1.Applications of Vaterite in Drug Loading and Controlled Release
Xiao-Hui SONG ; Ming-Yu PAN ; Jian-Feng XU ; Zheng-Yu HUANG ; Qing PAN ; Qing-Ning LI
Progress in Biochemistry and Biophysics 2025;52(1):162-181
Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.
2.Diagnostic value of multimodal MR in differentiating fibroadenoma from phyllodes tumor with maximum diameter≥5 cm
Lijia WANG ; Hui FENG ; Jiangyang PAN ; Qian XU ; Qi WANG
Journal of Practical Radiology 2024;40(3):377-380,410
Objective To analyze the clinical and MR characteristics of fibroadenoma(FA)and phyllodes tumor(PT)with maxi-mum diameter≥5 cm.Methods A total of 33 cases with FA and 34 cases with PT were selected,and all lesions with maximum diameter≥5 cm were confirmed by surgical pathology.The clinical and MR characteristics were analyzed retrospectively.Results PT and FA with tumor maximum diameter≥5 cm were more common in perimenopausal women[(47.35±11.36)years old vs(49.42±11.73)years old,P>0.05],while the FA patient was with the wider age range(19-79 years old).There was statistically significant difference in tumor maximum diameter between PT group and FA group(P<0.001),and tumor maximum diameter of PT group(median 7.06 cm,tumor maximum diameter 17.3 cm)was significantly larger than that of FA group.Coarse calcification was more common in the FA group compared to the PT group(5 vs 0,P=0.011).High signal on T1WI was more common in PT group rela-tive to FA group(50%vs 9.1%,P<0.001).There were no significant differences between the two groups in four characteristics,including tumor margin lobulation(97.1%vs 81.8%),T2WI low signal separation(32.4%vs 30.3%),fibroglandular tissue(FGT),and background parenchymal enhancement(BPE)(P>0.05).Time-signal intensity curve(TIC)of FA group showed typeⅠ and Ⅱ curves,while 4 cases(11.8%)in PT group showed type Ⅲ curves,and there was statistically significant difference in TIC between the two groups(P=0.008).The apparent diffusion coefficient(ADC)values of PT group[(1.48±0.17)×10-3mm2/s]was slightly lower than that of FA group[(1.55±0.20)×10-3 mm2/s],and there was no significant difference in ADC between the two groups(P>0.05).The receiver operating characteristic(ROC)curve showed that the best diagnostic cut-off value for distinguishing between PT and FA with maximum diameter≥5 cm was 6.36 cm,the area under the curve(AUC)was 0.927[95%confidence in-terval(CI)0.860-0.994;P<0.001].The AUC of the T1 WI high signal was 0.705,and the standard error was 0.065(95%CI 0.578-0.831;P=0.004).Conclusion Among FA and PT with tumor maximum diameter≥5 cm,PT appear to be more larger lesion and prone to higher signal intensity on T1WI compared to FA,while coarse calcification is more common in FA.
3.A retrospective analysis of the etiological characteristics and infection risks of patients critically ill with multidrug-resistant bacteria in rehabilitation wards
Huaping PAN ; Zhen WANG ; Xiaojiao ZHANG ; Jin GONG ; Jianfeng ZHAO ; Lizhi LIU ; Jiamei LIU ; Huiyue FENG ; Fang LV ; Hui FENG
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(3):205-209
Objective:To explore the microbiological and disease distribution characteristics of multidrug-resistant bacteria in patients hospitalized in a critical care rehabilitation ward, and to analyze the risk factors leading to multidrug-resistant bacterial infections.Methods:Microbiology screening data describing 679 patients admitted to a critical care rehabilitation ward were retrospectively analyzed to divide the subjects into a multidrug-resistant group (positive for multidrug-resistant bacterial infections, n=166) and a non-multidrug-resistant group (negative for multidrug-resistant bacterial infections, n=513). The risk factors were then analyzed using logistic regression. Results:Among 369 strains of multidrug-resistant bacteria observed, 329 were gram-negative bacteria (89.2%), mainly Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. They were distributed in sputum (56.9%) and mid-epidemic urine (28.2%) specimens. Patients whose primary disease was hemorrhagic or ischemic cerebrovascular disease accounted for 40.96% and 23.49% of the multidrug-resistant bacterial infections, respectively. Logistic regression analysis showed that albumin level, dependence on mechanical ventilation, central venous cannulation, or an indwelling urinary catheter or cystostomy tube were significant independent predictors of such infections.Conclusion:The multidrug-resistant bacterial infections of patients admitted to the critically ill rehabilitation unit are mainly caused by gram-negative bacteria. Their occurrence is closely related to low albumin levels and mechanical ventilation, as well as to bearing an indwelling central venous catheter, a urinary catheter or a cystostomy catheter.
4.Clinical and molecular genetic analysis of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome
Pengwu LIN ; Xuan FENG ; Shengju HAO ; Chunyang JIA ; Hairui PAN ; Chuan ZHANG ; Ling HUI ; Qinghua ZHANG
Chinese Journal of Medical Genetics 2024;41(5):612-616
Objective:To explore the genetic characteristics of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome (RTT).Methods:A male infant who was admitted to Gansu Provincial Maternity and Child Health Care Hospital in May 2020 was selected as the study subject. Clinical data of the infant was collected. Genomic DNA was extracted from peripheral blood samples from the infant and his parents, and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Result:The patient, a 4-day-old male infant, had presented with poor response, poor intake, feeding difficulties, and deceased at 8 months after birth. WES revealed that he has harbored a 0.643 Mb deletion in the 16p11.2 region, which encompassed key genes of the 16p11.2 microdeletion syndrome such as ALDOA, CORO1A, KIFF22, PRRT2 and TBX6. His father has carried the same deletion, but was phenotypically normal. The deletion was predicted to be pathogenic. The child was also found to harbor a maternally derived c. 763C>T (p.R255X) hemizygous variant of the MECP2 gene, which was also predicted to be pathogenic (PVS1+ PS4+ PM2_Supporting). Conclusion:The 16p11.2 deletion and the MECP2: c.763C>T (p.R255X) variant probably underlay the pathogenesis in this infant.
5.Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study
Ding-Hua CHEN ; Chao-Fan LI ; Yue NIU ; Li ZHANG ; Yong WANG ; Zhe FENG ; Han-Yu ZHU ; Jian-Hui ZHOU ; Zhe-Yi DONG ; Shu-Wei DUAN ; Hong WANG ; Meng-Jie HUANG ; Yuan-Da WANG ; Shuo-Yuan CONG ; Sai PAN ; Jing ZHOU ; Xue-Feng SUN ; Guang-Yan CAI ; Ping LI ; Xiang-Mei CHEN
Chinese Journal of Infection Control 2024;23(3):257-264
Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P<0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P>0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P>0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
6.GPR40 novel agonist SZZ15-11 regulates glucolipid metabolic disorders in spontaneous type 2 diabetic KKAy mice
Lei LEI ; Jia-yu ZHAI ; Tian ZHOU ; Quan LIU ; Shuai-nan LIU ; Cai-na LI ; Hui CAO ; Cun-yu FENG ; Min WU ; Lei-lei CHEN ; Li-ran LEI ; Xuan PAN ; Zhan-zhu LIU ; Yi HUAN ; Zhu-fang SHEN
Acta Pharmaceutica Sinica 2024;59(10):2782-2790
G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKAy mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKAy mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg-1) group and SZZ (100 mg·kg-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg-1 TAK875, 50 and 100 mg·kg-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured
7.Surveillance of antifungal resistance in clinical isolates of Candida spp.in East China Invasive Fungal Infection Group from 2018 to 2022
Dongjiang WANG ; Wenjuan WU ; Jian GUO ; Min ZHANG ; Huiping LIN ; Feifei WAN ; Xiaobo MA ; Yueting LI ; Jia LI ; Huiqiong JIA ; Lingbing ZENG ; Xiuhai LU ; Yan JIN ; Jinfeng CAI ; Wei LI ; Zhimin BAI ; Yongqin WU ; Hui DING ; Zhongxian LIAO ; Gen LI ; Hui ZHANG ; Hongwei MENG ; Changzi DENG ; Feng CHEN ; Na JIANG ; Jie QIN ; Guoping DONG ; Jinghua ZHANG ; Wei XI ; Haomin ZHANG ; Rong TANG ; Li LI ; Suzhen WANG ; Fen PAN ; Jing GAO ; Lu JIANG ; Hua FANG ; Zhilan LI ; Yiqun YUAN ; Guoqing WANG ; Yuanxia WANG ; Liping WANG
Chinese Journal of Infection and Chemotherapy 2024;24(4):402-409
Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33%of which were isolated from sterile body sites,mainly from blood(38.86%)and pleural effusion/ascites(10.21%).The predominant species of Candida were Candida albicans(44.51%),followed by Candida parapsilosis complex(19.46%),Candida tropicalis(13.98%),Candida glabrata(10.34%),and other Candida species(0.79%).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62%).Only 2.97%of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61%and a resistance rate of 9.42%to fluconazole,and susceptibility rates above 90%to other drugs.Candida glabrata had a SDD rate of 92.01%and a resistance rate of 7.99%to fluconazole,resistance rates of 32.27%and 48.24%to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90%to other drugs.Candida tropicalis had resistance rates of 29.55%and 26.24%to fluconazole and voriconazole,respectively,resistance rates of 76.60%and 21.99%to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36%to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.
8.Molecular mechanism of luteolin against acute lung injury based on network pharmacology and molecular docking
Xue-Feng WANG ; Xin-Zhi PAN ; Ning CAO ; Ke-Yi SUN ; Dhar RANA ; Hui-Fang TANG
Chinese Pharmacological Bulletin 2024;40(8):1583-1591
Aim To explore the molecular mechanism of luteolin against acute lung injury by network phar-macology and molecular docking technology,and to conduct experimental verification.Methods The re-lated targets of luteolin were predicted by PubChem and Swiss Target Prediction databases.Acute lung in-jury-related targets were collected through the Gene-Cards database.Venny 2.1 was used to draw the Venn diagram,and the common targets of drug and disease were obtained.The protein interaction network(PPI)was established by String online platform,and the core targets were screened by Cytoscape 3.8.2 software.The functional enrichment analysis of Gene Ontology(GO)and pathway enrichment analysis of Kyoto Ency-clopedia of Gene and Genome(KEGG)were per-formed on the common targets using the DAVID data-base,and the results were visualized.Finally,molecu-lar docking was performed by Auto Dock software,and the molecular results were visualized by Pymol.The mouse acute lung injury model was constructed.HE staining was used to detect histopathology,and Western blot was used to detect lung tissue related proteins.Results After screening,85 common targets were ob-tained.Among them,the core targets were AKT1,EG-FR,SRC,MMP9,ESR1,PTGS2,etc.GO enrichment analysis obtained 265 biological processes,including signal transduction,protein phosphorylation,and nega-tive regulation of apoptosis.There were 48 cells,main-ly including plasma membrane,cell solute,cytoplasm,etc.There are 107 molecular functions,mainly inclu-ding ATP binding,protein serine/threonine/tyrosine ki-nase activity,protein kinase activity and so on.A total of 92 signaling pathway were obtained by KEGG path-way enrichment analysis,which mainly acted on PI3 K-AKT signaling pathway,ErbB signaling pathway,VEGF signaling pathway,etc.Molecular docking results showed that luteolin had good docking activity with core targets AKT1,EGFR,SRC,MMP9,ESR1,PTGS2,MMP2,GSK3 B,KDR and PARP1.The binding ener-gy of ERS1,GSK3B and MMP2 was lower than-5.0 kal·mol-1,and the affinity with luteolin was stronger.The pathological results of lung tissue showed that lute-olin could inhibit inflammatory infiltration and had a strong anti-inflammatory effect in LPS-induced acute lung injury model in mice.Western blot experiments showed that luteolin might alleviate the inflammatory response by inhibiting the phosphorylation of AKT.Conclusions Luteolin can play an anti-acute lung in-jury role through multi-target and multi-channel mecha-nisms,which may be closely related to the inhibition of AKT phosphorylation.
9.Correlation among Serum sMICA,sMICB Levels,Autoantibody Expression and Disease Activity in Patients with Systemic Lupus Erythematosus
Tao RAN ; Feng PAN ; Yonghong WANG ; Hui PANG ; Feng WEN ; Xu CHEN ; Jiacai XIA
Journal of Modern Laboratory Medicine 2024;39(4):100-104,149
Objective To investigate the relationship among circulating soluble major histocompatibility complex class Ⅰ-related chain A(sMICA),soluble major histocompatibility complex class Ⅰ-related chain B(sMICB),the activity of systemic lupus erythematosus(SLE)and autoantibodies.Methods A total of 156 SLE patients(SLE group)and 103 healthy volunteers(control group)who underwent physical examination in outpatient physical examination center were selected from the Qianjiang Hospital Affiliated to Chongqing University from January 2020 to January 2023.According to SLE disease activity score(SLEDAI),these SLE patients were divided into mild activity group(n=43),moderate activity group(n=69),and severe activity group(n=44).Serum levels of sMICA and sMICB,and the proportion of autoantibodies and peripheral blood NK cells were detected.Spearman or Pearson method was used to analyze the correlation among sMICA,sMICB,score,autoantibodies and peripheral blood NK cells proportion.Receiver operating characteristics(ROC)curve was used to evaluate the value of sMICA and sMICB in the diagnosis of SLE activity.Results Serum sMICA(173.65±23.92 pg/ml)and sMICB(96.35±15.74 pg/ml)levels in SLE group were higher than those in control group(32.51±6.27 pg/ml,12.03±2.47 pg/ml),while the proportion of CD3-CD56+NK cells(12.02%±2.65%)in peripheral blood was lower than that in control group(18.35%±3.71%),and the differences were statistically significant(t=58.498,53.897,-16.010,all P<0.05).Serum sMICA and sMICB levels in severe active group were higher than those in moderately active group and mildly active group(t=8.192,12.352;19.652,23.742,all P<0.05),and the proportion of CD3-CD56+NK cells in peripheral blood was lower than that in moderate and mild active groups(t=8.154,10.658,P<0.05).The differences in positive rates of anti-dsDNA antibody,anti-nuclear antibody,anti-nucleosome antibody and anti-histone antibody in SLE patients with different disease activities were significant(x2=8.795,7.216,7.539,8.946,all P<0.05).Serum sMICA and sMICB levels in SLE patients were positively correlated with SLED AI score,anti-dsDNA antibody,anti-nuclear antibody,anti-nucleosome antibody and anti-histone antibody(r=0.206~0.402,all P<0.05),and negatively correlated with the proportion of CD3-CD56+NK cells in peripheral blood(r=-0.563,-0.427,all P<0.05).The areas under the curve of SLE in severe active group diagnosed by sMICA and sMICB alone were 0.652 and 0.704,respectively.The area under the curve of SLE in severe active group diagnosed by sMICA and sMICB combined with SLE was 0.812,which was higher than that by the single diagnosis(Z=3.050,2.346,all P<0.05).Conclusion The increased serum sMICA and sMICB levels in SLE patients were associated with the increased positive rate of SLE autoantibodies,the decreased proportion of NK cells in peripheral blood and the enhanced disease activity,which could be used as potential markers of SLE.
10.Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China
Rong LIU ; Zhicai YU ; Changxue XIAO ; Shufang XIAO ; Juan HE ; Yan SHI ; Yuanyuan HUA ; Jimin ZHOU ; Guoying ZHANG ; Tao WANG ; Jianyu JIANG ; Daoxue XIONG ; Yan CHEN ; Hongbo XU ; Hong YUN ; Hui SUN ; Tingting PAN ; Rui WANG ; Shuangmei ZHU ; Dong HUANG ; Yujiang LIU ; Yuhang HU ; Xinrui REN ; Mingfang SHI ; Sizun SONG ; Jumei LUO ; Juan LIU ; Juan ZHANG ; Feng XU
Chinese Journal of Pediatrics 2024;62(3):204-210
Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

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