1.Advances in oral distant targeted nanodelivery systems
Min SUN ; Chuan-sheng HUANG ; Li-ping WANG ; Xu-li RUAN ; Yun-li ZHAO ; Xin-chun WANG
Acta Pharmaceutica Sinica 2025;60(1):72-81
Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.
2.Association of serum adipokine CTRP6 in early pregnancy with gestational diabetes mellitus
Yaping XIN ; Qi ZHANG ; Yihan ZHU ; Mengmeng RUAN ; Xiaojing MA
China Modern Doctor 2024;62(9):26-29,32
Objective To study the expression levels of serum complement C1q/tumor necrosis factor-related protein 6(CTRP6)in women in early pregnancy and to explore its relationship with gestational diabetes mellitus(GDM).Methods Women at the Second Affiliated Hospital of Zhengzhou University from March 2021 to March 2022 were prospectively and consecutively selected from 10 to 13 weeks gestation for outpatient obstetric check-ups.The age,height,weight,and time of last menstruation of pregnant women were collected,and the levels of total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL),fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS)and CTRP6 were measured in early pregnancy,and the pre-pregnancy body mass index(BMI),baseline BMI,prenatal BMI,and homeostatic model assessment of insulin resistance(HOMA-IR)were calculated.All pregnant women underwent a 75g oral glucose tolerance test at 24-28 weeks of gestation and were divided into GDM group and normal glucose tolerance(NGT)group according to the test results.The clinical data and laboratory indexes of the two groups in early pregnancy were compared,and the correlation between serum CTRP6 and various indexes in early pregnancy and its relationship with GDM were analyzed.Results A total of 213 maternal cases were enrolled,and 203 cases were completed for follow-up.Among them,52 mothers were diagnosed with GDM,with a GDM prevalence rate of 25.62%.Serum CTRP6,age,pre-pregnancy BMI,baseline BMI,antenatal BMI,TC,LDL,FPG,HbA1c,FINS,and HOMA-IR were higher in GDM group compared to NGT group,with a statistically significant difference(P<0.05).CTRP6 in early pregnancy was positively correlated with age,pre-pregnancy BMI,baseline BMI,prenatal BMI,TG,LDL,FPG,HbA1c,FINS,HOMA-IR,and negatively correlated with HDL(P<0.05).After correcting for age,BMI,glycolipid metabolism index and HOMA-IR,CTRP6 in early pregnancy remained an independent factor in the development of GDM.Conclusion Elevated serum CTRP6 in early pregnancy is associated with GDM and is an independent risk factor for GDM.
3.The effect of Ba Duan Jin on the balance of community-dwelling older adults: a cluster randomized control trial
Leilei DUAN ; Yubin ZHAO ; Yuliang ER ; Pengpeng YE ; Wei WANG ; Xin GAO ; Xiao DENG ; Ye JIN ; Yuan WANG ; Cuirong JI ; Xinyan MA ; Cong GAO ; Yuhong ZHAO ; Suqiu ZHU ; Shuzhen SU ; Xin'e GUO ; Juanjuan PENG ; Yan YU ; Chen YANG ; Yaya SU ; Ming ZHAO ; Lihua GUO ; Yiping WU ; Yangnu LUO ; Ruilin MENG ; Haofeng XU ; Huazhang LIU ; Huihong RUAN ; Bo XIE ; Huimin ZHANG ; Yuhua LIAO ; Yan CHEN ; Linhong WANG
Chinese Journal of Epidemiology 2024;45(2):250-256
Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.
4.Expert consensus on the bi-directional screening for Mycobacterium tuberculosis and human immunodeficiency virus
Xin SHEN ; Yinzhong SHEN ; Eryong LIU ; Dingyong SUN ; Dongmin LI ; Yun HE ; Jinge HE ; Lin XU ; Bin CHEN ; Chengliang CHAI ; Lianguo RUAN ; Yong GAO ; Aihua DENG ; Zhen NING ; Jing CHEN ; Xiaofeng LIU ; Kaikan GU ; Lixin RAO
Shanghai Journal of Preventive Medicine 2024;36(4):327-336
Tuberculosis (TB) and human immunodeficiency virus infection / acquired immune deficiency syndrome (HIV/AIDS) are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years, with the promotion and application of new TB and HIV detection technologies worldwide, TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening, summarizes important progress of research and applications, and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.
5.Mechanism of the Development of Follicles Based on Cellular Force Transducer
Qingqing YANG ; Jifeng REN ; Xin RUAN ; Pengxu WANG ; Xiaoying DONG
Journal of Medical Biomechanics 2024;39(5):992-997
Cellular force transducer plays a crucial role in normal development of the follicles,which consists of integrin,focal adhesion,signal pathways and cytoskeleton.In follicle development,cellular force transducer converts force stimulation into biochemical signal,and activates the signal pathways to make cytoskeleton respond to stimulation.This process promotes various biological functions of germ cells,such as migration,meiosis and ovulation.This review summarizes the mechanism of follicles'development from two aspects,the role of cellular force transducer in the development of follicles and the related signal pathways,so as to provide a new idea for the further study of follicle development.
6.The efficacy of simultaneous single shot-echo planar imaging and readout segment of long variable echo trains sequences diffusion-weighted imaging for diagnosis of malignant breast lesions
Hui ZHANG ; Yanfen XIN ; Yongmeng ZHU ; Junyu GUO ; Yuning PAN ; Xinzhong RUAN
Chinese Journal of Radiology 2024;58(3):279-285
Objective:To compare the image quality and the diagnostic efficiency for breast malignant lesions using simultaneous multi-slice single shot echo planar imaging (SMS+SS-EPI) and readout segment of long variable echo trains (RESOLVE) for breast diffusion-weighted imaging (DWI).Methods:This study was a cross-sectional study. Clinical and imaging data of 102 patients with breast lesion from March 2021 to February 2023 in the First Hospital Affiliated to Ningbo University were prospectively analyzed. All patients underwent routine breast MRI scans and cross-sectional RESOLVE and SMS+SS EPI sequence DWI, and the image quality of 2 types sequences of DWI was evaluated. The subjective evaluation was based on a 5-point scale, including geometric distortion, artifact blurring, fat suppression, overall image quality, and lesion conspicuity of the breast. The objective evaluation included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) value of the lesion. Wilcoxon signed rank sum test was used to compare the subjective and objective parameters between the two sequences. Finally, the receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the effectiveness of ADC values for diagnosing breast malignant lesions based on two sequence images.Results:All 102 female patients had single lesions, aged from 25 to 68 years and 60 lesions were malignant and 42 were benign. The acquisition time for SMS+SS-EPI sequence imaging was 1 min 50 s, and the acquisition time for RESOLVE sequence imaging was 3 min 43 s.The subjective scores from both SMS+SS-EPI and RESOLVE sequence were over than 3 points. The geometric distortion, artifact blurring, and overall image quality scores of RESOLVE sequence images were higher than those of SMS+SS-EPI (all P<0.001). The overall lesion conspicuity score, malignant lesion conspicuity score, and benign lesion conspicuity score of DWI and ADC images combined with SMS+SS-EPI sequence were higher than those of the RESOLVE sequence (all P<0.05). There were no statistically difference in SNR, CNR, overall ADC value, malignant ADC value, and benign ADC value between SMS+SS-EPI and RESOLVE sequence DWI images of breast lesions (all P>0.05). The AUC of RESOLVE sequence ADC value in diagnosis of breast cancer was 0.973, the sensitivity was 0.929, and the specificity was 0.915; The AUC of SMS+SSC-EPI sequence ADC value in diagnosis of breast cancer was 0.956, the sensitivity was 0.977, and the specificity was 0.850. Conclusions:In breast DWI, the subjective score of SMS+SS EPI image quality can basically meet the diagnostic requirements and the conspicuity of lesions is better than that of the RESOLVE sequence. Both have good diagnostic efficacy for malignant breast lesions.
7.Analysis of the types and functions of CD34 + cells in full-thickness skin defect wounds of normal mice and diabetic mice by single-cell RNA sequencing
Jia HE ; Jingru WANG ; Wenjun GAN ; Guiqiang LI ; Qi XIN ; Zepeng LIN ; Shubin RUAN ; Xiaodong CHEN
Chinese Journal of Burns 2024;40(3):230-239
Objective:To analyze the types and functions of CD34 + cells in full-thickness skin defect wounds of normal mice and diabetic mice by single-cell RNA sequencing. Methods:This study was an experimental study. The CD34 + cell lineage tracing mouse was produced, and the visualization of CD34 + cells under the fluorescent condition was realized. Six male CD34 + cell lineage tracing mice aged 7-8 weeks (designated as diabetic group) were intraperitoneally injected with streptozotocin to establish a diabetic model, and full-thickness skin defect wounds were prepared on their backs when they reached 13 weeks old. Another 6 male CD34 + cell lineage tracing mice aged 13 weeks (designated as control group) were also subjected to full-thickness skin defect wounds on their backs. On post-injury day (PID) 4, wound tissue was collected from 3 mice in control group and 2 mice in diabetic group, and digested to prepare single-cell suspensions. CD34 + cells were screened using fluorescence-activated cell sorting, followed by single-cell RNA sequencing. The Seurat 4.0.2 program in the R programming language was utilized for dimensionality reduction, visualization, and cell clustering analysis of CD34 + cell types, and to screen and annotate the marker genes for each CD34 + cell subpopulation. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis was performed to analyze the differentially expressed genes (DEGs) of CD34 + fibroblasts (Fbs), smooth muscle cells (SMCs), keratinocytes (KCs), and chondrocyte-like cells (CLCs) in the wound tissue of two groups of mice for exploring cellular functions. Results:On PID 4, CD34 + cells in the wound tissue of both groups of mice were consisted of 7 cell types, specifically endothelial cells, Fbs, KCs, macrophages, T cells, SMCs, and CLCs. Among these, Fbs were further classified into 5 subpopulations. Compared with those in control group, the proportions of CD34 + endothelial cells, Fbs subpopulation 1, Fbs subpopulation 4, KCs, and CLCs in the wound tissue of mice were increased in diabetic group, while the proportions of CD34 + Fbs subpopulation 2, Fbs subpopulation 3, and SMCs were decreased. The marker genes for annotating CD34 + CLCs, endothelial cells, Fbs subpopulation 1, Fbs subpopulation 2, Fbs subpopulation 3, Fbs subpopulation 4, Fbs subpopulation 5, KCs, macrophages, SMCs, and T cells were respectively metastasis-associated lung adenocarcinoma transcript 1, fatty acid binding protein 4, Gremlin 1, complement component 4B, H19 imprinted maternally expressed transcript, Dickkopf Wnt signaling pathway inhibitor 2, fibromodulin, keratin 5, CD74 molecule, regulator of G protein signaling 5, and inducible T-cell co-stimulator molecule. KEGG and GO enrichment analysis revealed that, compared with those in control group, DEGs with significant differential expression (SDE) in CD34 + Fbs from the wound tissue of mice in diabetic group on PID 4 were significantly enriched in terms related to inflammatory response, extracellular matrix (ECM) organization, regulation of cell proliferation, and aging (with Pvalues all <0.05), DEGs with SDE in CD34 + SMCs were significantly enriched in terms related to cell migration, apoptotic process, positive regulation of transcription, and phagosome (with P values all <0.05), DEGs with SDE in CD34 + KCs were significantly enriched in terms related to mitochondrial function, transcription, and neurodegenerative diseases (with P values all <0.05), and DEGs with SDE in CD34 + CLCs were significantly enriched in terms related to rhythm regulation, ECM, and viral infection (with P values all <0.05). Conclusions:CD34 + cells display high heterogeneity in the healing process of full-thickness skin defect wounds in both normal mice and diabetic mice. The significantly enriched functions of DEGs with SDE in CD34 + cell subpopulations in the wound tissue of the two mouse groups are closely related to the wound healing process.
8.Clinical effect of Longqing tablets combined with antibiotics on improving stent-related symptoms and urinary tract infections in patients with indwelling ureteral stent
Qi WANG ; Xin CUI ; Jiangtao WU ; Hao YAN ; Jimeng RUAN
International Journal of Surgery 2024;51(10):654-659
Objective:To evaluate the effects of antibiotics alone and combined with Longqing tablets and antibiotics on stent-related symptoms (SRS), urinary tract infection (UTI), and quality of life in patients who underwent ureteroscopic lithotripsy (URL) with indwelling ureteral stents.Methods:The clinical data of 160 patients who underwent URL with indwelling ureteral stents in the Department of Urology, Xuanwu Hospital, Capital Medical University from January 2022 to December 2023 were retrospectively analyzed. According to the postoperative application of antibiotics and Longqing tablets, they were divided into two groups: control group and observation group, with 80 cases in each group. The control group took Levofloxacin tablets orally, and the observation group took Longqing tablets combined with Levofloxacin tablets orally. The SRS of the two groups was compared according to the degree of urinary tract irritation symptoms, low back pain, and dysuria. UTI was evaluated by the incidence of fever, hematuria, pyuria, positive rate of urine culture, and specific bacterial classes. The Chinese version of the ureteral stent symptom questionnaire (USSQ) and the quality of life score were evaluated in the two groups. Normally distributed quantitative data were expressed as mean ± standard deviation ( ± s), and the t-test was used for comparison between groups; non-normally distributed quantitative data were expressed as median (interquartile range) [ M( Q1, Q3)], and the non-parametric test was used for comparison between groups. Count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Results:Among the 160 patients, 141 (88.13%) developed SRS, including 71 cases (88.75%) in the control group, and 70 cases (87.50%) in the observation group, there was no significant difference between the two groups ( P=0.724). In terms of SRS, the urinary tract irritation symptom scores [3.0 (1.0, 5.0) points vs 5.0 (3.0, 7.0) points], low back pain scores [1.5 (1.0, 2.0) points vs 2.5 (2.0, 3.0) points] and dysuria scores [1.5 (1.0, 2.0) points vs 3.5 (2.5, 4.0) points] of the observation group were significantly lower than those of the control group, the differences were statistically significant ( P<0.05). The Chinese version of USSQ showed that the urinary tract symptoms of the observation group were significantly relieved compared with the control group [15(12, 19) points vs 22 (15, 28) points], and the difference was statistically significant ( P=0.037). In terms of UTI, the incidence of fever (6.25% vs 7.50%), the incidence of hematuria (20.00% vs 22.50%), the incidence of pyuria (30.00% vs 33.75%), and positive rate of urine culture (11.25% vs 15.00%) between the two groups were not statistically significant ( P> 0.05), but the number was reduced to a certain extent. There was no statistically significant difference in the scores of physiological function, emotional function and social function between the two groups before surgery ( P> 0.05); however, the scores of the above three items in both groups were improved 2 weeks after surgery, and the improvement of the observation group was significantly higher than that of the control group, with statistical significance ( P<0.01). Conclusion:Longqing tablets combined with antibiotics are more effective in improving SRS in patients who receive URL and have indwelling ureteral stents than antibiotics alone, and can prevent UTI and improve the quality of life to a certain extent.
9.Effect of different expression levels of GRIM-19 on the resistance of prostate cancer cells to docetaxel chemotherapy
Hai-Li LIN ; Yong-Xin HE ; Tian-Qi LIN ; Zai-Xiong SHEN ; Liu-Tao LUO ; Si-Xing HUANG ; Yi HUANG ; Yu ZHOU ; Min-Yi RUAN
National Journal of Andrology 2024;30(10):884-888
Objective:To investigate the effect of GRIM-19 on the resistance of carcinoma cells to the chemotherapeutic agent docetaxel in the treatment of PCa.Methods:Using siRNA technology to interfere with the gene expression in PCa cells,we estab-lished a model of GRIM-19 overexpression/knockdown in PCa cells.We investigated the effect of different expression levels of GRIM-19 on docetaxel-induced death of the PCa cells by qPCR,Western blot and flow cytometry,and assessed the value of GRIM-19 in re-ducing the chemotherapy-resistance of PCa cells.Results:GRIM-19 was down-regulated in PCa tissues and cells.Knockout of GRIM-19 significantly decreased the expression of siGRIM19 in the PC-3 and LNCaP cells,and reduced their death rate when treated with docetaxel compared with the control group.The expressions of GRIM-19 mRNA and protein were remarkably upregulated after transfection with GRIM-19,and the overexpressed GRIM-19 promoted the death of the PC-3 and LNCaP cells treated with docetaxel in a dose-dependent manner.Flow cytometry analysis showed a lower apoptosis rate of PC-3-R cells than that of PC-3 cells at different time points of docetaxel-induction at different doses.Conclusion:GRIM-19 is a PCa suppressor gene with a significant facilitating effect on the apoptosis of PCa cells,and the overexpression of GRIM-19 promotes docetaxel-induced PCa cell death and improves the sensitivity of chemotherapy.
10.Study on the relationship between serum CTRP13 and gestational diabetes mellitus and pregnancy outcome
Yaping XIN ; Xiaojing MA ; Mengmeng RUAN ; Qi ZHANG ; Xuanyan HUANG
China Modern Doctor 2024;62(19):75-79
Objective To explore the relationship between C1q tumor necrosis factor related protein 13(CTRP13)and gestational diabetes mellitus(GDM),and the predictive value of CTRP13 for adverse pregnancy outcomes in GDM patients.Methods A total of 163 pregnant women who underwent prenatal examination in the Second Affiliated Hospital of Zhengzhou University from January to May 2023 were enrolled in GDM group(n=83)and normal glucose tolerance(NGT)group(n=80)according to the results of oral glucose tolerance test at 24-28 weeks of gestation.Collect general information,biochemical data,and adverse pregnancy outcomes from two groups of subjects.Analyze the correlation between serum CTRP13 and glucose and lipid metabolism indicators in GDM pregnant women.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of CTRP13 for adverse pregnancy outcomes in GDM pregnant women.Results The pre pregnancy body mass index,prenatal body mass index,triglycerides,total cholesterol,low density lipoprotein,fasting blood glucose,2-hours plasma glucose,glycosylated hemoglobin,fasting insulin,and homeostasis model assessment of insulin resistanc index in GDM group was significantly higher than those in NGT group,while CTRP13 was significantly lower than that in NGT group(P<0.05).Serum CTRP13 was negatively correlated with total cholesterol,triglycerides,low density lipoprotein,2-hours plasma glucose,and glycosylated hemoglobin in GDM patients(P<0.05).The incidence of adverse pregnancy outcomes such as gestational hypertension and premature rupture of membranes in GDM group were significantly higher than those in NGT group(P<0.05).The area under the curve of serum CTRP13 for predicting adverse pregnancy outcomes in GDM pregnant women was 0.805,with sensitivity and specificity of 75.80%and 76.00%,respectively.Conclusion Serum CTRP13 is associated with glucose and lipid metabolism in GDM pregnant women,and is a potential biomarker for predicting adverse pregnancy outcomes in GDM pregnant women.

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