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.Protective effects and mechanism of carvedilol on diabetic kidney disease in mice
Wei-Feng WU ; Ying CAO ; Hao-Jian FENG ; Cai-Neng WU ; Ping-Zheng ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(12):1799-1802
Objective To observe the effects of carvedilol on renal function in mice with diabetic kidney disease(DKD)and to preliminarily study its mechanism of action.Methods C57BL/6J male mice were randomly divided into control group,model group and experimental group,with 10 mice in each group.The mouse model of type Ⅰ diabetes was established by intraperitoneal injection of 150 mg·kg-1 streptozotocin(STZ).After successful modeling,the experimental group mice were given 10 mg·kg-1·d-1 carvedilol by gavage,while the control group and model group were given equal amounts of 0.9%NaCl.During the experiment,the fasting blood glucose(FBG)of mice were monitored weekly.After 8 weeks of administration,the urinary albumin to creatinine ratio(UACR),uric acid(UA),and other contents in the urine of mice were detected,as well as the levels of iron(Fe),superoxide dismutase(SOD),and malondialdehyde(MDA)in the renal tissue.And hematoxylin-eosin(HE)and Masson staining were performed on the renal tissue to observe the pathological changes of the kidney.Results After 8 weeks of administration,the UACR of the control group,model group and experimental group were(12.43±1.13),(63.01±20.78)and(19.79±1.94)mg·mmol-1;the UA levels were(132.10±10.14),(174.40±7.06)and(135.00±3.95)μmol·L-1;the Fe levels were(7.49±0.81),(9.98±0.46)and(7.02±0.60)μmol·g prot-1;the SOD activities were(34.56±0.58),(30.27±1.22)and(34.43±1.36)U·mg prot1;the MDA contents were(5.49±0.31),(7.72±0.17)and(4.46±0.32)nmol·mg prot-1.The differences between model group and normal group were statistically significant(all P<0.05);compared between experimental group and model group,the difference were significant(all P<0.05).Conclusion Carvedilol can alleviate the damage of renal function in diabetes mice,and its mechanism may be related to inhibiting iron death and alleviating oxidative stress injury.
3.Correlation between IL-17 gene polymorphism and type 2 diabetes mellitus in Han population in southeast Shanxi Province
Yan LI ; Qi WANG ; Lu ZHENG ; Lihui FENG ; Li MA ; Jian WEI ; Liangshu LIU
The Journal of Practical Medicine 2024;40(5):695-701
Objective To determine the correlation between single-nucleotide polymorphisms of IL-17 with type 2 diabetes in Han population in southeastern Shanxi Provincein.Methods The basic information and related clinical data of the subjects were collected of normal healthy controls and T2DM.Whole blood DNA was extracted,and IL-17 polymorphisms(rs2275913,rs3819024,rs4711998 and rs8193036)were analyzed by using a polymerase chain reaction-high temperature ligase reaction.Results There was no significant difference in the genotype and allele frequency distribution of the four SNP loci of IL-17 gene between the two groups(P>0.05).IL-17 polymorphism was not linked with T2DM in multiple genetic models after controlling for age,BMI,WC,and dyslipidemia(P>0.05).Further analysis showed that the levels of AA genotype was substantially lower of FPG and HOMA-IR levels when compared with the AG and GG genotypes,and the differences among the three groups were statistically significant(P<0.05).However,BMI,FINS,HbA1c and HOMA-βwas no statistical significance among the three groups(P>0.05).Besides,WC and HOMA-IR of AA genotype(rs3819024)were notable higher than those of GG genotype in T2DM group(P<0.05).Conclusions The IL-17 gene polymorphisms rs2275913,rs3819024,rs4711998,and rs8193036 in the Han population of southeast Shanxi Province may not be associated with T2DM.In this region Han T2DM patients,AA genotype at rs2275913 of the IL-17 gene is associ-ated to FPG and HOMA-IR,while GG genotype at rs3819024 is related to WC and HOMA-IR,which could be the potential genotype of IL-17 impacting glucose metabolism.
4.Effects of three rehydration methods on prevention of on-site and delayed blood donation-related vasovagal responses: a cluster-randomized trial
Guiyun XIE ; Shijie LI ; Jian OUYANG ; Fanfan FENG ; Xiaoxiao ZHENG ; Zhiyu ZHOU ; Lianfang MAI ; Jinyan CHEN
Chinese Journal of Blood Transfusion 2024;37(1):43-50
【Objective】 To compare the effects of 3 rehydration methods before blood donation on the prevention of on-site and delayed blood donation-related vasovagal response (VVR) . 【Methods】 From January to June 2021, 6 250 whole blood donors in 6 fixed blood donation sites signed informed consent and were divided into 198 clusters according to donor sites and dates, then they were randomly assigned to receive either oral rehydration salts (ORS), sugar water, or water group, and each drank 500 mL of ORS, sugar water or water within 20 minutes before blood donation. The researchers recorded the actual intervention accepted on site, and recorded the immediate VVR and related information. At rest after blood donation, donors submitted an electronic questionnaire containing socio-demographic information. At 48 hours after blood donation, the researchers called back every donor to record delayed VVR and related information. Logistic regression based on intention to treat (ITT) was used to analyze the difference of the incidence of VVR among the three groups, and the average treatment effect on treated (ATT) was calculated. PASS 2021was used to estimate the sample size and R (4.2.0) for statistical analysis. 【Results】 The cumulative incidence of blood donation-related VVR was 2.67% (2.29%-3.11%) among street whole blood donors under the 3 rehydration methods, in which, the incidence of immediate and delayed VVR was 1.02% (0.79%-1.31%) and 1.65% (1.36%-2.01%) respectively. ITT analysis found that ORS were more effective than water in reducing the incidence of delayed VVR【OR=0.59,95% CI[0.37,0.94]】.There was no significant difference in the incidence of immediate VVR between any two groups (P > 0.05), and there was no significant difference in the incidence of delayed VVR in the sugar water group compared with the water group (P > 0.05). There was a difference of -0.013 (【95% CI[-0.022, -0.004]】or -0.008【95% CI[-0.017, -0.000]】in the incidence of delayed VVR in the ORS group compared with water group or sugar water group, the difference was significant (P<0.05). The cumulative VVR of the three groups showed similar results to the delayed VVR. 【Conclusion】 Drinking ORS before blood donation is the most effective rehydration method to prevent delayed VVR. The next step is to establish the predictive model of delayed VVR to screen the susceptible population and provide them with ORS before blood donation, while other population can choose any liquid they like, thus achieving personalized blood donation-related VVR prevention and control.
5.DNA Polymerase θ: a Multifunctional and Error-prone DNA End Repair Enzyme
Yao WANG ; Guo-Jiang CHEN ; Jian-Nan FENG ; Yan-Chun SHI ; Jing WANG ; Yuan-Qiang ZHENG
Progress in Biochemistry and Biophysics 2024;51(3):493-503
DNA polymerase theta (Polθ), also known as DNA polymerase θ, is the member of the DNA polymerase A family and plays a crucial role in the repair of DNA double-strand breaks (DSB). Polθ has 3 distinct structural domains: the N-terminal helicase-like domain with a conserved sequence, the C-terminal polymerase domain, and the central domain, which is a disordered sequence connecting these two regions. Notably, Polθ is the only known polymerase in eukaryotes that possesses helicase activity. However, it is also an error-prone polymerase. When DNA DSBs occur, a specialized network consisting of at least 4 pathways, including classical-non homologous end joining (C-NHEJ), homologous recombination (HR), single-strand annealing (SSA), and alternative-end joining (Alt-EJ), is responsible for repairing DNA damage caused by DSBs. In the absence of major DNA repair pathways like HR, cells rely on Alt-EJ pathway mediated by Polθ to repair damaged DNA and maintain genomic stability. Nevertheless, due to the low fidelity of Polθ, Alt-EJ repair often leads to errors. Depletion of Polθ has shown to increases DSB formation and compromise genomic stability. Conversely, overexpression of Polθ has been associated with increases DNA damage markers and impairs cell cycle progression. As a result, the impact of Polθ on genome stability remains controversial. Furthermore, overexpression of Polθ is frequently observed in cancer and is associated with a characteristic mutational signature and poor prognosis. Depleting Polθ in an HR-deficient background has been shown to impair cell viability, suggesting a synthetic lethal (SL) relationship between Polθ and HR factors. In recent years, targeted chemotherapy drugs that inhibit tumor growth have gained significant attention. However, off-target effects and drug resistance pose challenges for clinical application, particularly with poly-ADP-ribose polymerase inhibitor (PARPi). Blocking Polθ activity in HR-deficient tumor cells has been found to reverse PARPi resistance, making Polθ a very promising therapeutic target in cancer treatment. The availability of crystal structures for both helicase and polymerase domain has facilitated the design of potent inhibitors of Polθ. Currently, several highly specific and effective small molecule inhibitors targeting Polθ, such as Novobiocin, RP-6685, and ART558, have been reported to effectively block various cancers with HR deficiency. The initial success of these inhibitors points to new directions for treating BRCA1/2-mutated tumors. Additionally, reducing the Alt-EJ repair pathway mediated by Polθ can improve HR repair efficiency and increase the chance of exogenous gene target integration (TI), suggesting potential new applications for Polθ inhibitors. This article reviews the recent research progress on the molecular function of Polθ and its involvement in the Alt-EJ pathway modification mechanism, providing insights for a deeper understanding of this field.
6.Progress of transcatheter aortic valve replacement in 2023
Mo-Yang WANG ; Zheng ZHOU ; Guan-Nan NIU ; Yang CHEN ; De-Jing FENG ; Xiang-Ming HU ; Wen-Ce SHI ; Yong-Jian WU
Chinese Journal of Interventional Cardiology 2024;32(1):14-19
Transcatheter aortic valve replacement(TAVR)has become one of the effective methods for treating patients with aortic valve disease.With the continuous maturity of technology,innovation of instruments and increasing experience,the indications for TAVR has been expanded.Following international trends,the number of TAVR in China has steadily increased with each passing year.In 2023,the long-term follow-up results of TAVR in low-risk AS patients further confirm the long-term benefits of TAVR.The relevant research on TAVR for patients with aortic regurgitation and patients with bicuspid aortic stenosis provide evidence support for the expansion of TAVR indications.At the same time,the development of valve devices and new technological innovations are emerging in an endless stream,and the new concept of full life cycle management is increasingly being valued.Especially in China,the development of local devices is progressing rapidly,and multiple devices have entered the clinical research stage.The clinical manifestations and research results are worth pursuing.
7.Screening and identification of human monoclonal antibodies against low-calcium response V antigen of Yersinia pestis
Li ZHANG ; Bin-Yang ZHENG ; Qi ZHANG ; Hai-Lian WU ; Hong-Xin PAN ; Feng-Cai ZHU ; Hai-Sheng WU ; Jian-Fang ZHOU
Chinese Journal of Zoonoses 2024;40(1):15-20
To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.
8.Study on the toxicity characteristics of a clinical bloodstream isolate of Salmonella Telelkebir
En-Hui ZHENG ; Yu-Feng QIU ; Jian-Hui CHEN ; Ya-Dong GAO ; Meng-Ying HUANG ; Qu-Wen LI ; Jie LIN ; Shun-Tai WENG
Chinese Journal of Zoonoses 2024;40(1):31-39
The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.
9.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
10.Predictive value of early thyroid function changes for the curative effect of 131I therapy in patients with Graves′ disease
Yan WANG ; Feng YU ; Renfei WANG ; Zhaowei MENG ; Guizhi ZHANG ; Ruiguo ZHANG ; Danyang SUN ; Xuan WANG ; Jian TAN ; Wei ZHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(1):30-34
Objective:To investigate the predictive value of early thyroid function changes on the efficacy of patients with Graves′ disease (GD) after 131I therapy. Methods:Data of patients with GD (59 males, 214 females; age (37.4±11.4) years) who underwent single therapy of 131I in Tianjin Medical University General Hospital from November 2017 to January 2019 were retrospectively analyzed. Symptoms, signs and laboratory tests (serum free triiodothyronine (FT 3) and serum free thyroxine (FT 4)) of patients were observed to assess the efficacy of 131I treatment. Efficacy was divided into complete remission (CR), partial remission (PR), non-remission (NR) or relapse. The changes of thyroid function (ΔFT 3=FT 3 before treatment-FT 3 after treatment)/FT 3 before treatment×100%; ΔFT 4=FT 4 before treatment-FT 4 after treatment)/FT 4 before treatment×100%) 1 month after 131I therapy in each efficacy group and differences among them were compared by using independent-sample t test, χ2 test, one-way analysis of variance and the least significant difference t test. ROC curves were drawn to analyze the predictive values of early thyroid function changes on the efficacy of 131I treatment for GD. Logistic regression analyses were performed to identify the influencing factors for the efficacy of 131I therapy. Results:CR rate and total effective rate of 273 GD patients after single therapy of 131I were 67.03%(183/273) and 92.67%(253/273), respectively. After 1 month, CR rate of euthyroidism group ( n=95) was significantly higher than that of hyperthyroidism group ( n=178; 81.05%(77/95) vs 59.55%(106/178); χ2=4.60, P=0.032). ΔFT 3 and ΔFT 4 at the first month were statistically significant and decreased sequentially in the CR group ( n=183), PR group ( n=70), NR or relapse groups ( n=20; F values: 15.40, 12.54, both P<0.001). ROC curve analysis showed that patients with ΔFT 3≥73.64% and (or) ΔFT 4≥59.03% had a higher probability of achieving CR, with sensitivities of 84.3% and 86.7%, and specificities of 62.6% and 62.6%, respectively. Logistic regression analysis showed that 24 h radioactive iodine uptake (odds ratio ( OR)=1.095, 95% CI: 1.031-1.139), dose of 131I given per gram of thyroid tissue ( OR=1.562, 95% CI: 1.321-1.694), ΔFT 3 ( OR=1.354, 95% CI: 1.295-1.482), ΔFT 4 ( OR=1.498, 95% CI: 1.384-1.608) were factors affecting the outcome of patients with GD treated with 131I treatment (all P<0.05). Conclusion:Effects of 131I treatment can be predicted based on the change of the thyroid function at the first month after 131I treatment in patients with GD.

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