONCLUSION
Early incision and decompression with screw fixation for the treatment of Lisfranc injury and foot osteofascial compartment syndrome, which has advantages of simple opertaion, thoroughly decompression, screw fixation does not occupy space, stable decompression and fixation, and could receive satisfied clinical effect.
Adult
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Bone Screws
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Compartment Syndromes/surgery*
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Decompression
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Female
;
Foot Injuries
;
Fracture Fixation, Internal
;
Fractures, Bone/surgery*
;
Humans
;
Male
;
Middle Aged
;
Retrospective Studies
;
Tarsal Joints
;
Treatment Outcome
;
Young Adult

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