1.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
2.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
3.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
4.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
5.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
6.Establishment of pharmaceutical care pathway based on the problems related to chemotherapy
Ya CHEN ; Tingrong YANG ; Hua ZHAO ; Ying WANG
China Pharmacy 2024;35(3):368-373
OBJECTIVE To design pharmaceutical care pathway for the problems related to chemotherapy, and to evaluate whether it contributes to the detection and intervention of drug-related problems (DRPs) in chemotherapy patients. METHODS The pharmaceutical care pathway table and flow charts were constructed and implemented by pharmaceutical care practice experience. The patients who were admitted to our hospital for chemotherapy before and after the implementation of the pharmaceutical care pathway were divided into control group (before the implementation,60 cases) and observation group (after the implementation,64 cases), respectively; the relevant medical records of patients in the control group were extracted to evaluate DRPs, and pharmaceutical care of chemotherapy-related problems was performed for patients in observation group to extract DRPs. The basic condition, chemotherapy condition, DRPs classification and intervention status, adverse reactions induced by chemotherapy, PCNE classification of DRPs, occurrence time of DRPs, and drug classes related to DRPs were compared between 2 groups. RESULTS There was no statistical significance in the basic situation, chemotherapy regimen and chemotherapy drug category between the two groups (P>0.05). DRPs occurred in 46 and 37 patients in control group and observation group, respectively. In both groups, DRPs mainly occurred during chemotherapy, and mainly in the early stage of chemotherapy. Using the new pathway, the detection of DRPs significantly increased from 52.17% in the control group to 91.89% in the observation group (P<0.05). The successful intervention rate of DRPs was significantly increased from 32.61% in the control group to 72.97% in the observation group (P< 0.05). The incidence of adverse drug reactions significantly decreased from 28.33% in the control group to 12.50% in the observation group(P<0.05). The main problem type of DRPs in the control group was treatment effectiveness, which mainly involved adjuvant antitumor drugs, mainly due to the use of adjuvant anti-tumor drugs for off-label prescribing; that of the observation group was treatment effectiveness and treatment safety, which mainly involved vomiting drugs, mainly due to insufficient medication to prevent nausea and vomiting caused by chemotherapy. CONCLUSIONS The implementation of the pathway helps clinical pharmacists to detect and intervene in DRPs among chemotherapy patients, and reduces the occurrence of chemotherapy-induced adverse reactions.
7.Determination of aspirin and salicylic acid of children with Kawasaki disease by HPLC-IDMS
Ying-Hua MA ; Yi-Le ZHAO ; Ya-Bin QIN ; Ying-Qian ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(8):1203-1207
Objective To establish a method for determination of aspirin(ASP)and salicylic acid(SA)in plasma of children with kawasaki disease by high performance liquid chromatography-isotope dilution mass spectrometry(HPLC-IDMS).Methods The samples were pre-treated by precipitation protein method with organic solvent.ASP-D4 and SA-D4 were used as isotope internal standards.Chromatographic column:Phenomenex Kinetex? XB C18(2.6 mm × 50.0 mm,3.0μm);flow phase:0.1%formic acid-water(A)and acetonitrile(B),gradient elution;flow speed:0.5 mL·min-1;injection volume:6 μL.The detection method of mass spectrometry was negative ion mode,multireaction monitoring mode for quantitative analysis.Results The linear range of aspirin was 1.02-4 000 ng·mL-1(r2=0.995 4),and lower limit of quantification(LLOQ)was 1.02 ng·mL-1.The linear range of salicylic acid was 1.28-5 000 ng·mL-1(r2=0.998 5),and LLOQ was 1.28 ng·mL-1.Accuracy,precision,matrix effect and stability were in line with the provisions of Chinese Pharmacopoeia(2020 edition).Conclusion This study determined the blood concentration of aspirin and salicylic acid in children with HPLC-IDMS,which is rapid,simple,stable,economical,and high specificity.It can be applied to therapeutic drug monitoring of aspirin and salicylic acid in clinical children with kawasaki disease.
8.Correlation between serum homocysteine and quantitative electroencephalogram and prognosis of cerebral hemorrhage
Ya OU ; Pingshu ZHANG ; Xiaodong YUAN ; Lili ZHANG ; Jing WANG ; Ying ZHAO ; Bin XU ; Qian MA
Clinical Medicine of China 2024;40(2):88-95
Objective:To explore the predictive value of admission serum homocysteine levels and quantitative electroencephalogram (qEEG) indicators for adverse outcomes in patients with cerebral hemorrhage.Methods:A retrospective study was conducted on 89 patients, who were collected as the study objects with hemorrhagic stroke treated in the neurology intensive care unit at Kailuan General Hospital from January 2017 to December 2022. Patients were categorized into two groups based on modified Rankin Scale (mRS) scores at discharge: a good prognosis group (mRS≤2) and a poor prognosis group (mRS 3-6). Clinical data and qEEG monitoring of various brain regions were collected. The impact factors of hemorrhagic prognosis were analyzed using multifactorial logistic regression. ROC curve analysis was performed to assess the predictive value of qEEG and admission homocysteine levels for adverse outcomes in hemorrhagic stroke patients.Results:(1) The age of the poor prognosis group was higher than that of the good prognosis group((66.51+13.64) to (60.53+11.69), t=2.15, P=0.034) and admission serum homocysteine levels were significantly higher in the poor prognosis group than in the good prognosis group (17.28(15.52,24.72)mmol/L to 14.50(10.28,16.00)mmol/L, Z=4.14, P<0.001). (2) In the poor prognosis group, power values of δ brain waves in leads Fp1-2, F4, C4, P4, F8, and T4 were higher than those in the good prognosis group (87.99(41.57,196.69) to 50.67(26.64,54.75), Z=2.76, P=0.006); (79.17(40.71,200.00) to 45.06(20.22,61.00), Z=2.10, P=0.036); (72.64(34.97,219.78) to 34.42(19.81,63.4), Z=2.03, P=0.043); (65.06(33.36,177.45) to 28.12(15.88,63.36), Z=2.08, P=0.038); (52.92(25.64,187.91) to 23.61(11.67,43.26), Z=2.21, P=0.027); (66.67(32.56,180.76) to 36.31(17.2,53.78), Z=2.46, P=0.014); (57.30(25.24,127.04) to 29.57(11.91,41.89), Z=2.26, P=0.024). Power values of θ brain waves in leads Fp1-2, F3, F4, C3, C4, P3-4, O1, F7-8, and T3-4 were higher in the poor prognosis group(77.45(47.63,138.72)比35.88(20.92,44.81), Z=3.50, P<0.001); (77.05(35.16,120.22) to 38.74(19.86,58.09), Z=2.27, P=0.023); (85.24(52.53,147.90) to 35.42(14.7,52.59), Z=2.61, P=0.009); (75.81(37.90,124.97) to 36.85(17.92,55.43), Z=2.30, P=0.021); (72.00(43.92,123.54) to 28.37(14.02,51.9), Z=2.22, P=0.027); (67.08(32.01,104.05) to 31.32(17.98,45.28), Z=2.10, P=0.035); (55.33(32.29,94.30) to 25.64(11.87,34.01), Z=2.24, P=0.025); (48.84(20.64,96.28) to 19.85(9.83,28.58), Z=2.30, P=0.022);(48.46(25.06,81.78) to 23.95(8.80,29.16), Z=2.51, P=0.012); (64.46(39.38,112.44) to 26.85(15.74,39.58), Z=2.80, P=0.005); (65.68(31.78,102.00) to 31.09(15.98,46.96), Z=2.38, P=0.017); (45.26(28.34,73.14) to 21.45(10.57,36.59), Z=2.04, P=0.042); (43.50(22.58,78.67) to 25.45(11.91,32.26), Z=2.22, P=0.027). Power values of slow-wave index in leads Fp1-2, F3-4, C3-4, P4, F7-8, and T4, as well as the overall brain average, were higher in the poor prognosis group (6.64(2.98,10.42) to 3.65(2.31,4.30), Z=2.65, P=0.01); (6.53(3.96,11.65) to 3.53(2.56,4.51), Z=2.30, P=0.022); (7.38(4.62,13.12) to 3.83(1.70,4.71), Z=2.38, P=0.017); (5.88(4.02,12.15) to 3.18(2.21,4.46), Z=2.29, P=0.022); (6.13(3.83,11.22) to 2.97(1.53,4.58), Z=2.01, P=0.044); (6.07(3.53,9.39) to 2.74(2.00,3.81), Z=2.40, P=0.016);(4.11(2.51,9.23) to 2.18(1.37,2.82), Z=2.25, P=0.024); (5.71(3.81,10.44) to 3.22(1.86,4.04), Z=2.28, P=0.023); (6.00(3.65,10.37) to 3.04(2.00,4.00), Z=2.39, P=0.017); (4.08(2.56,8.33) to 2.08(1.60,3.14), Z=2.50, P=0.013), with significant statistical differences noted (5.45(3.31,10.08) to 3.17(2.02,4.88), Z=3.62, P=0.005). (3) Logistic regression results showed that admission homocysteine levels ( OR 1.311,95% CI 1.008-1.705, P=0.044), admission NIHSS scores ( OR 1.588,95% CI 1.074-2.349, P=0.020), and overall brain average slow-wave index were influencing factors for poor prognosis in cerebral hemorrhage ( OR 8.596,95% CI 1.088-67.889, P=0.041). (4) ROC curve analysis revealed that the AUC for predicting adverse outcomes in cerebral hemorrhage was 0.768 (95% CI (0.665, 0.872)) for admission homocysteine levels, 0.743 (95% CI (0.634, 0.852)) for the overall brain average slow-wave index, and 0.896 (95% CI (0.827, 0.965)) for admission NIHSS. The cutoff values were 15.67, 3.62, and 8.5, respectively. Sensitivity was 77.8%, 71.1%, and 68.9%, and specificity was 59.4%, 68.7%, and 100%, respectively. The Youden indices were 0.372, 0.398, and 0.689. Conclusion:In the acute phase of cerebral hemorrhage, electroencephalographic physiological changes manifest shows an increase in the δ, θ, and slow-wave index throughout the entire brain. Higher admission homocysteine levels suggest a worse prognosis in patients with cerebral hemorrhage. Admission homocysteine levels and overall brain average slow-wave index have certain predictive value for adverse outcomes in acute cerebral hemorrhage.
9.Association of psychological stress with wives’ hypertension across over 10 million Chinese married female population aged 20-49 years
Zhenyan ZHAO ; Jiajing JIA ; Xinyi LYU ; Lihua ZHANG ; Yuanyuan WANG ; Yuan HE ; Zuoqi PENG ; Ya ZHANG ; Hongguang ZHANG ; Qiaomei WANG ; Haiping SHEN ; Yiping ZHANG ; Donghai YAN ; Xu MA ; Ying YANG
Chinese Medical Journal 2024;137(13):1583-1591
Background::Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women.Methods::Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.Results::Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women ( Pfor trend <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25-1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20-1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives’ hypertension, with adjusted ORs of 1.28 (95% CI: 1.25-1.31), 1.19 (95% CI: 1.17-1.21), and 1.28 (95% CI: 1.26-1.31), respectively. Conclusion::Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.
10.Research progress on nursing-sensitive quality indicators for acute poisoning patients
Ying LI ; Jing WEI ; Hua XU ; Ya ZHANG ; Xiangguang YIN ; Mingjie ZHAO ; Jing WANG
Chinese Journal of Modern Nursing 2024;30(30):4191-4196
This article provides a review of domestic and international research on nursing-sensitive quality indicators (NSQIs) and evaluation systems for acute poisoning patients. It organizes the indicators into three dimensions based on the "structure-process-outcome" framework. The need for establishing a unified, comprehensive, and nationally suitable system of NSQIs in China is emphasized to standardize nursing practices and improve the monitoring of care quality. Although existing indicators possess some scientific validity, they often overlap with emergency nursing quality evaluation systems or are limited to specific types of poisoning. In addition, large-scale clinical trials to test their practical application and accessibility have yet to be conducted. This review aims to consolidate and analyze NSQIs for acute poisoning patients and provide a foundation and reference for improving the quality of nursing care for these patients.

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