Objective:To investigate the prognostic value of aldosterone synthase (CYP11B2) immunohistochemical expression in adrenal specimens for surgical outcomes of primary aldosteronism (PA).Methods:The clinical data of 99 patients who underwent total unilateral adrenalectomy from June 2022 to January 2023 at Beijing Anzhen Hospital was retrospectively analysed. The clinical data of 99 patients who underwent unilateral total adrenalectomy at Beijing Anzhen Hospital from June 2022 to January 2023 were retrospectively analyzed.There were 59 patients in the PA group, age (53.02±10.56) years, body mass index (BMI) (26.28±4.33) kg/m 2, preoperative aldosterone 29.0(15.9, 61.5)ng/dl, plasma renin 1.3(0.6, 2.8)μIU/ml, aldosterone renin ratio (ARR) 19.3(9.1, 59.2) μg/μIU, preoperative potassium (3.60±0.69) mmol/L, and systolic blood pressure (156.54±21.39) mmHg (1 mmHg=0.133 kPa).There were 40 cases in the nonfunctioning adenoma (NFA) group, age (57.23±9.39) years, BMI (27.07±3.46) kg/m 2, preoperative aldosterone 9.0(7.2, 14.1) ng/dl, plasma renin 18.0(5.2, 47.6)μIU/ml, ARR 0.6(0.2, 1.4) μg/μIU, preoperative potassium (4.17±0.41) mmol/L, and systolic blood pressure (157.97±26.87) mmHg. The differences between the two groups were statistically significant for potassium ( P<0.01), aldosterone ( P=0.012), renin ( P<0.01), and ARR ( P<0.01).Surgical outcomes were assessed using the Consensus on the Outcome of Surgery for Primary Aldosteronism (PASO) (complete/partial/no success for clinical and biochemical outcomes). CYP11B2 expression was evaluated by immunohistochemistry using the 2022 World Health Organization's histopathology of primary aldosteronism (HISTALDO) criteria. The correlation between the expression of CYP11B2 and surgical outcomes was assessed. Results:The mean follow-up of 99 patients was (11.73±4.92) months. Of these, 36 out of 59 PA patients had positive CYP11B2 expression in their adrenal specimens, while 23 were negative; all 40 NFA patients were negative for CYP11B2. Among the 36 CYP11B2-positive PA patients, there were 19 cases of aldosterone-producing adenomas, 3 aldosterone-producing nodules, 4 aldosterone-producing micronodules, 8 multiple aldosterone-producing micronodules, and 2 aldosterone-producing diffuse hyperplasia. 36 cases of CYP11B2-positive PA patients had complete clinical success in 15 cases, partial success in 20 cases, and no success in 1 case, and complete biochemical success in 24 cases, partial success in 11 cases, and no success in 1 case; 23 CYP11B2-negative PA patients had complete clinical success in 4 cases, partial success in 15 cases, and no success in 4 cases, and complete biochemical success in 6 cases, partial success in 15 cases, and no success in 2 cases. Adrenal specimens from CYP11B2-positive PA patients had significantly better clinical ( P=0.038) and biochemical ( P=0.008) success rates than CYP11B2-negative PA patients. Patients with aldosterone-producing adenomas had complete clinical success in 8 cases, partial success in 11 cases, and no success in 0 cases, and biochemical success was completely achieved in 16 cases, partially achieved in 2 cases, and not successful in 1 case. They also had significantly higher clinical ( P=0.028) and biochemical ( P<0.01) success rates compared to CYP11B2-negative PA patients. Conclusions:Patients with PA who had immunohistochemical staining for CYP11B2 positivity and high expression in adrenal specimens had a better postoperative clinical and biochemical prognosis. Patients with aldosterone-producing adenomas had the greatest postoperative outcome of all pathological subtypes of PA.

Objective:To explore the risk factors of adverse events during the perioperative period of transurethral resection of bladder tumor(TURBT)in bladder cancer patients with coronary atherosclerotic heart disease(CAD).Methods:We retrospectively analyzed the clinical data of bladder cancer patients who underwent TURBT in Beijing Anzhen Hospital from June 2022 to September 2024.All patients with bladder cancer and CAD underwent coronary computed tomography angiography(CCTA)for diagnosis and assessment of CAD before surgery.Based on the CCTA results,the patients with bladder cancer and CAD were divided into two groups:those with mild to moderate coronary stenosis and those with severe coronary stenosis.The severe coronary stenosis group was further divided into two subgroups based on whether they received low-molecular-weight heparin(LMWH)bridging therapy or continued their anti-platelet treatment before surgery.Perioperative anticoagulation and antiplatelet strategies were adjusted according to the opinions of the specialists.The incidence of adverse events within 30 days postoperative-ly was followed up and analyzed.Results:A total of 80 bladder cancer patients with CAD who underwent TURBT were included in the study.Among the 80 patients with CAD,55(68.8％)had mild to moder-ate coronary stenosis,and 25(31.2％)had severe coronary stenosis.Compared with those had mild to moderate coronary stenosis,the patients who had severe coronary stenosis had a higher incidence of post-operative bleeding and pulmonary embolism,although the differences were not statistically significant(P＞0.05).However,the incidence of postoperative myocardial infarction was significantly higher in the patients who had severe coronary stenosis(P=0.034).Among the patients with severe coronary stenosis,8(32.0％)received LMWH bridging therapy before TURBT,and 17(68.0％)continued their previous antiplatelet treatment.Compared with those who continued antiplatelet treatment,the patients who re-ceived LMWH bridging therapy had a higher incidence of postoperative bleeding and pulmonary embo-lism,although the differences were not statistically significant(P＞0.05).However,the incidence of postoperative myocardial infarction was significantly higher in the LMWH bridging group(P=0.032).Conclusion:Patients with mild-to-moderate coronary stenosis demonstrate relatively low perioperative risk during TURBT procedures and may safely undergo TURBT following antiplatelet therapy discontinuation.Conversely,those with severe coronary stenosis exhibit significantly higher perioperative risk and require intensive monitoring.In bladder cancer patients with concomitant severe coronary stenosis,perioperative LMWH bridging therapy is associated with increased myocardial infarction risk,whereas continued anti-platelet therapy does not elevate postoperative bleeding risk.Current evidence therefore supports maintai-ning antiplatelet therapy in these patients,with appropriate bleeding risk assessment.

OBJECTIVE: To observe the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on learning-memory ability and hippocampal mammalian sterile 20-like kinase 1 (Mst1)/nuclear factor κB (NF-κB) p65 pathway related to inflammatory response in rats with vascular dementia (VD). METHODS: A total of 60 male Wistar rats of SPF grade were randomly divided into a sham operation group (12 rats) and a modeling group (48 rats). VD model was established by the method of modified bilateral common carotid artery permanent ligation in the modeling group. Thirty-six rats with successful modeling were randomly divided into a model group, a moxibustion group and a western medication group, with 12 rats in each group. Huayu Tongluo moxibustion was applied at "Dazhui" (GV14), "Baihui" (GV20) and "Shenting" (GV24) in the moxibustion group, 20 min each time, once a day, 7 day-intervention was as one course, and 1 day-interval was taken between two courses, for a total of 3 courses. In the western medication group, piracetam was given 0.72 mg/kg by intragastric administration, twice a day, the course of intervention was same as that of the moxibustion group. The learning-memory ability was detected by Morris water maze test; the morphology of hippocampal CA1 region was observed by HE staining; the mRNA expression of Mst1, M1 microglia markers CD86, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected by real-time PCR; the levels of IL-6 and TNF-α in hippocampus were detected by ELISA; and the protein expression of Mst1 and NF-κB p65 in hippocampus was detected by Western blot in rats of each group. RESULTS: Compared with the sham operation group, the escape latency was prolonged in the model group (P<0.05); compared with the model group, the escape latency was shortened in the moxibustion group and the western medication group (P<0.05). The cells in the CA1 region of hippocampus were disordered, cell collapse and irregular nuclei could be observed in the model group; compared with the model group, the cell arrangement in the CA1 region of hippocampus was more regular, and the damage was improved in the moxibustion group and the western medication group. Compared with the sham operation group, the mRNA expression of Mst1, CD86, IL-6 and TNF-α, as well as the protein expression of Mst1, NF-κB p65 in hippocampus were increased in the model group (P<0.05). Compared with the model group, the mRNA expression of Mst1, CD86, IL-6 and TNF-α, as well as the protein expression of Mst1, NF-κB p65 in hippocampus were decreased in the moxibustion group and the western medication group (P<0.05). Compared with the sham operation group, the levels of IL-6 and TNF-α in hippocampus were increased in the model group (P<0.05). Compared with the model group, the levels of IL-6 and TNF-α in hippocampus were decreased in the moxibustion group and the western medication group (P<0.05). CONCLUSION Huayu Tongluo moxibustion can improve the learning-memory ability of VD rats, the mechanism may be related to regulating the activation of microglia through Mst1/NF-κB p65 pathway, reducing the release of pro-inflammatory factors i.e. IL-6 and TNF-α, so as to alleviating the damage of inflammatory factors in the hippocampus of VD rats.
Animals ; Male ; Rats ; Moxibustion ; Hippocampus/metabolism* ; Rats, Wistar ; Dementia, Vascular/genetics* ; Memory/drug effects* ; Humans ; Transcription Factor RelA/genetics* ; Learning ; Protein Serine-Threonine Kinases/genetics* ; Acupuncture Points ; Interleukin-6/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal

Objective:To explore the risk factors of adverse events during the perioperative period of transurethral resection of bladder tumor(TURBT)in bladder cancer patients with coronary atherosclerotic heart disease(CAD).Methods:We retrospectively analyzed the clinical data of bladder cancer patients who underwent TURBT in Beijing Anzhen Hospital from June 2022 to September 2024.All patients with bladder cancer and CAD underwent coronary computed tomography angiography(CCTA)for diagnosis and assessment of CAD before surgery.Based on the CCTA results,the patients with bladder cancer and CAD were divided into two groups:those with mild to moderate coronary stenosis and those with severe coronary stenosis.The severe coronary stenosis group was further divided into two subgroups based on whether they received low-molecular-weight heparin(LMWH)bridging therapy or continued their anti-platelet treatment before surgery.Perioperative anticoagulation and antiplatelet strategies were adjusted according to the opinions of the specialists.The incidence of adverse events within 30 days postoperative-ly was followed up and analyzed.Results:A total of 80 bladder cancer patients with CAD who underwent TURBT were included in the study.Among the 80 patients with CAD,55(68.8％)had mild to moder-ate coronary stenosis,and 25(31.2％)had severe coronary stenosis.Compared with those had mild to moderate coronary stenosis,the patients who had severe coronary stenosis had a higher incidence of post-operative bleeding and pulmonary embolism,although the differences were not statistically significant(P＞0.05).However,the incidence of postoperative myocardial infarction was significantly higher in the patients who had severe coronary stenosis(P=0.034).Among the patients with severe coronary stenosis,8(32.0％)received LMWH bridging therapy before TURBT,and 17(68.0％)continued their previous antiplatelet treatment.Compared with those who continued antiplatelet treatment,the patients who re-ceived LMWH bridging therapy had a higher incidence of postoperative bleeding and pulmonary embo-lism,although the differences were not statistically significant(P＞0.05).However,the incidence of postoperative myocardial infarction was significantly higher in the LMWH bridging group(P=0.032).Conclusion:Patients with mild-to-moderate coronary stenosis demonstrate relatively low perioperative risk during TURBT procedures and may safely undergo TURBT following antiplatelet therapy discontinuation.Conversely,those with severe coronary stenosis exhibit significantly higher perioperative risk and require intensive monitoring.In bladder cancer patients with concomitant severe coronary stenosis,perioperative LMWH bridging therapy is associated with increased myocardial infarction risk,whereas continued anti-platelet therapy does not elevate postoperative bleeding risk.Current evidence therefore supports maintai-ning antiplatelet therapy in these patients,with appropriate bleeding risk assessment.

Objective:To investigate the prognostic value of aldosterone synthase (CYP11B2) immunohistochemical expression in adrenal specimens for surgical outcomes of primary aldosteronism (PA).Methods:The clinical data of 99 patients who underwent total unilateral adrenalectomy from June 2022 to January 2023 at Beijing Anzhen Hospital was retrospectively analysed. The clinical data of 99 patients who underwent unilateral total adrenalectomy at Beijing Anzhen Hospital from June 2022 to January 2023 were retrospectively analyzed.There were 59 patients in the PA group, age (53.02±10.56) years, body mass index (BMI) (26.28±4.33) kg/m 2, preoperative aldosterone 29.0(15.9, 61.5)ng/dl, plasma renin 1.3(0.6, 2.8)μIU/ml, aldosterone renin ratio (ARR) 19.3(9.1, 59.2) μg/μIU, preoperative potassium (3.60±0.69) mmol/L, and systolic blood pressure (156.54±21.39) mmHg (1 mmHg=0.133 kPa).There were 40 cases in the nonfunctioning adenoma (NFA) group, age (57.23±9.39) years, BMI (27.07±3.46) kg/m 2, preoperative aldosterone 9.0(7.2, 14.1) ng/dl, plasma renin 18.0(5.2, 47.6)μIU/ml, ARR 0.6(0.2, 1.4) μg/μIU, preoperative potassium (4.17±0.41) mmol/L, and systolic blood pressure (157.97±26.87) mmHg. The differences between the two groups were statistically significant for potassium ( P<0.01), aldosterone ( P=0.012), renin ( P<0.01), and ARR ( P<0.01).Surgical outcomes were assessed using the Consensus on the Outcome of Surgery for Primary Aldosteronism (PASO) (complete/partial/no success for clinical and biochemical outcomes). CYP11B2 expression was evaluated by immunohistochemistry using the 2022 World Health Organization's histopathology of primary aldosteronism (HISTALDO) criteria. The correlation between the expression of CYP11B2 and surgical outcomes was assessed. Results:The mean follow-up of 99 patients was (11.73±4.92) months. Of these, 36 out of 59 PA patients had positive CYP11B2 expression in their adrenal specimens, while 23 were negative; all 40 NFA patients were negative for CYP11B2. Among the 36 CYP11B2-positive PA patients, there were 19 cases of aldosterone-producing adenomas, 3 aldosterone-producing nodules, 4 aldosterone-producing micronodules, 8 multiple aldosterone-producing micronodules, and 2 aldosterone-producing diffuse hyperplasia. 36 cases of CYP11B2-positive PA patients had complete clinical success in 15 cases, partial success in 20 cases, and no success in 1 case, and complete biochemical success in 24 cases, partial success in 11 cases, and no success in 1 case; 23 CYP11B2-negative PA patients had complete clinical success in 4 cases, partial success in 15 cases, and no success in 4 cases, and complete biochemical success in 6 cases, partial success in 15 cases, and no success in 2 cases. Adrenal specimens from CYP11B2-positive PA patients had significantly better clinical ( P=0.038) and biochemical ( P=0.008) success rates than CYP11B2-negative PA patients. Patients with aldosterone-producing adenomas had complete clinical success in 8 cases, partial success in 11 cases, and no success in 0 cases, and biochemical success was completely achieved in 16 cases, partially achieved in 2 cases, and not successful in 1 case. They also had significantly higher clinical ( P=0.028) and biochemical ( P<0.01) success rates compared to CYP11B2-negative PA patients. Conclusions:Patients with PA who had immunohistochemical staining for CYP11B2 positivity and high expression in adrenal specimens had a better postoperative clinical and biochemical prognosis. Patients with aldosterone-producing adenomas had the greatest postoperative outcome of all pathological subtypes of PA.

OBJECTIVE: To evaluate the predictive value of plasma heparin-binding protein (HBP) combined with albumin (Alb) for predicting 28-day mortality in patients with sepsis. METHODS: The clinical data of patients with sepsis admitted to the emergency intensive care unit (EICU) of the People's Hospital of Shenzhen Baoan District from March 2020 to March 2024 were retrospectively analyzed. The study began at the time of the first diagnosis of sepsis upon EICU admission and ended upon patient death or at 28 days. The gender, age, length of stay in EICU, underlying diseases, and infection sites were recorded. Within 24 hours of sepsis diagnosis, blood culture results, white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), blood lactate acid (Lac), HBP, Alb, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), mortality in emergency department sepsis score (MEDS), modified early warning score (MEWS), number of organ failures, use of vasopressors, application of mechanical ventilation, renal replacement therapy, and 28-day prognosis were recorded, the differences in these indicators between two groups were compared. Univariate and multivariate Logistic regression analyses were used to analyze the risk factors of 28-day mortality in patients with sepsis. Receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to evaluate the early predictive value of various risk factors for 28-day mortality in patients with sepsis. RESULTS: A total of 300 patients with sepsis were included, with 16 excluded, resulting in 284 patients being analyzed. Among them, 191 survived and 93 died within 28 days. There were no statistically significant differences between the two groups in terms of gender, age, underlying diseases, infection sites, blood culture positivity rate, number of organ failures, and length of stay in EICU. Univariate analysis showed that the rate of vasopressor use, the rate of mechanical ventilation, HBP, PCT, CRP, Lac, SOFA score, APACHE II score, MEDS score, and MEWS score were significantly higher in the death group than those in the survival group, while Alb was significantly lower in the death group than that in the survival group. Multivariate Logistic regression analysis showed that HBP and Alb were independent risk factors for predicting 28-day mortality in patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.093 (0.989-1.128) and 1.174 (1.095-1.259), both P < 0.05]. ROC curve analysis showed that both HBP and Alb had certain predictive value for 28-day mortality in patients with sepsis [AUC and 95%CI were 0.820 (0.717-0.923) and 0.786 (0.682-0.890), both P < 0.05]. When the critical value of HBP was 117.50 μg/L, the sensitivity was 85.90%, and the specificity was 70.50%. When the critical value of Alb was 28.30 g/L, the sensitivity was 69.30%, and the specificity was 81.20%. When the two indexes were combined for diagnosis, the AUC was 0.881 (95%CI was 0.817-0.945, P < 0.001), the sensitivity was 92.70%, and the specificity was 76.80%. CONCLUSIONS HBP and Alb are independent risk factors for predicting 28-day mortality in patients with sepsis. The combined prediction efficiency of HBP and Alb for 28-day mortality in patients with sepsis is superior to a single indicator.
Humans ; Sepsis/diagnosis* ; Retrospective Studies ; Predictive Value of Tests ; Intensive Care Units ; Blood Proteins/analysis* ; Prognosis ; Antimicrobial Cationic Peptides/blood* ; APACHE ; Male ; Female ; Organ Dysfunction Scores ; ROC Curve ; Middle Aged ; C-Reactive Protein/analysis* ; Emergency Service, Hospital ; Aged ; Hospital Mortality ; Serum Albumin/analysis*

Objective: To determine the association between anthropometric parameters and 20 meter shuttle run test (20 m SRT) score among children and adolescents. Methods: The convenient sampling method was conducted to select 3 192 primary and secondary school students in Baoan District, Shenzhen, based on the street school types school from April to May 2019. Height, weight, 20 m SRT score and general demographic indicators were assessed and collected. Individuals were divided into two groups based on the dose response correlation between different anthropometric parameters (the Z score of height, weight and BMI) and 20 m SRT score analyzed with the restricted cubic spline. The association between the Z score of height and 20 m SRT score was further analyzed using the Spearman correlation analysis. Logistic regression analysis was used to analyze separately the relationship different anthropometric parameters and 20 m SRT score. Results: The Z value of weight and 20 m SRT score showed a non linear dose response association ( P <0.01), the significant but weak linear correlation between the Z value of height and 20 m SRT score ( r=0.06, P <0.05). The prevalence rate on the low level of the Z value of 20 m SRT score in 3 192 children and adolescents was 44.7%, and the gender ( χ 2=14.02, P <0.01) and grade difference ( χ 2=93.28, P <0.01) were both statistically significant. There was no significant relationship between the Z value of height and 20 m SRT score grade among total population, different genders and different grades ( P > 0.05). Compared with the reference group on the Z value of weight ≤-0.23, individuals with the Z value of weight >-0.23 had the low level of 20 m SRT score ( OR =0.61, P <0.05). Compared with the reference group on the Z value of BMI ≤ 0.25, individuals with the Z value of weight >0.25 had the low level of 20 m SRT score ( OR =0.45, P <0.05). Stratified for gender and grade, the above significant relationship on the Z value of weight, Z value of BMI and 20 m SRT score were still observed ( P <0.01). Conclusions The higher height Z value shows on correlations with 20 m SRT score, but the positive association is found between weight and BMI Z value and the 20 m SRT score. The cardiopulmonary fitness improvement may be more effective among children and adolescents when tuking weight and BMI Z scores into consideration.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To investigate the effect and mechanism of artesunate (ARTS) combined with cytarabine(Ara-C) and/or daunorubicin (DNR) on the proliferation and apoptosis of MV4-11 human mixed-lineage leukemia rearranged（MLL-r） acute myeloid leukemia (AML) cell line. METHODS: CCK-8 assay was used to detect the proliferation effect of individual or in combination of ARTS, DNR, Ara-C on MV4-11 cells. The IC₅₀ of ARTS, DNR and Ara-C was calculated separately. The cell apoptosis and expression of receptors DR4 and DR5 were detected by flow cytometry. Western blot was used to detect the expression of Caspase-3 and Caspase-9 in each groups. RESULTS: The inhibition effect of ARTS, Ara-C and DNR on the proliferation of MV4-11 were all dose-dependently (r=0.99, 0.90 and 0.97, respectively). The IC₅₀ of ARTS, Ara-C and DNR on MV4-11 for 48 hours were 0.31 μg/ml, 1.43 μmol/L and 22.47 nmol/L, respectively. At the dose of ARTS 0.3 μg/ml， Ara-C 1.0 μmol/L and DNR 15 nmol/L, the proliferation rate for 48 hours of the tri-combination treatment was significantly lower than that of the bi-combination treatment, while both were significantly lower than that of the individual treatment (all P＜0.05). In terms of bi-combination treatment, the cells proliferation rate for 48 hours of the ARTS+Ara-C group was significantly lower than that of the ARTS+DNR group, while both were significantly lower than that of the Ara-C+DNR group (all P＜0.05). The cooperativity index (CI) of bi- and tri-combination treatment were all less than 1. After 48 hours of drug action, the cell apoptosis rate of the ARTS+DNR+Ara-C group was significantly higher than that of the Ara-C+DNR group, while both were significantly higher than that of the ARTS+DNR group (all P＜0.05). Meanwhile, the was no statistical difference between the cells apoptotic rate of the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (P>0.05). The expression of DR4 and DR5 also showed no difference between control group and drug group. Compared with the DNR+Ara-C group, the expressions of Caspase-3 were significantly down-regulated in both the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (all P＜0.05). The down-regulation of Caspase-3 expression was the most significantly in the combination group of three drugs, while the Caspase-9 expressions in different groups showed no apparent change. CONCLUSION The in vitro study showed that tri-combination of ARTS+Ara-C+DNR and bi-combination of ARTS+Ara-C could inhibit the proliferation and promote apoptosis of MV4-11 cell line. The inhibition effect of these two combinations were significantly superior to that of the traditional Ara-C+DNR treatment. The mechanism underlying this finding may be identified by the down regulation of Caspase-3, while no altered expression was observed of Caspase-9, DR4 and DR5.
Humans ; Cytarabine/pharmacology* ; Daunorubicin/pharmacology* ; Caspase 3 ; Caspase 9 ; Artesunate/pharmacology* ; Leukemia, Myeloid, Acute ; Apoptosis ; Cell Line

Objective: To explore the value of an oral squamous cell carcinoma (OSCC) diagnostic model constructed by using principal component analysis (PCA) to analyze a database of differentially expressed genes in OSCC and to provide a reference for clinical diagnosis and treatment. Methods: RNA-seq expression data of OSCC and normal control samples were obtained from The Cancer Genome Atlas (TCGA) database, and then, normalized and differentially expressed genes (DEGs) were identified by R software. DEGs were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify their main biological characteristics. 70% of DEGs expression data in RNA-seq were randomly selected as the training set and 30% were selected as the test set. Then, the PCA method was applied to analyze the training set data and extract the principal components (PCs) related to the diagnosis of OSCC in order to construct a PCA model. Then, the receiver operating characteristic (ROC) curves of PCA models in the training set and the test set were respectively drawn, and the area under curve (AUC) was calculated to evaluate the accuracy of the PCA model in the diagnosis of OSCC. Results: RNA-seq expression data of OSCC and normal control samples obtained from TCGA database included 330 samples and 32 samples, respectively. Using false discovery rate (FDR) <0.001 and |log2 fold change| (|log2FC|) >4 as the thresholds, a total of 159 downregulated and 248 upregulated DEGs were identified, which were mainly enriched in cellular components such as intermediate fiber and melanosomal membrane, pigment and salivation-related biological processes and mainly involved in salivary secretion and tyrosine metabolism pathways (P.adjust<0.05 and Q<0.05). The DEGs were proposed as tumor markers for OSCC, and PCA analysis of the training set showed that the cumulative ratio of variance of PC1, PC2 and PC3: [including submaxillary gland androgen regulated protein 3B (SMR3B), proline rich 27 (PRR27), histatin 3 (HTN3), statherin (STATH), cystatin D (CST5), BPI fold containing family A member 2 (BPIFA2), proline rich protein Hae Ⅲ subfamily 2 (PRH2), keratin 35(KRT35), histatin 1 (HTN1), amylase alpha 1B (AMY1B)] were 0.873, 0.100 and 0.023, respectively, and the total weight of the three was 0.996. The PCA diagnostic model of OSCC was further constructed by combining the eigenvectors of the above three components. The ROC curves of the training set and test set showed that the AUC values of the PCA model were 0.852 and 0.844, respectively, which were higher than those of other single genes. Conclusion The OSCC diagnostic model based on the expression levels of SMR3B, PRR27, HTN3, STATH, CST5, BPIFA2, PRH2, KRT35, HTN1 and AMY1B constructed with the PCA method and DEGs has a high diagnostic advantage. This study provides a theoretical basis for the early genetic diagnosis of OSCC and the application of the PCA model in clinical diagnosis.