Objective To construct a risk prediction model of post-traumatic stress disorder(PTSD)after hypertensive intracerebral hemorrhage in elderly patients and analyze the correla-tion of PTSD with rs806377 polymorphism of cannabinoid receptor 1(CNR1)gene.Methods A total of 215 elderly patients with hypertensive cerebral hemorrhage admitted to the Department of Neurology of Geriatric Hospital of Hainan and Department of Neurosurgery of the First Affiliated Hospital of Hainan Medical University from January 2020 to August 2022 were enrolled in this study.According to the results of PTSD scale(scoring＞50 or 0～50)after surgical treatment,they were divided into PTSD group(43 cases)and non-PTSD group(172 cases).The rs806377 polymorphism of CNR1 gene was detected in both groups by gene sequencing.Univariate and mul-tivariate logistic regression analyses were used to analyze the susceptibility to PTSD among the elderly after hypertensive intracerebral hemorrhage.Another 103 elderly patients with hyperten-sive intracerebral hemorrhage during the same period were also subjected and served as verifica-tion set.A prediction model was constructed.Results There were significant differences in age,family annual income,blood loss amount,psychological resilience score and social support score between the PTSD group and non-PTSD group(P＜0.05,P＜0.01).The PTSD group had obvi-ously larger proportion of TT genotype carriers and higher T allele frequency than the non-PTSD group(P＜0.05,P＜0.01).Logistic regression analysis showed that age(OR=2.020,95％CI:1.115-3.658),family annual income(OR=1.799,95％CI:1.232-2.626),blood loss(OR=1.507,95％CI:1.243-1.826),psychological resilience score(OR=2.059,95％CI:1.068-3.969),social support score(OR=1.664,95％CI:1.122-2.467),rs806377 TT genotype(OR=1.861,95％CI:1.485-2.331)and rs806377 T allele(OR=3.777,95％CI:2.049-6.962)were the influencing fac-tors of postoperative PTSD in these patients(P＜0.05,P＜0.01).ROC curve analysis indicated that the sensitivity was 69.57％,the specificity was 71.25％,and the AUC value was 0.762(95％CI:0.708-0.813)in the verification group,indicating a certain accuracy of our model.Conclusion CNR1 gene rs806377 locus polymorphism is an influencing factor for PTSD susceptibility,and rs806377 TT genotype and rs806377 T allele can predict PTSD in elderly patients after hyperten-sive intracerebral hemorrhage.

Objective:To explore the status of "socialized hospitalization" of chronic obstructive pulmonary disease (COPD) patients and its influencing factors, and propose constructive coping strategies.Methods:From June 2018 to June 2020, convenience sampling was used to select 256 COPD patients admitted to Hangzhou First People's Hospital as the research object. The self-designed Socialized Hospitalization Status and Influencing Factors Questionnaire was used to investigate patients. Single factor analysis and multivariate Logistic regression analysis were used to analyze the influencing factors of the "socialized hospitalization" of COPD patients.Results:Among 256 COPD patients, 239 effective samples were finally obtained, and 61 cases (25.52%) were "socialized hospitalization". The hospitalization time of patients with "socialized hospitalization" was longer than those with non-"socialized hospitalization", and the difference was statistically significant ( t=16.510, P<0.01) . Hospitalization expenses were higher than those with non-"socialized hospitalization", and the difference was statistically significant ( t=17.820, P<0.01) . The results of single factor analysis showed that there were statistically significant differences in the age, course of illness, type of medical insurance, hospital admission method, hospital-acquired infection, mental status score, dyspnea score, and basic life activity ability in patients with "socialized hospitalization" and non-"socialized hospitalization" ( P<0.05) . The results of multivariate Logistic regression analysis showed that the patient's age, type of medical insurance, hospital admission method, hospital-acquired infection, mental status, dyspnea, and basic life activity ability were the influencing factors of COPD patients' "socialized hospitalization", and the difference was statistically significant ( P<0.05) . Conclusions:Various physiological and pathological conditions and family conditions are the influencing factors of "socialized hospitalization" in COPD patients. The allocation of medical resources should be balanced, the nursing system should be perfected, and the technical level and quality of medical and nursing staff should be improved to ease the pressure of "socialized hospitalization".

Objective To investigate the fatigue in patients with type 2 diabetes mellitus (T2DM),and analyze its related factors.Methods A total of 211 patients with type 2 diabetes were investigated with Chinese version of Multidimensional Fatigue Inventory-20 (MFI-20),Medical Outcomes Study Health Status Short Form-Vitality (SF-36-VT) and demographic survey questionnaire.T test,one-way AVOVA and multiple linear regression analysis were used to analyze the data.Results The fatigue incidence of 211cases of patients with type 2 diabetes was 63.5％ (134/211),the mean score of MFI-20 was 54.10±15.63,and women's score (57.89±15.32) was significantly higher than that of men (51.54±15.37)(t=2.949,P ＜ 0.01).Physical fatigue got the highest score of the three dimensions in MFI-20,which was 2.99±1.03,the mental fatigue scored 2.67±0.82.Multiple linear regression analysis showed that fatigue was related to the sports,2hPBG,rest situation,cerebrovascular complications and the number of complications,which could totally explain 30.7％ of the variance.Conclusions More attention should be paid to fatigue of T2DM patients.Effective interventions should be carried out to relieve the fatigue status of T2DM patients and improve their self-management ability and quality of life.

OBJECTIVE:To observe clinical efficacy of urinary kallidinogenase in the treatment of acute cerebral watershed in-farct (WSI). METHODS:128 patients with WSI were randomly divided into control group and treatment group,each of the 64 cases. Control group was given Shuxuening 15 ml added into 0.9% Sodium chloride 250 ml,ivgtt,qd;treatment group received urinary kallidinogenase 0.15 PNA added into 0.9% Sodium chloride 100 ml,ivgtt,qd. Both groups were treated for consecutive 14 days. Neurologic impairment score(NIHSS)and clinical efficacy were observed in 2 groups before treatment and 3,7 and 14 days after treatment. The blood specimens were collected after 7 and 14 days treatment,to determine serum levels of TCC. RESULTS:After treatment,NIHSS and total effective rate of treatment group were significantly higher than those of control group,with statis-tical significance(P<0.01). There was no statistical significance in TCC between 2 groups before treatment(P>0.05);7 days af-ter treatment,TCC level of 2 groups increased significantly,to 14 days,and a declive;the treatment group was higher than the control group,with statistical significance (P<0.05). CONCLUSIONS:Urinary kallidinogenase can improve clinical efficacy of WSI significantly,and promote neurologic impairment symptom and TCC levels.

OBJECTIVETo investigate the effect of CAL-101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL-2 and Jeko-1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma.

METHODSMTT assay was applied to detect the inhibitory effects of CAL-101 and bortezomib either alone or combined on Z138, HBL-2 and Jeko-1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K-p110σ and p-Akt, Akt, p-ERK and ERK proteins after the cells were exposed to different concentrations of CAL-101. Flow cytometry was employed to assess the apoptosis rate. NF-κB kit was used to determine the changes of location of NF-κB P65, and Western blot was applied to detect the level of caswpase-3 and the phosphorylation of Akt in different groups.

RESULTSCAL-101 and BTZ inhibited the proliferation of Z138, HBL-2 and Jeko-1 cells in a dose- and time-dependent manner. CAL-101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL-101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL-101 combined with BTZ induced pronounced apoptosis (P < 0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL-101, BTZ and CAL-101 + BTZ groups were: (2.6 ± 1.8)%, (40.0 ± 3.0)%, (34.0 ± 1.0)%, and (67.4 ± 1.0)%, respectively; and when drug treatment was given to HBL-2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4 ± 0.6)%, (30.7 ± 5.7)%, (12.0 ± 1.0)%, and (85.0 ± 4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor-κB (NF-κB) and Akt inactivation in the MCL cell lines (P < 0.05), however, the casepase-3 activity was up-regulated.

CONCLUSIONSThe combination of CAL-101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines (Z138, HBL-2 and Jeko-1), which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF-κB.

Antineoplastic Agents ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Boronic Acids ; Bortezomib ; pharmacology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Class Ia Phosphatidylinositol 3-Kinase ; antagonists & inhibitors ; Dose-Response Relationship, Drug ; Drug Synergism ; Formazans ; Humans ; Lymphoma, Mantle-Cell ; drug therapy ; pathology ; MAP Kinase Signaling System ; drug effects ; NF-kappa B ; metabolism ; Neoplasm Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Purines ; administration & dosage ; pharmacology ; Pyrazines ; Quinazolinones ; administration & dosage ; pharmacology ; Signal Transduction ; Software ; Tetrazolium Salts

OBJECTIVETo elucidate the impact of Hes1 on the proliferation and apoptosis of acute myeloid leukemia (AML) cells.

METHODSThe expression levels of Hes1 and p21 in AML patient samples and myeloid leukemia cell lines were analyzed by real-time PCR. Hes1 was up-regulated by retrovirus transfection in AML cell lines and the proliferation capacity were assayed by MTT, cell cycle by Hoechst/PY, apoptosis by AnnexinV.

RESULTSThe expression of Hes1 in primary AML cells and HL-60, U937, KG1a cell lines were 0.67 ± 0.24, 0.59 ± 0.43, 0.42 ± 0.03, and 0.32 ± 0.26, respectively, and p21 were 0.54 ± 0.01, 0.44 ± 0.12, 0.36 ± 0.12, and 0.59 ± 0.43, respectively. Hes1 expression levels after transduction in HL-60, U937, KG1a were 4.9 ± 0.2, 5.2 ± 0.4, 5.8 ± 0.5, respectively. Induced activation of Hes1 led to AML cells growth arrest and apoptosis, which was associated with an enhanced p21 expression. Besides, activated Hes1 led to AML cells growth inhibition in vivo.

CONCLUSIONHes1 could mediate growth arrest and apoptosis in AML cells, which may be a novel target for AML.

Apoptosis ; Basic Helix-Loop-Helix Transcription Factors ; Cell Cycle ; Cell Line, Tumor ; Homeodomain Proteins ; Humans ; Leukemia, Myeloid, Acute ; Transcription Factor HES-1 ; Up-Regulation

Objective:To detect the inhibitory effects of CAL-101, a selective inhibitor of phosphoinostitide-3'-kinase delta (PI3Kδ), on Burkitt's lymphoma cell line Raji and diffused large B-cell lymphoma cell line SUDHL-10 and elucidate its relative mechanism. Methods:Raji and SUDHL-10 cells were treated with various concentrations of CAL-101. Methyl thiazolyl tetrazolium (MTT) assay was performed to determine the inhibitory effect of CAL-101 on lymphoma cells, and cell apoptosis was measured by Annexin V/PI and DAPI staining. Migration assays were performed with transwell to detect the migration of lymphoma cells derived from the stromal cell line HK. Western blot was used to detect the phosphorylation status of the ERK pathway. MTT and CalcuSyn software analyses were preformed to detect whether or not combining CAL-101 with bortezomib induces synergistic cytoxicity. Results:CAL-101 at con-centrations of 5, 10, 15, and 20μmol/L inhibited cell proliferation in a dose-dependent manner. The proliferation rates of the Raji cells treated with 5, 10, 15, and 20μmol/L for 48 h were 29.17%± 1.23%, 38.15%± 1.51%, 46.46%± 1.78%, and 55.8%± 2.01%, respec-tively, which were significantly higher (P<0.05) than that of the control group (1.15% ± 0.02%). Similar results were found in the SUDHL-10 cells after treatment with CAL-101 (P<0.05). CAL-101 also exerted an apoptotic effect on the lymphoma cells. The apop-totic rates of the Raji cells treated with CAL-101 for 21 h were 22.69%± 3.83%and 49.96%± 7.36%, respectively, which were signifi-cantly higher (P<0.05) than that of the control group (5.23%± 2.04%). Similar results were found in the SUDHL-10 cells (P<0.05). Treatment with 5 and 10 μmol/L CAL-101 dose-dependently inhibited the migration activity of lymphoma cells to stromal cells (P<0.05). Western blot analysis showed that the expression level of ERK phosphorylation protein was significantly downregulated in the cells treated with CAL-101. A synergistic effect between CAL-101 and bortezomib was verified. That is, these two drugs can signifi-cantly inhibit the proliferation of lymphoma cells with CI values less than 1. Conclusion:The PI3Kδ-specific inhibitor CAL-101 sup-pressed the proliferation of Raji and SUDHL-10 cells, induced apoptosis, and inhibited stromal cell-derived migration. This inhibitory effect may be induced by blocking the ERK pathway. Overall, our study indicated that CAL-101 is a novel and potential agent in the therapeutic strategy against aggressive B-cell lymphoma.

Objective To investigate the effect of CAL?101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL?2 and Jeko?1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma. Methods MTT assay was applied to detect the inhibitory effects of CAL?101 and bortezomib either alone or combined on Z138, HBL?2 and Jeko?1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K?p110σ and p?Akt, Akt, p?ERK and ERK proteins after the cells were exposed to different concentrations of CAL?101. Flow cytometry was employed to assess the apoptosis rate. NF?κB kit was used to determine the changes of location of NF?κB P65, and Western blot was applied to detect the level of caswpase?3 and the phosphorylation of Akt in different groups. Results CAL?101 and BTZ inhibited the proliferation of Z138, HBL?2 and Jeko?1 cells in a dose? and time?dependent manner. CAL?101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL?101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL?101 combined with BTZ induced pronounced apoptosis (P<0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL?101, BTZ and CAL?101+BTZ groups were:(2.6±1.8)%, (40.0±3.0)%, (34.0±1.0)%, and (67.4±1.0)%, respectively; and when drug treatment was given to HBL?2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4±0.6)%,(30.7±5.7)%, (12.0±1.0)%, and (85.0±4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor?κB ( NF?κB) and Akt inactivation in the MCL cell lines (P<0.05), however, the casepase?3 activity was up?regulated. Conclusions The combination of CAL?101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines ( Z138, HBL?2 and Jeko?1) , which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF?κB.

Objective To investigate the effect of CAL?101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL?2 and Jeko?1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma. Methods MTT assay was applied to detect the inhibitory effects of CAL?101 and bortezomib either alone or combined on Z138, HBL?2 and Jeko?1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K?p110σ and p?Akt, Akt, p?ERK and ERK proteins after the cells were exposed to different concentrations of CAL?101. Flow cytometry was employed to assess the apoptosis rate. NF?κB kit was used to determine the changes of location of NF?κB P65, and Western blot was applied to detect the level of caswpase?3 and the phosphorylation of Akt in different groups. Results CAL?101 and BTZ inhibited the proliferation of Z138, HBL?2 and Jeko?1 cells in a dose? and time?dependent manner. CAL?101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL?101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL?101 combined with BTZ induced pronounced apoptosis (P<0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL?101, BTZ and CAL?101+BTZ groups were:(2.6±1.8)%, (40.0±3.0)%, (34.0±1.0)%, and (67.4±1.0)%, respectively; and when drug treatment was given to HBL?2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4±0.6)%,(30.7±5.7)%, (12.0±1.0)%, and (85.0±4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor?κB ( NF?κB) and Akt inactivation in the MCL cell lines (P<0.05), however, the casepase?3 activity was up?regulated. Conclusions The combination of CAL?101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines ( Z138, HBL?2 and Jeko?1) , which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF?κB.

OBJECTIVETo investigate the proliferation inhibitory role and mechanism of PI3Kδ inhibitor CAL-101 on multiple myeloma (MM) cells, and to provide new therapeutic options for MM treatment.

METHODSMM cell lines U266 and RPMI8226 cells were treated with various concentrations of CAL-101. MTT assay and CalcuSyn software were performed to determine the inhibitory effect of CAL-101 and the synergistic effect with PCI- 32765, SAHA (suberoylanilide hydroxamic acid), BTZ (Bortezomib) on MM cells. The protein expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ processed by CAL-101 were analyzed by Western blot.

RESULTSCAL-101 at concentration of 15, 20, 25, 30 and 40 μmol/L could induce significant dose-dependent proliferation inhibition on U266 cells after treatment for 48 hours. The cell proliferation inhibition rates were (33.54 ± 1.23)%, (41.72 ± 1.78)%, (53.67 ± 2.01)%, (68.97 ± 2.11)% and (79.25 ± 1.92)%, respectively. Similar results were found in RPMI8226 cell line. Western blots showed high expression level of p-AKT, p-ERK, AKT, ERK and PI3Kδ in cell lines and MM primary cells. p-AKT and p-ERK protein expression levels were down-regulated significantly by CAL-101 treatment. Synergistic effect has been verified between CAL-101 and PCI-32765, SAHA and Bortezomib in U266 cell line, and PCI-32765, Bortezomib in RPMI8226 cell line with CI values less than 1.

CONCLUSIONCAL-101 could inhibit proliferation of MM cell lines. High levels of p-AKT, p-ERK, AKT, ERK and PI3Kδ protein expression were observed in both cell lines and primary cells. Down-regulation of p-AKT and p-ERK probably related with the mechanism of CAL-101 in MM cell proliferation inhibition. CAL-101 has significant synergistic effect with PCI-32765, SAHA and BTZ.

Boronic Acids ; Bortezomib ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Humans ; Multiple Myeloma ; pathology ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; Protein Kinase Inhibitors ; pharmacology ; Purines ; pharmacology ; Pyrazines ; Pyrazoles ; Pyrimidines ; Quinazolinones ; pharmacology