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.Inhibitory effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure via regulation of IGF-1 expression
Li-Ying YE ; Guang-Hui PAN ; Ping ZHAO ; Ze-Peng WANG ; Cheng LIU ; Ying-Ying LI ; Fa-Rong ZHANG
Chinese Traditional Patent Medicine 2024;46(3):788-794
AIM To explore the effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure(CRF)and its mechanism.METHODS Wistar rats were randomly divided into the blank group for normal feeding and the model group for the establishment of CRF rat models by 5/6 nephrectomy.Subsequently,the successfully established rat models were randomly divided into the model group,the Heidihuang Pills group(10.43 g/kg),and the Heidihuang Pills+IGF-1R blocker(JB1)group for a regimen of 7-day subcutaneous injection of 18 μg/kg JB1 followed by gavage of 10.43 g/kg Heidihuang Pills.Eight weeks after the administration,the rats had their serum levels of Scr and BUN detected;their pathological changes of renal tissue observed by HE and Masson staining;their renal protein expressions of TGF-β,HIF-1α and α-SMA detected by immunohistochemistry;their renal protein expressions of IGF-1R and TGF-β detected by Western blot;and their renal mRNA expressions of IGF-1R and TGF-β detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed increased serum levels of Scr and BUN(P<0.05);increased,degree of renal fibrosis,and renal fibrosis area(P<0.05);increased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P<0.05);and decreased expressions of IGF-1R mRNA and protein(P<0.05).Compared with the model group,the Heidihuang Pills group displayed decreased serum Scr and BUN levels(P<0.05);decreased inflammatory cells in renal interstitium and the fibrosis degree(P<0.05);decreased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P<0.05);and increased expressions of IGF-1R mRNA and protein(P<0.05).However,the administration of JB1 could weaken the improvement effect of Heidihuang Pills on renal fibrosis in CRF rats(P<0.05).CONCLUSION Heidihuang Pills can inhibit the renal fibrosis in CRF rats,and the inhibition process is related to up-regulated IGF-1 expression and promoted combination of IGF-1 and IGF-1R.
3.Study on fatigue vibration evaluation of ultrasonic knife tip based on Q factor
Ke-Sheng WANG ; Ze-Kai LI ; Pei LIU ; Jing-Sheng SUN ; Xu-Guang PENG ; Shuang-Shuang LI ; Qian-Hong HE ; Zhen LIU
Chinese Medical Equipment Journal 2024;45(6):17-22
Objective To propose a Q factor-based fatigue vibration evaluation method of the ultrasonic knife tip.Methods Firstly,an ultrasonic cutter fatigue testing table was established to realize repeated cutting,which was composed of a power supply module,a three-axis moving module,an ultrasonic cutter clamping module and a control module.Secondly,10 ultrasonic knives of some brand underwent fatigue testing with the table,during which non-contact measurement of the ultrasonic knife tip vibration was carried out and the Q factors were calculated at the five periods of the fatigue test,including the periods before cutting,after 500 times of cutting,after 1 000 times of cutting,after 2 000 times of cutting and after 3 000 times of cutting.Finally,the average cutting speed and burst pressure for coagulated vessels were computed at each period to validata the effectiveness of the method proposed.Results It's indicated that Q factor could effectively reflect the fatigue degradation of the ultrasonic knife tip,while the average cutting speed and burst pressure for coagulated vessels were difficult to efficiently evaluate the fatigue degradation level of the ultrasonic knife tip due to the uncertainty factors in the measurement process.Conclusion The proposed Q factor-based evaluation method can directly evaluate fatigue vibration of the ultrasonic knife tip in an accurate and quantitative manner.[Chinese Medical Equipment Journal,2024,45(6):17-22]
4.Accurate quantitative evaluation of MRI scanning noise based on laser vibrometry technology
Ke-Sheng WANG ; Pei-Jia XU ; Pei LIU ; Jing-Sheng SUN ; Ze-Kai LI ; Xu-Guang PENG ; Shuang-Shuang LI ; Qian-Hong HE ; Zhen LIU
Chinese Medical Equipment Journal 2024;45(10):20-24
Objective To carry out accurate quantative evaluation of MRI scanning noise based on laser vibrometry technology.Methods Skull and spine MRI was performed with mute and conventional sequences.A laser vibrometry device was used to sample the surface vibration noise at the outer edge of the inspection hole of MRI system according to GB/T 16539-1996 Acoustics—Determination of sound power levels of noise sources using vibration velocity—Measurement for seal machinery,and the indicators of sound power level,sound pressure level and perceived noise level obtained by the three calculation methods(LPN1,LPN2 and LPN3)were analyzed with some dedicated MRI noise analysis software.Results The peak sound pressure levels for conventional and mute sequences of skull scanning were 81 and 63 dB(A),respectively,and mute sequence reduced the noise level significantly;the peak sound pressure levels for conventional and mute sequences of spine scanning were 79 and 75 dB(A),respectively,and the noise reduction level was significantly lower than that of skull scanning.Significant differences in noise reduction were not found in spine scanning sequences,while were found in skull scanning sequences.During spine and skull scanning LPN1,LPN2 and LPN3 obtained by the three calculation methods of conventional and mute sequences were all higher than the overall sound power and overall pressure levels obviously.Conclusion Mute sequence can not realize linear noise reduction for the whole frequency band,the perceived noise of the human ear during MRI scanning is related directly to the scanning sequence,and there may be some bias when only one physical indicator is involved in the noise evaluation of MRI system.[Chinese Medical Equipment Journal,2024,45(10):20-24]
5.Research progress in establishment of N-methyl-N'-nitro-N-nitroso-guanidine-induced rat model of Precancerous lesion of gastric cancer.
Yu-Ting LU ; Hua-Yi LIU ; Jia-Ju SHANG ; Yi-Jia MAO ; Guang-Ze OUYANG ; Liu YANG
China Journal of Chinese Materia Medica 2021;46(16):4089-4095
Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.
Animals
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Gastric Mucosa
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Methylnitronitrosoguanidine/toxicity*
;
Precancerous Conditions/chemically induced*
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Rats
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Stomach Neoplasms/drug therapy*
6.Expert consensus on Antiviral Oral Liquid in treatment of influenza in clinical practice.
You-Ran LU ; Qing-Quan LIU ; Guo-Zhen ZHAO ; Yi-Shan CHEN ; Li-Yun HE ; Yu-Guang WANG ; Ze-Huai WEN ; Zeng-Tao SUN ; Qin LI ; Hui-Yong ZHANG
China Journal of Chinese Materia Medica 2021;46(9):2304-2308
Antiviral Oral Liquid is modified on the basis of Baihu Decoction in Treatise on Febrility Diseases by ZHANG Zhongjing and Qingwen Baidu Yin in Qing Dynasty, with effects in clearing toxic heat, repelling dampness and cooling blood. It is widely used in clinical treatment of common colds, influenza and upper respiratory tract infection, mumps, viral conjunctivitis and hand-foot-mouth disease, with a good clinical efficacy and safety. Based on a questionnaire survey of clinicians and a systematic review of study literatures on Antiviral Oral Liquid, the international clinical practice guidelines development method was adopted to analyze the optimal available evidences and expert experiences in the "evidence-based, consensus-based and experience-based" principles. The consensus was jointly reached by more than 30 multidisciplinary experts nationwide, including clinical experts of traditional Chinese and Western medicine in the field of respiratory diseases and infectious diseases, and methodological experts. In the study, literatures were retrieved based on clinical problems in the clinical survey as well as PICO clinical problems. The GRADE system was used for the classification and evaluation of evidence, and fully combined with clinical expert experience, so as to reach expert consensus by the nominal grouping method. This expert consensus recommended or suggested indications, usage and dosage, course of treatment, intervention time for treatment, and the safety and precautions of Antiviral Oral Liquid for treatment of influenza, and can provide reference for the rational use of this drug in clinical practice.
Antiviral Agents/therapeutic use*
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Consensus
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Hand, Foot and Mouth Disease
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Humans
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Influenza, Human/drug therapy*
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Medicine, Chinese Traditional
7.Comparison on efficacy between fascia-oriented versus vascular-oriented lateral lymph node dissection in patients with rectal cancer.
Zhi Jie WANG ; Zheng LIU ; Jian Wei LIANG ; Ming Guang ZHANG ; Shi Wen MEI ; Hai Yu SHEN ; Jia Nan CHEN ; Juan LI ; Fu Qiang ZHAO ; Fang Ze WEI ; Ti Xian XIAO ; Qian LIU
Chinese Journal of Gastrointestinal Surgery 2021;24(7):611-618
Objective: To compare the postoperative function, the short-term and long-term outcomes between fascia-oriented and vascular-oriented lateral lymph node dissection (LLND) in patients with rectal cancer. Methods: A retrospective cohort study was performed. Clinical data of patients who received total mesorectal excision (TME) with LLND at National Cancer Center, Cancer Hospital of Chinese Academy of Medical Science from January 2014 to December 2019 were retrospectively collected. Inclusion criteria were as follows: (1) rectal cancer was pathologically diagnosed, and the lower margin was below the peritoneal reflection. (2) resectable advanced rectal cancer with suspected lateral lymph node metastasis was evaluated based on rectal MRI assessment. (3) preoperative MRI showed lateral lymph node short diameter ≥5 mm and/or lymph node morphology (spike, blur, irregular) as well as heterogenous signal intensity. Lymph node shrinkage was less than 60% after receiving neoadjuvant therapy based on the reassessment of rectal MRI. (4) TME+LLND surgery was performed synchronously. Exclusion criteria were as follows: (1) previous history of pelvic surgery; (2) preoperative cystitis, urethritis, moderate and severe prostatic hyperplasia and other diseases resulting in abnormal urination function; (3) preoperative sexual dysfunction or loss of function; (4) patients receiving LLND due to lateral recurrence after TME; (5) distant metastasis of the tumor at initial diagnosis; (6) Incomplete collection of clinical data. A total of 73 consecutive patients were enrolled in this study. Based on the surgical approaches in performing LLND, patients were divided into fascia-oriented group (n=30) and vascular-oriented group (n=43). There were no significant differences in baseline data between the two groups (all P>0.05). The main outcome indicators of this study were the incidence of postoperative urinary and male sexual dysfunction, the efficacy, the number of lateral lymph nodes harvested and the detection rate of positive lymph nodes. Overall survival (OS) rates and progression free survival (PFS) rates were calculated by the Kaplan-Meier method and compared by log-rank test. Results: All patients in both groups completed surgery successfully. There were no significant differences in operation time, intraoperative blood loss, postoperative complications, and the length of hospital stay between the two groups (all P>0.05). In the whole group, the incidence of postoperative urinary dysfunction and male sexual dysfunction was 43.8% (32/73) and 62.5% (25/40), respectively. The median number of lateral lymph nodes harvested was 8.0(4.0,11.0) with a positive rate of 20.5%(15/73). Compared to the vascular-oriented group, the fascia-oriented group demonstrated a decreased rate of urinary dysfunction [26.7% (8/30) vs. 55.8% (24/43), χ(2)=6.098, P=0.014], lower rate of sexual dysfunction in males [6/15 vs. 76% (19/25), χ(2)=5.184, P=0.023], more harvested lateral lymph nodes [M (P25, P75): 9.5 (6.8, 15.3) vs. 6.0 (3.0, 9.0), Z=-2.849, P=0.004]. There was no significant difference in the positvie rate of lateral lymph nodes between the two groups [20% (6/30) versus 20.9% (9/43), χ(2)=0.009, P=0.923]. Three(4.1%) patients were lost during a median follow-up of 34 (1-66) months. The 3-year PFS and OS of the whole cohort were 69.5% and 88.3%, respectively. No significant difference in 3-year PFS rates (79.6% vs. 62.0%, P=0.172) and 3-year OS rates (91.2% vs. 85.9%, P=0.333) were observed between the fascia-oriented group and the vascular-oriented group (both P>0.05). Conclusion: Fascia-oriented LLND is associated with lower risk of postoperative urinary and male sexual dysfunction in patients with rectal carcinoma, and harvest of more lymph nodes, but no significant advantage in long-term survival.
Fascia
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Humans
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Lymph Node Excision
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Lymph Nodes
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Male
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Neoplasm Recurrence, Local
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Rectal Neoplasms/surgery*
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Retrospective Studies
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Treatment Outcome
8.Virtual screen of effective AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking.
Guang-Xin LIU ; Ze-Feng ZHAO ; Jing XIE ; Jie SANG ; Ye-Fei LIANG ; Ming-Cheng QIAN ; Cui-Qin LI
China Journal of Chinese Materia Medica 2020;45(10):2431-2438
This research is to predict anti-Alzheimer's disease active constituents on the target of acetylcholinesterase(AChE) from Glycyrrhizae Radix et Rhizoma with the help of pharmacophore and molecular docking. AChE ligand-based pharmacophore model was set up and the molecular library of the constituents from Glycyrrhizae Radix et Rhizoma were established by collecting literature. Then the constituents from Glycyrrhizae Radix et Rhizoma were screen for the potential AChE inhibitory potency in silico through matching with the best pharmacophore model. The flexible docking was used to evaluate the interactions between compounds screened from pharmacophore model and AChE protein(PDB ID:4 EY7). The interactions were expressed including but not limited to CDOCKER interaction energy, hydrogen bonds and non-bonding interactions. The molecular library of Glycyrrhizae Radix et Rhizoma contains 44 chemical constituents. As for the pharmacophore model, six kinds of potential AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma were considered to be the promising compounds according to the results of searching 3 D database of pharmacophore model. The molecular docking was possessed and the interaction patterns were given to show the detail interactions. The compounds screening from the pharmacophore model were consistent with the existing studies to some degree, indicating that the virtual screen protocols of AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking was reliable.
Drugs, Chinese Herbal
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Glycyrrhiza
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Molecular Docking Simulation
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Rhizome
;
Triterpenes
9. Diagnostic value of water swallow test and simple two-step swallowing provocation test for aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)
Ni LIU ; Ze-guang ZHENG ; You-xia LI ; Jie-ying HU ; Li-hong ZHONG ; Yao-yao FAN ; Rong-chan CHEN
Chinese Journal of Practical Internal Medicine 2019;39(10):904-908
OBJECTIVE: To explore the value of water swallow test(WST)and simple two-step swallowing provocation test(SSPT)in the diagnosis of aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease. METHODS:87 hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease were recruited from the First Affiliated Hospital of Guangzhou Medical University during the period between December 2014 to December 2015. RESULTS: The number of patients of grade1,2,3,4 and 5 of water swallow test successively were 44,39,4,0 and 0. Patients with positive aspiration by the first-step(water injection of 0.4 mL)and the second-step(water injection of 2.0 m L)were 16 and 0. Patients with positive aspiration by radionuclide imaging was 35. Comparison of radionuclide imaging, the rate of missed diagnosis applying water swallow test was high 37.3%(31/83). Both the water swallow test and simple two-step swallowing provocation test have poor consistency with radionuclide imaging in the diagnosis of aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(McNemar consistency test P=0.00).CONCLUSION: There is a high rate of missed diagnosis applying water swallow test and simple two-step swallowing provocation test to diagnosis aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and combined use of multiple assessment methods can reduce the missed diagnosis rate of aspiration.
10.Levels of lymphocyte subsets, immunoglobulins, and complement C3 and C4 in children with hand-foot-mouth disease.
Xiao-Mei LIU ; Zhen-Ze CUI ; Shu-Jun JING ; Guang YANG
Chinese Journal of Contemporary Pediatrics 2019;21(12):1203-1207
OBJECTIVE:
To study the clinical value of lymphocyte subsets, immunoglobulins, and complement C3 and C4 in the evaluation of immune status in children with hand-foot-mouth disease (HFMD).
METHODS:
A total of 282 children with HFMD were enrolled as the HFMD group, and 130 healthy children were enrolled as the healthy control group. The percentages of peripheral CD3, CD4, and CD8 T lymphocytes, CD19 B lymphocytes, and CD56 natural killer cells were measured. The CD4/CD8 ratio was calculated. The levels of immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), and complement C3 and C4 were measured.
RESULTS:
The multivariate analysis showed that compared with the healthy control group, the HFMD group had significantly lower percentages of CD3, CD4, and CD8 T lymphocytes and levels of complement C3 and C4 (P<0.05), as well as significantly higher percentage of CD56 natural killer cells and level of IgG (P<0.05). The individual effect analysis showed that the children aged 0-3 years in the HFMD group had a significantly higher CD4/CD8 ratio than the healthy control group (P<0.05); boys aged 0-3 and ≥3 years in the HFMD group had a significantly higher level of IgM than the healthy control group (P<0.05); boys aged ≥3 years and girls aged 0-3 years in the HFMD group had a significantly lower level of IgA than the healthy control group (P<0.05).
CONCLUSIONS
Cellular and humoral immunity disorders are observed in children with HFMD. The monitoring of lymphocyte subsets and immunoglobulin levels can provide a laboratory basis for immune status assessment in children with HFMD.
Child, Preschool
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Complement C3
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Complement C4
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Female
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Hand, Foot and Mouth Disease
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Humans
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Immunoglobulins
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Infant
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Infant, Newborn
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Killer Cells, Natural
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Lymphocyte Count
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Lymphocyte Subsets
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Male

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