1.Visual feature extraction combining dissolution testing for the study of drug release behavior of gliclazide modified release tablets
Si-yu CHEN ; Ze-ya LI ; Ping LI ; Xin-qing ZHAO ; Tao GONG ; Li DENG ; Zhi-rong ZHANG
Acta Pharmaceutica Sinica 2025;60(1):225-231
Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the
2.The Effect of Mitochondrial Damage in Chondrocytes on Osteoarthritis
Zhen-Wei LI ; Jing-Yu HOU ; Yu-Ze LIN ; Zhi-Qi ZHANG ; Shang-Yi LIU ; Xiao-Wen LIU ; Kang-Quan SHOU
Progress in Biochemistry and Biophysics 2024;51(7):1576-1588
The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.
3.Low-dose Radiation Therapy for Osteoarthritis
Guo-Rong MA ; Yong-Ze YANG ; Xin MENG ; Yu-Ting GAO ; Shu-Zhi LI ; Hong-Zhang GUO ; Xiao-Dong JIN
Progress in Biochemistry and Biophysics 2024;51(6):1382-1392
Osteoarthritis (OA) is a chronic degenerative joint disease and the most common type of arthritis. It involves almost any joint and can lead to chronic pain and disability. In the late 19th century, Roentgen discovered X-rays, and then began to use radiotherapy to treat tumors. In the 1980s, Luckey thought that low-level radiation (LDRT) might be beneficial to biology, and it was gradually applied to the treatment of some diseases. This paper introduces the epidemiology, risk factors, clinical manifestations and treatment methods of OA, points out that the cartilage injury and the important effect of synovial inflammation in the pathogenesis of OA, namely when the homeostasis of articular cartilage are destroyed, synthetic metabolism and catabolism imbalances, cartilage cells damaged their breakdown products consumed by synovial cells. Synovial cells and synovial macrophages secrete proinflammatory cytokines, metalloproteinases and proteolytic enzymes, leading to cartilage matrix degradation and chondrocyte damage, which aggravates synovial inflammation and cartilage damage, forming a vicious cycle. The possible mechanism and clinical research progress of LDRT in alleviating OA are discussed. LDRT can regulate inflammatory response, inhibit the production of pro-inflammatory cytokines, and promote the production of anti-inflammatory cytokines, thereby achieving anti-inflammatory effect. Studies have shown that after irradiation, the expression of inducible nitric oxide synthase (iNOS) was decreased, the release of reactive oxygen species (ROS) and the production of superoxide were inhibited, the anti-inflammatory phenotype of macrophages was differentiated from M1 to M2, the inflammatory CD8+ T cells were transformed into CD4+ T cells, and the number of dendritic cells (DC) was significantly reduced. LDRT inhibit the production of proinflammatory factors in leukocytes, reduce their recruitment and adhesion, and down-regulate the expression levels of cell adhesion molecules such as selectin, intercellular adhesion molecule (ICAM) and vascular endothelial cell adhesion molecule (VCAM). LDRT can regulate endothelial cells, stimulate endothelial cells to produce a large amount of TGF-β1, reduce the adhesion of endothelial cells to peripheral blood mononuclear cells (PBMC), and contribute to the anti-inflammatory effect of LDRT. It also exerted anti-inflammatory effects by regulating mitochondrial growth differentiation factor 15 (GDF15). After low-level radiation, the MMP-13 (matrix metalloproteinases-13) and the ADAMTS5 (recombinant a disintegrin and metalloproteinase with thrombospondin-5) decreased, the Col2a1 (collagen type 2) increased in chondrocytes. In the existing clinical studies, most patients can achieve relief of joint pain and recovery of joint mobility after irradiation, and the patients have good feedback on the efficacy. The adverse reactions (acute reactions and carcinogenic risks) caused by LDRT in the treatment of OA are also discussed. During the treatment of OA, a few patients have symptoms such as redness, dryness or itching at the joint skin, and the symptoms are mild and do not require further treatment. Patients are thus able to tolerate more frequent and longer doses of radiotherapy. In general, LDRT itself has the advantages of non-invasive, less adverse reactions, and shows the effect of pain relief and movement improvement in the treatment of OA. Therefore, LDRT has a broad application prospect in the treatment of OA.
4.A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement
Hua ZHENG ; Yunfei ZHI ; Lujing YING ; Lan ZHU ; Mingliang JI ; Ze LIANG ; Jiangshan WANG ; Haifeng SHI ; Weihong ZHANG ; Mengsu XIAO ; Yushi ZHANG ; Kaifeng XU ; Zhaohui LU ; Yaping LIU ; Ruiyi XU ; Huijuan ZHU ; Li WEN ; Yan ZHANG ; Gang CHEN ; Limeng CHEN
JOURNAL OF RARE DISEASES 2024;3(1):79-86
Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.
5.Bioequivalence study of etoricoxib tablets in healthy Chinese subjects
Zhen-Zhen JIAO ; Li XU ; Man LIU ; Tian-Ze HU ; Dan SONG ; Xiao-Juan WANG ; Zhi-Jing ZHAO ; Hui-Chen LIU
The Chinese Journal of Clinical Pharmacology 2024;40(5):718-722
Objective To study the pharmacokinetic characteristics of etoricoxib tablets in healthy Chinese subjects and to evaluate the bioequivalence and safety of the test and reference formulations.Methods In a randomised,single-dose,two-period,two-sequence crossover trial,28 healthy subjects were enrolled under the fasting and fed conditions,respectively,who received a single oral dose of 60 mg of etoricoxib tablets in the test or reference formulation.The concentration of etoricoxib in plasma was detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated to evaluate bioequivalence and using WinNonlin 8.2 software.Results The main pharmacokinetic parameters of the test and reference preparations were as follows:The fasting condition Cmax of etoricoxib were(1 176.96±287.95)and(1 164.93±189.65)ng·mL-1;AUC0-t were(18 651.95±6 100.27)and(19 241.39±6 107.48)ng·h·mL-1;and AUC0-∞ were(19 939.15±7 553.27)and(20 536.31±7 223.40)ng·h·mL-1.The fed condition Cmax of etoricoxib were(913.50±184.72)and(878.59±164.35)ng·mL-1;and AUC0-t were(19 085.22±5 155.01)and(18 669.54±4 508.21)ng·h·mL-1;AUC0-∞ were(20 103.77±5 567.02)and(19 528.05±4 989.74)ng·h·mL-1.The 90%confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters in the fasting and fed conditions fell between 80.00%and 125.00%.The incidence of adverse events in the fasting and fed conditions were 28.57%and 21.43%,respectively.Conclusion Two kinds of etoricoxib tablets are bioequivalent,and have similar safety in healthy Chinese subjects.
6.Knockdown of Runx1 enhances the inhibitory effects of arterial interventional chemotherapy on tumor invasion and metastasis in lung cancer rats
Xi-Yao ZHANG ; Ze-Xin WANG ; Li-Jun GUAN ; Zhi-Chao WANG ; Meng-Ruo XUE
The Chinese Journal of Clinical Pharmacology 2024;40(20):3008-3012
Objective To investigate the role of inhibition of Runt-associated transcription factor 1(Runx1)expression in arterial interventional chemotherapy for lung cancer in rats.Methods A549 cells were randomly divided into control group(normal cultured cells),si-NC group(transfected with si-NC plasmid),si-Runx1 group(transfected with si-Runx1 plasmid).Cell proliferation was detected by cell counting kit-8(CCK-8)assay,and the relative expression level of protein was detected by Western blotting.Rats were randomly divided into model group(constructed lung cancer transplanted tumor rats),sh-Runx1 group(knockdown Runx1 expression),OXA arterial group(single arterial interventional chemotherapy),sh-Runx1+OXA group(knockdown Runx1+intravenous chemotherapy),sh-Runx1+OXA arterial group(knockdown Runx1+arterial interventional chemotherapy).After continuous treatment for 3 weeks,tumor volume and weight were measured,TdT mediated dUDP nick end labeling(Tunel)assay was used to detect tumor apoptosis,and Western blot assay was used to detect the expression of migration and invasion-related proteins.Results The survival rates of A549 cells in the control group,si-NC group and si-Runx1 group were(100.00±5.13)%,(99.56±3.44)%and(60.96±7.00)%,respectively;the expression levels of Runx1 protein were 0.84±0.06,0.85±0.06 and 0.20±0.03,respectively.Compared with the control group and si-NC group,the cell survival rate and Runx1 protein expression level in the si-Runx1 group were significantly decreased(all P<0.05).The tumor volume of the model group,sh-Runx1 group,OXA arterial group,sh-Runx1+OXA group and sh-Runx1+OXA arterial group after the last treatment were(1 069.58±121.79),(819.30±6.98),(639.34±66.64),(486.91±29.88),(416.57±21.58)mm3,respectively;the apoptosis rates were(4.32±0.36)%,(13.95±1.22)%,(15.46±1.14)%,(23.71±2.01)%,(31.16±3.04)%,respectively;the expression levels of E-cadherin protein were 0.31±0.05,0.61±0.07,0.67±0.09,0.92±0.07,1.23±0.13,respectively.The above indexes of sh-Runx1 group,OXA arterial group,sh-Runx1+OXA group and sh-Runx1+OXA arterial group were compared with those of the model group,and the difference was statistically significant(all P<0.05).The above indexes of sh-Runx1+OXA arterial group were compared with those of sh-Runx1,OXA arterial group and sh-Runx1+OXA group,and the difference was statistically significant(all P<0.05).Conclusion inhibition of Runx1 can enhance the apoptosis induction and cell metastasis inhibition of arterial interventional chemotherapy in lung cancer rats.
7.RNA SNP Detection Method With Improved Specificity Based on Dual-competitive-padlock-probe
Qin-Qin ZHANG ; Jin-Ze LI ; Wei ZHANG ; Chuan-Yu LI ; Zhi-Qi ZHANG ; Jia YAO ; Hong DU ; Lian-Qun ZHOU ; Zhen GUO
Progress in Biochemistry and Biophysics 2024;51(11):3021-3033
ObjectiveThe detection of RNA single nucleotide polymorphism (SNP) is of great importance due to their association with protein expression related to various diseases and drug responses. At present, splintR ligase-assisted methods are important approaches for RNA direct detection, but its specificity will be limited when the fidelity of ligases is not ideal. The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection. MethodsIn this study, a dual-competitive-padlock-probe (DCPLP) assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation. To verify the method, we employed dual competitive padlock probe-mediated rolling circle amplification (DCPLP-RCA) to genotype the CYP2C9 gene. ResultsThe specificity was well improved through the competition and strand displacement of dual padlock probe, with an 83.26% reduction in nonspecific signal. By detecting synthetic RNA samples, the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L. Furthermore, clinical samples were applied to the method to evaluate its performance, and the genotyping results were consistent with those obtained using the qPCR method. ConclusionThis study has successfully established a highly specific direct RNA SNP detection method, and provided a novel avenue for accurate identification of various types of RNAs.
8.Antipyretic and anti-inflammatory effects and quality evaluation of a new type of Lonicera Japonicae Flos granule raw decoction piece
Zhi-jun GUO ; Meng-meng HOU ; Dan GAO ; Yu-han WU ; Ze-min YANG ; Jia-lu WANG ; Bo GAO ; Xi-wen LI
Acta Pharmaceutica Sinica 2024;59(7):2087-2097
Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional
9.Quantitative Evaluation of Latent Fingerprints Developed by Fluorescent Methods Based on Python
Zhuo-Hong YU ; Zhi-Ze XU ; Meng WANG ; Wen-Zhuo FAN ; Jie LI ; Ming LI ; Chuan-Jun YUAN
Chinese Journal of Analytical Chemistry 2024;52(7):964-974,中插1-中插12
A serious of rare earth luminescent micro/nano-materials with various properties were synthesized via chemical method for fluorescent development of latent fingerprints(LFPs).Three evaluation indexes namely contrast,sensitivity and selectivity were introduced to evaluate the effects of LFP development.Quantitative formulas for calculating the contrast,sensitivity and selectivity were further put forward,and a quality evaluation system based on Python was thus established.In addition,the objective evaluation value was finally confirmed to be consistent with the subjective visual judgment.The reproducibility of this evaluation method was finally confirmed.The effects of luminescence intensity and color of developing materials on the contrast,particle size of developing materials on the sensitivity,and micromorphology and surface property of developing materials on the selectivity were discussed in detail.Five effective ways were also proposed to promote the quality of LFP development,such as increasing the luminescence intensity,tuning the luminescence color,decreasing the particle size,adjusting the micromorphology,and modifying the surface property.This quality evaluation system based on Python could evaluate the effects of LFP development objectively,accurately and comprehensively,exhibiting easy operability,high efficiency,sensitive response,accurate and reliable results,and wide applicability,which would provide beneficial references for the reasonable selection of LFP development methods as well as objective evaluation of evidence value.
10.A nomogram model based on CT imaging features to predict the pathological risk classification of small intestinal stromal tumors
Ying XU ; Weihua ZHI ; Lu LI ; Ze TENG ; Huiqin ZHANG ; Feng YE ; Xinming ZHAO
Chinese Journal of Radiology 2024;58(10):1063-1068
Objective:To explore the value of the imaging nomogram model based on preoperative CT features of patients with small intestinal stromal tumor (SIST) in predicting pathological risk classification.Methods:This was a cohort study. The patients who were diagnosed as primary SIST by postoperative pathology in Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to October 2023 were retrospectively included. According to the modified 2008 National Institutes of Health classification criteria, the patients were divided into a pathological intermediate/high-risk group (86 cases) and a very low/low-risk group (56 cases). The features of preoperative enhanced CT images of SIST were analyzed, including tumor boundary, necrosis, intra-tumoral hemorrhage, intra-tumoral calcification, growth pattern, enhancement pattern, enhancement degree, enlarged vessels feeding or draining the mass (EVFDM), and tumor location. Patients were followed up to determine the recurrence-free survival (RFS). Univariate and multivariate logistic regression were used to screen the independent predictors of SIST with pathological medium/high-risk group. The independent predictors were combined to construct an imaging prediction model, and a nomogram was drawn. The receiver operating characteristic curve was used to evaluate the predictive efficacy of the model. The Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the differences in RFS.Results:Univariate logistic regression results showed that tumor shape, necrosis, intra-tumoral hemorrhage, EVFDM, and tumor location were potentially related to medium/high-risk SIST. Multivariate logistic regression results showed that tumor shape ( OR=3.92, 95% CI 1.58-9.71, P=0.003), necrosis ( OR=4.60, 95% CI 1.91-11.09, P<0.001), and EVFDM ( OR=6.25,95% CI 1.74-22.47, P=0.005) were independent predictors of pathological intermediate/high-risk SIST. The area under the curve of the imaging predictive model combining the three predictors to predict the intermediate/high-risk SIST was 0.835 (95% CI 0.769-0.901), the sensitivity was 0.810, the specificity was 0.839, and the accuracy was 0.789. Taking the cut-off value (0.810) as the boundary value, the patients were divided into the high-risk group (74 cases) and the low-risk group (68 cases) according to the prediction results. The median RFS of the predicted high-risk group was poorer than that of the predicted low-risk group, and the difference was statistically significant ( χ2=5.20, P=0.023). Conclusions:The imaging nomogram model based on preoperative CT image features shape, necrosis, and EVFDM can effectively predict the pathological intermediate/high-risk SIST before surgery and has important predictive value for postoperative recurrence.

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