1.Study of phenylpropanoids from Tripterygium hypoglaucum
Zhi-qi LIN ; Hong-bo ZHU ; Tang ZHOU ; Ji WANG ; Rong-ping ZHANG ; Xing-long CHEN
Acta Pharmaceutica Sinica 2024;59(6):1730-1740
This paper aimed to study phenylpropanoids of
2.Discrete element modeling and breakage behavior analysis of oral solid dosage form particles
Lin-xiu LUO ; Tian-bing GUAN ; An-qi LUO ; Zeng LIU ; Yu-ting WANG ; Yan-ling JIANG ; Zheng LU ; Jing-cao TANG ; Shuang-kou CHEN ; Hui-min SUN ; Chuan-yun DAI
Acta Pharmaceutica Sinica 2024;59(4):1057-1066
The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.
3.Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.
Quan GAO ; Lin LI ; Qi-Man ZHANG ; Qin-Song SHENG ; Ji-Liang ZHANG ; Li-Jun JIN ; Rui-Yan SHANG
Chinese journal of integrative medicine 2024;30(1):25-33
OBJECTIVE:
To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.
METHODS:
Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.
RESULTS:
The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.
CONCLUSION
Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Cell Proliferation
;
Matrix Metalloproteinase 9
;
Molecular Docking Simulation
;
Cell Cycle
;
ErbB Receptors
;
Apoptosis
;
Colorectal Neoplasms/pathology*
;
Cell Line, Tumor
4.Study on risk factors of mycobacterium tuberculosis infection among health workers in medical institutions
Lin HE ; Wei QI ; Shimiao TANG ; Hongwei CAO ; Yiwen JIANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(2):96-101
Objective:To understand the infection status of mycobacterium tuberculosis among health workers in tuberculosis designated medical institutions and explore the risk factors of infection.Methods:From September 2021 to June 2022, a questionnaire survey was conducted among health workers in relevant departments of 4 tuberculosis designated medical institutions by cluster stratified sampling, including the implementation of hospital infection control measures in medical institutions and occupational exposure of medical staff to mycobacterium tuberculosis. Peripheral blood interferon gamma release assays (IGRAs) and lung imaging examination were performed to determine the mycobacterium tuberculosis infection. Factors with statistical significance in univariate analysis were included in multivariate logistic regression to analyze the risk factors of mycobacterium tuberculosis infection.Results:A total of 657 people completed the lung imaging examination and questionnaire, of which 654 people had peripheral blood IGRAs detection, and the latent infection rate of tuberculosis was 39.45% (258/654) . Univariate analysis showed that age, sex, marital status, economic income, occupational category, professional title, length of service, and other variables had statistical significances in tuberculosis latent infection ( P<0.05) . In terms of personal health status, there were statistically significant differences in the distribution of health workers in terms of their tuberculosis history, tuberculosis history of their immediate family members, previous tuberculin skin test (TST) ( P<0.05) . Multivariate analysis showed that there were four risk factors related to tuberculosis, including professional title ( X1) , years of tuberculosis related works ( X2) , tuberculosis history ( X3) and previous TST ( X4) . The regression equation of the probability of tuberculosis among health workers was y=-1.920+0.246 X1+0.046 X2+1.231 X3+0.478 X4. Conclusion:The latent infection rate of tuberculosis among health workers in tuberculosis designated medical institutions is high. It is necessary to strengthen the management of infection control, carry out regular screening, enhance the self-protection awareness of health workers, and reduce their exposure to mycobacterium tuberculosis and infection risk.
5.Construction of a risk prediction model for overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with hepatitis B cirrhosis and portal hypertension
Lanjing WANG ; Jianping QIN ; Xin YAO ; Qi QI ; Lin LIU ; Shanhong TANG
Journal of Clinical Hepatology 2024;40(6):1149-1155
Objective To investigate the influencing factors for overt hepatic encephalopathy(OHE)in patients with hepatitis B cirrhosis after transjugular intrahepatic portosystemic shunt(TIPS),and to construct an individualized risk prediction model.Methods A total of 302 patients with hepatitis B cirrhosis who underwent TIPS in Department of Gastroenterology,The General Hospital of Western Theater Command,from January 2017 to December 2021 were enrolled,and according to the presence or absence of OHE after surgery,they were divided into non-OHE group with 237 patients and OHE group with 65 patients.The two groups were compared in terms of general data,laboratory markers,Child-Turcotte-Pugh(CTP)score,MELD combined with serum sodium concentration(MELD-Na)score,and albumin-bilirubin(ALBI)score before surgery.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.The univariate and multivariate logistic regression analyses were used to identify the influencing factors for OHE after TIPS in patients with hepatitis B cirrhosis,and independent influencing factors were used to construct a nomogram model.The receiver operating characteristic(ROC)curve analysis and the calibration curve analysis were used to evaluate the discriminatory ability and calibration of the model,and the decision curve analysis and the clinical impact curve(CIC)were used to evaluate the clinical effectiveness of the model.Results Age(odds ratio[OR]=1.035,95%confidence interval[CI]:1.004-1.066,P<0.05),white blood cell count(WBC)/platelet count(PLT)ratio(OR=33.725,95%CI:1.220-932.377,P<0.05),international normalized ratio(INR)(OR=5.149,95%CI:1.052-25.207,P<0.05),and pre-albumin(PAB)(OR=0.992,95%CI:0.983-1.000,P<0.05)were independent predictive factors for OHE after TIPS in patients with hepatitis B cirrhosis.The nomogram model constructed based on age,WBC/PLT ratio,INR,and PAB had an area under the ROC curve of 0.716(95%CI:0.649-0.781),with a sensitivity of 78.5%and a specificity of 56.1%.Conclusion The nomogram model constructed based on age,WBC/PLT ratio,INR,and PAB can help to predict the risk of OHE after TIPS in patients with hepatitis B cirrhosis.
6.Leukocyte cell-derived chemotaxin 2(LECT2)regulates liver ischemia-reperfusion injury
Dong MENG-QI ; Xie YUAN ; Tang ZHI-LIANG ; Zhao XUE-WEN ; Lin FU-ZHEN ; Zhang GUANG-YU ; Huang ZHI-HAO ; Liu ZHI-MIN ; Lin YUAN ; Liu FENG-YONG ; Zhou WEI-JIE
Liver Research 2024;8(3):165-171
Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.
7.Exploration on the Medication Rules of HUANG Li in Treating Recurrent Angina Pectoris After Percutaneous Coronary Intervention for Coronary Heart Disease
Shi-Yi TAO ; Xian-Wen TANG ; Lin-Tong YU ; De-Shuang YANG ; Rui-Qi YAO ; Lan-Xin ZHANG ; Jia-Yun WU ; Li HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1598-1606
Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.
8.Immune cell-mediated causal relationship between plasma metabolites and knee osteoarthritis:a Mendelian randomization study
Zhenyu WANG ; Hongmei ZHANG ; Lin JING ; Qi YAN ; Jixiang TANG ; Qirui GE
Military Medical Sciences 2024;48(10):778-785
Objective To evaluate both the causal relationship between plasma metabolites and the risk of knee osteoarthritis(KOA)and the potential mediating or masking effect of immune cells using Mendelian randomization(MR)systems.Methods The GWAS data on 1400 plasma metabolites,731 immune cell traits and KOA was retrieved from the genome-wide association study(GWAS)database.Two-way MR analysis was used to evaluate the causal relationship between plasma metabolism and KOA.Two-step mediation MR analysis was conducted to evaluate immune cell traits that might have mediating or masking effects.Results After sensitivity analysis and screening,65 plasma metabolites and 35 immune cell traits were found to have causal relationships with KOA(P<0.05).Mediation analysis found that CD45RA+CD28-CD8br%CD8br had a mediating effect in the causal relationship between three metabolites(2-hydroxyhi-ppurate,X-07765,X-23739)and the risk of KOA.2-hydroxyhippurate(salicylic acid)exerted a masking effect,and the effect ratio was 0.0412.Conclusion A variety of plasma metabolites and immune cell traits are causally related to KOA,which should not be regarded as a simple degenerative joint disease.The protective effect of salicylic acid against KOA may be weakened by its role in inducing the differentiation of Treg cells,which is worthy of more studies.
9.Comparison of the predictive value of multiparametric MRI and prostate-specific membrane antigen PET/CT for pelvic lymph node metastasis in prostate cancer
Wei TANG ; Yi CAI ; Yongxiang TANG ; Xiaoping YI ; Xiaomei GAO ; Lin QI
Chinese Journal of Surgery 2024;62(11):1008-1015
Objective:To compare the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT in detecting pelvic lymph node metastasis in prostate cancer.Methods:This is a retrospective case series study. A retrospective analysis was conducted on the data of 115 prostate cancer patients who underwent both mpMRI and PSMA PET/CT before undergoing radical prostatectomy and extended pelvic lymph node dissection at the Department of Urology, Xiangya Hospital, Central South University, between March 2020 and September 2023. The age ( M(IQR)) was 67(10) years (range: 45 to 84 years), and the body mass index was 24(4) kg/m 2 (range: 18 to 30 kg/m 2). Pathological and imaging data were obtained from the patients. Lymph node pathology results were used as the gold standard to evaluate the diagnostic performance of mpMRI and PSMA PET/CT for detecting pelvic lymph node metastasis in PCa through diagnostic evaluation tests. Comparisons between groups were performed using independent samples t-test, Mann-Whitney U test, or χ2 test. Results:The positive rate for detecting pelvic lymph node metastasis was 18.3% (21/115) with mpMRI and 25.2% (29/115) with PSMA PET/CT. The pathological positive rate for lymph nodes was 28.7% (33/115). In patient-based analysis, the diagnostic sensitivity of PSMA PET/CT was significantly higher than that of mpMRI (63.6% vs. 30.3%, χ2=7.36, P=0.007). In lesion-based analysis, both the sensitivity and positive predictive value of PSMA PET/CT were significantly higher than those of mpMRI (sensitivity: 68.0% vs. 21.6%, χ2=42.20, P<0.01; positive predictive value: 50.0% vs. 23.1%, χ2=7.54, P=0.006). Conclusions:PSMA PET/CT and mpMRI both demonstrates good specificity in predicting pelvic lymph node metastasis in prostate cancer. However, PSMA PET/CT is significantly superior to mpMRI in terms of sensitivity and the detection rate of pathologically positive lymph nodes.
10.Study on risk factors of mycobacterium tuberculosis infection among health workers in medical institutions
Lin HE ; Wei QI ; Shimiao TANG ; Hongwei CAO ; Yiwen JIANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(2):96-101
Objective:To understand the infection status of mycobacterium tuberculosis among health workers in tuberculosis designated medical institutions and explore the risk factors of infection.Methods:From September 2021 to June 2022, a questionnaire survey was conducted among health workers in relevant departments of 4 tuberculosis designated medical institutions by cluster stratified sampling, including the implementation of hospital infection control measures in medical institutions and occupational exposure of medical staff to mycobacterium tuberculosis. Peripheral blood interferon gamma release assays (IGRAs) and lung imaging examination were performed to determine the mycobacterium tuberculosis infection. Factors with statistical significance in univariate analysis were included in multivariate logistic regression to analyze the risk factors of mycobacterium tuberculosis infection.Results:A total of 657 people completed the lung imaging examination and questionnaire, of which 654 people had peripheral blood IGRAs detection, and the latent infection rate of tuberculosis was 39.45% (258/654) . Univariate analysis showed that age, sex, marital status, economic income, occupational category, professional title, length of service, and other variables had statistical significances in tuberculosis latent infection ( P<0.05) . In terms of personal health status, there were statistically significant differences in the distribution of health workers in terms of their tuberculosis history, tuberculosis history of their immediate family members, previous tuberculin skin test (TST) ( P<0.05) . Multivariate analysis showed that there were four risk factors related to tuberculosis, including professional title ( X1) , years of tuberculosis related works ( X2) , tuberculosis history ( X3) and previous TST ( X4) . The regression equation of the probability of tuberculosis among health workers was y=-1.920+0.246 X1+0.046 X2+1.231 X3+0.478 X4. Conclusion:The latent infection rate of tuberculosis among health workers in tuberculosis designated medical institutions is high. It is necessary to strengthen the management of infection control, carry out regular screening, enhance the self-protection awareness of health workers, and reduce their exposure to mycobacterium tuberculosis and infection risk.

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