1.Effect of PDCA cycle on improving the completion rate of sepsis bundle treatment
Xiaoming SANG ; Yuli LI ; Yuping HAN ; Na LI ; Zhenmei ZHANG ; Fei WANG
Chinese Journal of Practical Nursing 2024;40(21):1614-1620
Objective:To analyze the effect of analysis plan, do, check, and action (PDCA) cycle in improving the completion rate of sepsis bundle treatment in sepsis patients and the knowledge-attitude-practice of sepsis bundle treatment in medical staff.Methods:Using the historical control method, sepsis patients admitted to the Emergency Trauma Intensive Care Unit of Shandong Provincial Hospital Affiliated to Shandong First Medical University were selected as the research objects by convenience sampling. The 35 patients admitted from January to December 2021 will be included in the control group; from June 2022 to June 2023, 28 patients were admitted to the observation group. The control group received routine nursing care, while the observation group received intervention based on the PDCA cycle. The completion rate of sepsis bundle treatment before and after PDCA cycle implementation was compared. The 27 nurses and 5 doctors working in trauma care unit were investigated by using a self-designed questionnaire on their knowledge and practice level of sepsis bundle treatment. The completion rate of sepsis bundle treatment before and after the implementation of PDCA cycle was compared.Results:The control group included 19 males and 16 females, aged (61.77 ± 8.64) years. The observation group included 13 males and 15 females, aged (60.61 ± 10.20) years. After the implementation of PDCA cycle, the completion rate of 3h bundle treatment for sepsis in the observation group was 89.29% (25/28), which was higher than 31.42% (10/35) in the control group, with a statistically significant difference ( χ2=23.22, P<0.05). The completion rate of sepsis bundle treatment within 6 hours in the observation group was 11/11, which was higher than 5/9 in the control group, with a statistically significant difference ( χ2=6.11, P<0.05). Moreover, after the implementation of PDCA cycle, the total score and sub-scale scores of the knowledge-attitude-practice among medical staffs increased from 86.60 ± 10.33, 21.00 ± 4.74, 18.00 ± 1.58, and 47.60 ± 4.10 to 100.00 ± 5.20, 27.60 ± 2.51, 19.60 ± 0.55, and 52.80 ± 2.28 respectively, with statistically significant differences ( t values were -5.10 - -3.14, all P<0.05). Conclusions:PDCA cycle can improve the completion rate of sepsis bundle treatment and improve the level of knowledge, attitude and practice of medical staff.
2.Relationship between serum miR-326 and miR-623 expression and clinical pathological characteristics in non-small cell lung cancer patients
Rujing HUANG ; Hongling LU ; Chao WU ; Hongjuan YANG ; Xiaoming YIN ; Yang ZHAO ; Huawei KANG ; Fei TIAN ; Yunchuan SUN
Journal of Clinical Surgery 2024;32(7):706-710
Objective To investigate the relationship between the expression of serum microRNA-326(miR-326)and microRNA-623(miR-623)in non-small cell lung cancer(NSCLC)patients and their clinical pathological characteristics and prognosis.Methods A total of 114 NSCLC patients diagnosed in our hospital from March 2019 to June 2020 were collected as study subjects as case group,123 healthy individuals who underwent physical examination were as the control group.According to the 3-year prognosis,patients were separated into a survival group of 71 cases and a death group of 43 cases.Patient related clinical data were collected,real-time fluorescence quantitative PCR method was applied to detect the expression levels of miR-326 and miR-623 in various serum samples;Kaplan-Meier method was applied to analyze the relationship between the expression levels of serum miR-326 and miR-623 in NSCLC patients and their 3-year prognosis;Cox proportional risk regression model was applied to analyze the influencing factors of 3-year prognosis in NSCLC patients.Results The expression levels of serum miR-326 in the case group and control group were 0.64±0.15 and 1.02±0.23,respectively,and the expression levels of miR-623 were 0.56±0.10 and 0.98±0.15,respectively.The difference between the two groups was statistically significant(P<0.05).The proportions of patients with low expression of miR-326 and miR-623 in low differentiation,TNM stage Ⅲ+Ⅳ,and lymph node metastasis were higher than those in high differentiation,TNM stage Ⅰ and Ⅱ,and no lymph node metastasis(P<0.05).The 3-year survival rates of patients with low expression of miR-326(20/55,36.36%)and miR-623(27/61,44.26%)in the serum of NSCLC patients were lower than those of patients with high expression of miR-326(51/59,86.44%)and miR-623(44/53,83.02%)(Log Rank x2=32.060,22.812,P<0.05).Serum miR-326[(0.55±0.09)vs.(0.69±0.11)]and miR-623 levels[(0.48±0.08)vs.(0.61±0.10)]of patients in the death group were significantly lower than those in the survival group(P<0.05).The area under the curve(AUC)for poor prognosis of serum miR-326 and miR-623 alone and in combination in patients diagnosed with NSCLC were 0.828(95%CI:0.754 to 0.901),0.763(95%CI:0.671 to 0.855),and 0.903(95%CI:0.849 to 0.958),respectively.The proportions of patients with TNM stage Ⅲ+Ⅳ,lymph node metastasis,low expression of miR-326 and low expression of miR-623in the death group were higher than those in the survival group(P<0.05).MiR-326 and miR-623 were protective factors affecting 3-year mortality in NSCLC patients,while TNM staging and lymph node metastasis were independent risk factors affecting 3-year mortality in NSCLC patients(P<0.05).Conclusion The low expression of miR-326 and miR-623 may be involved in the occurrence and development of lung cancer,which is closely related to the clinical pathological characteristics and poor prognosis of patients.
3.Comparison of mid-to-long term outcomes between mitral valve repair and biological valve replacement in patients over 60 with rheumatic mitral valve disease based on a propensity score matching study
Wenbo ZHANG ; Jie HAN ; Tiange LUO ; Baiyu TIAN ; Fei MENG ; Wenjian JIANG ; Yuqing JIAO ; Xiaoming LI ; Jintao FU ; Yichen ZHAO ; Fei LI ; Xu MENG ; Jiangang WANG
Chinese Journal of Surgery 2024;62(11):1016-1023
Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.
4.Comparison of mid-to-long term outcomes between mitral valve repair and biological valve replacement in patients over 60 with rheumatic mitral valve disease based on a propensity score matching study
Wenbo ZHANG ; Jie HAN ; Tiange LUO ; Baiyu TIAN ; Fei MENG ; Wenjian JIANG ; Yuqing JIAO ; Xiaoming LI ; Jintao FU ; Yichen ZHAO ; Fei LI ; Xu MENG ; Jiangang WANG
Chinese Journal of Surgery 2024;62(11):1016-1023
Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.
5.A clinical study on the treatment of relapsed/refractory acute myeloid leukemia with venetoclax regimen
Lei FANG ; Fei XIAOMING ; Yang YUANLIN ; Ji YANPING ; Yu XIANQIU ; Tang YU
Chinese Journal of Clinical Oncology 2024;51(7):348-353
Objective:To explored the feasibility and efficacy of a rapid ramp-up,2-week maximum regimen of venetoclax(VEN)plus low-dose cytarabine(LDAC)for treating relapsed/refractory acute myeloid leukemia(R/R AML).Methods:We retrospectively analyzed patients with venetoclax-na?ve R/R AML treated with VEN+LDAC between October 2018 and November 2023.On the first day,patients received 200 mg of VEN,and the dose was quickly increased to 400 mg for the rest of the treatment;cytarabine was administered subcutaneously at a low dose of 20 mg/m2/day.The treatment duration was 10 or 14 days,depending on the condition of bone marrow hyperplasia determined on the 8th day of treatment.No patients received venetoclax monotherapy.All patients responding to salvage therapy received VEN+LDAC until disease progression or transplantation.Results:Among the patients,the median follow-up duration was 27.5 months.No clinical mani-festations of tumor lysis syndrome(TLS)occurred during the treatment.The overall response rate(ORR)was 68.75%,including four com-plete responses(CR),one complete remission with incomplete hematologic recovery(CRi),and six partial responses(PR).The median num-ber of best treatment result cycles was one cycle.The median overall survival(OS)in the whole cohort was 5.8(0.5-47.2)months;the medi-an progression-free survival(PFS)was 22.2(7.3-42.9)months.The major adverse events were grade 3-4 hematologic adverse events and in-fections.Conclusions:The 8th-day myelosuppression-adjusted VEN+LDAC regimen is a feasible salvage option with a reasonable safety pro-file in patients with venetoclax-na?ve R/R AML.Most patients tolerated the 14-day treatment;the response was generally rapid in the re-sponding patients.
6.Path analysis of medical narrative competence and profession quality of life on professional identity of nurses
Jinjin PAN ; Yuping HAN ; Na LI ; Xiaoli LIU ; Fei WANG ; Xiaoming SANG
Chinese Journal of Practical Nursing 2023;39(34):2694-2700
Objective:To explore the path relationship among medical narrative competence and profession quality of life on professional identity of nurses, so as to provide reference for improving nurses ′professional identity. Methods:This study was across-sectional survey. From October 2022 to February 2023, totally 619 nurses in Shandong Provincial Hospital Affiliated to Shandong First Medical University were investigated using Self-designed Demographic Questionnaire, Medical Narrative Competence Scale, Professional Quality of Life Scale and Professional Identity Scale.Results:The score of nurses ′s medical narrative competence was (144.13 ± 22.09) points, compassion satisfaction was (34.82 ± 6.96) points, job burnout was (24.03 ± 5.48) points, secondary traumatic stress was (23.91 ± 5.89) points, and the scores of nurses ′ professional identity was (112.68 ± 19.05) points. Nurses ′ medical narrative competence was positively correlated with compassion satisfaction and professional identity ( r=0.585, 0.697, both P<0.01); nurses ′ medical narrative competence was negatively correlated with job burnout and secondary traumatic stress ( r=-0.516, -0.214, both P<0.01). Regression analysis showed that nurses ′ medical narrative ability, compassion satisfaction and job burnout were the influencing factors of nurses ′professional identity ( t=13.26, 10.52, -2.32, all P<0.05). Structural equation model indicated that medical narrative ability of nurses had an intermediary effect on professional identity through the dimension of compassion satisfaction, and the intermediary effect was 0.269, and the intermediary effect accounted for 36.88% of the total effect. Conclusions:Medical narrative ability of nurses can have positive emotional experience on nurses ′ psychology, and thus have an impact on professional identity. Nursing managers should pay attention to the level of nurses ′ medical satisfaction, and give full play to the intermediary effect of compassion satisfaction in nurses ′ medical narrative ability and professional identity.
7.Clinical value of CT-based three-section formula in identification of Siewert types of adeno-carcinoma of esophagogastric junction
Yiting LIU ; Xiaoming LI ; Xiaoting LI ; Jiazheng LI ; Meng HE ; Fei SHAN ; Ping CAI ; Ziyu LI ; Lei TANG
Chinese Journal of Digestive Surgery 2022;21(1):135-142
Objective:To investigate the clinical value of computer tomography (CT)-based three-section formula in identification of Siewert types of adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 62 AEG patients who were admitted to two medical centers, including 33 patients from Peking University Cancer Hospital and 29 patients from the First Affiliated Hospital of Amy Medical University, between January 2019 and January 2021 were collected. There were 53 males and 9 females, aged (66±9)years. All patients underwent CT examination to obtain the coronal and axial images and determine the upper and lower edges of the tumor and the esophagogastric junction, which were imported into the formula for Siewert classification. Observation indicators: (1) results of CT examination and pathological examination; (2) consistence of judgements for CT examination between doctors; (3) consistence of judgements between CT examination and patholo-gical examination. Results of pathological examination came from intraoperative surgical observa-tion and postoperative histopathological examination. Measurement data with normal distribution were represented as Mean± SD, and count data were described as absolute numbers or percentages. The consistency coefficient Kappa ( κ) was used to evaluate the consistency of diagnosis between resear-chers. The κ≥0.75 was regarded as excellent consistency, 0.40< κ<0.75 as good consistency, κ ≤0.40 as poor consistency. Wilcoxon rank sum test was used to evaluate the statistical difference between results of the CT-based three-section formula method and the pathological examination. Taking the results of histopathological examination as standard, the sensitivity, specifi-city, accuracy and 95% confidence interval of the CT-based three-section formula method were calculated. Results:(1) Results of CT examination and pathological examination: all the 62 patients underwent CT examination successfully to obtain the coronal and axial images and determine the upper and lower edges of the tumor and the esophagogastric junction, which were used for Siewert classifica-tion. There were 3 cases with AEG of Siewert type Ⅰ, 47 cases with AEG of Siewert type Ⅱ and 12 cases with AEG of Siewert type Ⅲ according to doctor's judgement from the Peking University Cancer Hospital, and there were 3 cases with AEG of Siewert type Ⅰ, 49 cases with AEG of Siewert type Ⅱ and 10 cases with AEG of Siewert type Ⅲ according to doctor's judgement from the First Affiliated Hospital of Amy Medical University, respectively. After arbitration, there were 2 cases with AEG of Siewert type Ⅰ, 48 cases with AEG of Siewert type Ⅱ and 12 cases with AEG of Siewert type Ⅲ determined by the CT based three-section formula. There were 7 cases of stage T1, 10 cases of stage T2, 24 cases of stage T3, 14 of stage T4a and 7 cases of stage T4b of pathological T staging. There were 2 cases with AEG of Siewert type Ⅰ, 48 cases with AEG of Siewert type Ⅱ and 12 cases with AEG of Siewert type Ⅲ determined by pathological examination. (2) Consistence of judgements for CT examination between doctors: the consistency of Siewert classification determined by CT-based three-section formula between 2 doctors was good ( κ=0.74, P<0.001). (3) Consistence of judgements between pathological examination and CT examination: with Siewert classification determined by pathological examination as reference, the accuracy of Siewert classification determined by CT based three-section formula was 90.3%( κ=0.73, P<0.001). The sensitivity and specificity of CT-based three-section formula were 66.7%(95% confidence interval as 20.8%-93.9%) and 100.0%(95% confidence interval as 93.9%-100.0%) for AEG of Siewert type Ⅰ, 97.7%(95% confidence interval as 88.2%-99.6%) and 72.2%(95% confidence interval as 49.1%-87.5%) for AEG of Siewert type Ⅱ, 73.3%(95% confidence interval as 48.0%-89.1%) and 97.9%(95% confidence interval as 88.9%-99.9%) for AEG of Siewert type Ⅲ, respectively. Conclusion:The CT-based three-section formula can be used for identification of Siewert types of AEG, with a high accuracy.
8.Optimization strategy of anaesthesia for laparoscopic gynecological surgery: anterior quadratus lumborum block at supra-arcuate ligament combined with general anesthesia
Liping WANG ; Sheng QIU ; Jinmei GAO ; Fei YANG ; Yiqing ZOU ; Xiaoming GUO
Chinese Journal of Anesthesiology 2022;42(5):581-585
Objective:To evaluate the optimization efficacy of anterior quadratus lumborum block at supra-arcuate ligament (SA-AQLB) combined with general anesthesia for laparoscopic gynecological surgery.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 28-64 yr, weighing 52-78 kg, with height of 154-166 cm, scheduled for elective laparoscopic gynecological surgery, were divided into general anesthesia group (group G, n=40) and SA-AQLB combined with general anesthesia group (group SG, n=40) using a random number table method.In group SG, bilateral SA-AQLB was performed under ultrasound guidance before anesthesia induction, and 0.4% ropivacaine 25 ml plus dexamethasone 5 mg was injected into both sides.Combined intravenous-inhalational anesthesia was applied in both groups.Patient-controlled intravenous analgesia (PCIA) with sufentanil 2 μg/kg (in 150 ml of normal saline) was performed after surgery.The PCIA pump was set up to deliver a 2 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.Visual analogue scale (VAS) scores for abdomen, pelvis and shoulder pain were recorded at 1, 6, 12, 24 and 48 h after operation.Flurbiprofen was used for rescue analgesia when VAS score >4.The occurrence of intraoperative cardiovascular events and amount of sufentanil used during operation were recorded.The time to first pressing the analgesia pump, effective pressing times of PCA, requirement for rescue analgesia and consumption of sufentanil after operation were recorded.The extubation time, time to first flatus after operation, first ambulation time, length of hospital stay and development of postoperative adverse reactions such as nausea and vomiting, urinary retention and respiratory depression within 48 h after operation were recorded. Results:Compared with group G, the incidence of intraoperative hypertension and tachycardia was significantly decreased, the incidence of intraoperative hypotension and bradycardia was increased, the intraoperative consumption of sufentanil was reduced, the extubation time was shortened, the time to first pressing the analgesia pump was prolonged, the effective pressing times of PCA, requirement for rescue analgesia and postoperative consumption of sufentanil were reduced, the time to first flatus, first ambulation time and length of hospital stay were shortened, VAS scores for abdomen, pelvis and shoulder pain were decreased at each time point after operation, and the incidence of nausea and vomiting, urinary retention and respiratory depression after operation was decreased in group SG ( P<0.01). Conclusions:Compared with general anesthesia, the combination of SA-AQLB and general anesthesia can reduce the opioid consumption, inhibit intraoperative stress responses and postoperative hyperalgesia and promote early postoperative recovery when used for the patients undergoing laparoscopic gynecological surgery.
9.Analysis of therapeutic effect and influencing factors of radiofrequency ablation for colorectal cancer liver metastases
Fei ZHOU ; Xiaoming YANG ; Shufeng XU ; Hongjie FAN
Chinese Journal of Radiology 2022;56(2):188-195
Objective:To explore the efficacy and influencing factors of radiofrequency ablation (RFA) in the treatment of colorectal cancer liver metastases (CRLM).Methods:The clinical and imaging data of 281 patients (477 intrahepatic metastatic tumors) who received percutaneous RFA treatment in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from December 2009 to December 2020 were retrospectively analyzed. Factors that may affect the efficacy of RFA were recorded, including carcinoembryonic antigen (CEA), differentiation, extrahepatic metastasis, tumor location and size, complications and other information. Patients were followed up through hospital admissions, telephone, etc. The primary endpoints were overall survival (OS) and local tumor progression-free survival (LTPFS). Univariate and multivariate logistic regression models were used to identify predictors of residual tumor. Univariate and multivariate Cox proportional hazards regression were used to identify the influencing factors of LTPFS and OS. The median LTPFS and OS were estimated by the Kaplan-Meier curve and compared by the log-rank test.Results:After RFA, 68 (14.3%) tumor residues were observed. Multivariate logistic regression showed that the risk factors for residual tumor were size ≥20 mm, high-risk and perivascular location, and minimal ablative margin<5 mm. During the follow-up period, the main complication rate was 4.3% (12/281) and the fatality rate was 31.3% (88/281). At the same time, local tumor progression was found in 167 (35.0%) lesions post-RFA. The median time of LTPFS and OS estimated by the Kaplan Meier method were 35.0 (95%CI 26.53-43.48) and 44.0 (95%CI 29.70-58.30) months, respectively. The cumulative proportion of LTPFS and OS were 37.2% and 40.4% respectively in the 5th year. Multivariate Cox proportional hazard regression showed that CEA≥30 ng/ml, tumor size ≥20 mm, and minimal ablative margin<5 mm were risk factors for LTPFS; extrahepatic metastasis, tumor burden>30 mm, and lesion with minimal ablative margin<5 mm were independent risk factors for OS; re-intervention was an independent protective factor for OS.Conclusions:Adequate ablative margin and less tumor burden were beneficial to local tumor control and long-term survival of patients in the RFA treatment; the existence of extrahepatic metastasis was an important risk factor for OS, and re-interventional therapy was beneficial to extend OS.
10.KAT8/MOF-Mediated Anti-Cancer Mechanism of Gemcitabine in Human Bladder Cancer Cells
Huihui ZHU ; Yong WANG ; Tao WEI ; Xiaoming ZHAO ; Fuqiang LI ; Yana LI ; Fei WANG ; Yong CAI ; Jingji JIN
Biomolecules & Therapeutics 2021;29(2):184-194
Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell ® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.

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