A large number of natural acetogenins have been isolated from se veral genera of the plant family Annonaceae. Many of these compounds have very p otent and diverse biological effects such as cytotoxic, antitumour, anti-malari al, pesticidal and anti-feedant activities. This paper reviews research finding s about the effects of annonaceous acetogenins on antitumor, MDR, mechanism of ac tion, structural-activity relationships etc.

AIM: To determine whether Jiunaoning injection has protective effects on oxygen/glucose-deprived and reperfusion injury-induced neurons. METHODS: Various concentrations of Jiunaoning injection (0.5-5 mL/L) were used to observe their effects on cultured rat cortical neurons induced by oxygen/glucose-deprived and reperfusion injury in various time points. The neuronal metabolic rate and viability were assessed by using 3-(4,5-dimethylthiazol)-2, 5-diphenyl-tetra zoliumbromide (MTT) and lactate dehydrogenase (LDH) assay. RESULTS: Jiunaoning injection enhanced the neuronal metabolic rate in a dose-dependent manner in the range from 0.5 to 5 mL/L, and Jiunaoning injection (1.5-2.5 mL/L) enhanced the neuronal metabolic rate, decreased the cell death rate and depressed LDH leak rate significantly. CONCLUSION: Jiunaoning injection has an affirmative protective effect on oxygen/glucose-deprived and reperfusion-induced neuronal injury.

OBJECTIVE To investigate the distribution and characterization of the classes Ⅰ,Ⅱ and Ⅲ integrons on Stenotrophomonas maltophilia and clarify their influence on the bacterial drug-resistance.METHODS A multi-PCR assay using specific primers of int1,int2 and int3 was constructed to screen classes Ⅰ,Ⅱ and Ⅲ integrons.RESULTS Class Ⅰ integron was detected in 13.4% of clinical isolates,3 isolates harbored among class Ⅱ integrons. There was not been reported in abroad.CONCLUSIONS Classes Ⅰ and Ⅱ integrons could play an important role in causing the antibiotic multidrug resistance.

Objective To investigate the distribution and quantitative changes in each marshland of Changsha section of the Xiang River and evaluate the effectiveness of snail control in recent years.Methods A snail survey was carried out by using the systematic and environmental sampling method for 5 years.Results Twenty-four marshlands were investigated continuously from 2003 to 2007.The number of marshland with snails accounted for 77.8%,66.7%,70.8%,75.0% and 62.5% of the each investigated year,respectively.The total number of marshlands with snails were 20 that accounted for 83.3% of all marshlands investigated over the five years.The number of snails and the rate of living snails were different in each marshland,but the downward trend was significant(P

Objective:To explore the clinical curative effect of nifedipine controlled-release tablets combined with telmisartan on diabetes mellitus combined with hypertension and their influences on serum homocysteine (Hcy) and C-reactive protein (CRP).Methods:Eighty-four patients with diabetes mellitus and hypertension who were admitted to Huainan First People′s Hospital from February 2016 to November 2019 were enrolled. They were divided into combination group and control group by random number table method, with 42 cases in each group. The control group was treated with nifedipine controlled-release tablets, while combination group was additionally treated with telmisartan. Both groups were continuously treated for 4 weeks. After treatment, clinical curative effect in both groups was evaluated. The levels of diastolic blood pressure (DBP), systolic blood pressure (SBP), fasting plasma glucose (FPG), 2 h postprandial blood glucose (2 hPG), glycosylated hemoglobin (HbA 1c), total cholesterol (TC), triacylglycerol (TG), Hcy and CRP were measured before and after treatment. The number of cases with adverse reactions was recorded. Results:After treatment, total response rate in combination group was significantly higher than that in control group [92.24%(40/42) vs. 80.95%(34/42)] ( P<0.05). After treatment, there were no significant differences in FPG, 2 hPG and HbA 1c between the two groups ( P>0.05). After treatment, the levels of SBP, DBP, TC, TG, CRP and Hcy in combination group were significantly lower than those in control group [(132.64 ± 7.53) mmHg)(1 mmHg=0.133 kPa) vs. (142.81 ± 4.63) mmHg, (79.63 ± 6.84) mmHg vs.(85.71 ± 5.86) mmHg, (4.87 ± 0.61) mmol/L vs. (5.14 ± 0.62) mmol/L, (1.57 ± 0.41) mmol/L vs.(1.76 ± 0.45) mmol/L,(8.76 ± 1.53) mg/L vs. (9.51 ± 1.86) mg/L, (12.52 ± 1.97) μmol/L vs.(13.48 ± 2.36) μmol/L]( P<0.05). During treatment period, there was no significant difference in incidence of adverse reactions between combination group and control group [16.67% (7/42) vs. 19.05%(8/42)]( P>0.05). Conclusions:The clinical curative effect of nifedipine controlled-release tablets combined with telmisartan is good on diabetes mellitus combined with hypertension, which can regulate blood pressure, blood lipids, Hcy and CRP levels, and relieve disease progression, with good safety.

OBJECTIVETo study the expression and significance of tumor suppressor in lung cancer 1 (TSLC1) gene methylation, the expression of TSLC1 protein in cervix cancer and precancerous lesions as well as their relationship with HR-HPV DNA infection.

METHODSThe clinicopathological data of 92 cases of different cervical lesions during March 2011 to August 2012 treated in our hospital were collected. There were pathologically confirmed 10 cases of normal cervix, 26 cases of cervical intraepithelial neoplasia (CIN) I, 20 cases of CIN II, 15 cases of CIN III, and 21 cases of cervical cancer. Methylation-specific polymerase chain reaction (MSP) was used to detect the TSLC1 gene methylation status in cervical lesions, immunohistochemistry (SP) was used to detect the expressions of TSLC1 protein in cervical lesions, and the second generation hybrid capture (HC2) method was used to detect the high-risk HPV in cervical lesions.

RESULTSThe expression rate of TSLC1 gene methylation in normal cervical tissue, CIN I, CIN II, CIN III and SCC were 10.0%, 30.8%, 55.0%, 60.0%, 66.7%, respectively, showing a statistically significant difference (P = 0.004). The positive expression rate of TSLC1 protein in normal cervical tissue, CIN I, CIN II, CIN III and SCC were 100.0%, 80.8%, 65.0%, 33.3%, and 23.8%, respectively, with a significant difference (P = 0.004). In the progression from CIN to invasive cervical cancer, there was no significant correlation between TSLC1 gene methylation and HR-HPV DNA infection (P = 0.919), TSLC1 protein expression and HR-HPV DNA infection (P = 0.664). The correlation analysis showed a negative correlation between TSLC1 gene methylation and TSLC1 protein expression (r = -0.674, P < 0.001).

CONCLUSIONSTSLC1 gene promoter methylation may be an early event in the cervical carcinogenesis, become an early sensitive marker, and serve the early prevention and prognostic prediction for cervical cancer.

Cell Adhesion Molecule-1 ; Cell Adhesion Molecules ; genetics ; metabolism ; Cervical Intraepithelial Neoplasia ; genetics ; metabolism ; DNA Methylation ; Disease Progression ; Female ; Humans ; Immunoglobulins ; genetics ; metabolism ; Immunohistochemistry ; Methylation ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Uterine Cervical Neoplasms ; genetics ; metabolism

Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo. Mechanistically, alectinib increased the intracellular accumulation of ABCB1/ABCG2 substrates such as doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, alectinib stimulated ATPase activity and competed with substrates of ABCB1 or ABCG2 and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling bound to ABCB1 or ABCG2 but neither altered the expression and localization of ABCB1 or ABCG2 nor the phosphorylation levels of AKT and ERK. Alectinib also enhanced the cytotoxicity of DOX and the intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. These findings suggest that alectinib combined with traditional chemotherapy may be beneficial to patients with ABCB1- or ABCG2-mediated MDR.
Adenosine Triphosphatases ; Carcinoma, Non-Small-Cell Lung ; Doxorubicin ; Drug Resistance, Multiple* ; Drug Therapy ; Humans ; In Vitro Techniques* ; Leukemia ; Lymphoma ; Parents ; Phosphorylation ; Phosphotransferases ; Rhodamine 123 ; United States Food and Drug Administration

Objective To explore the effect of chloroquine on death receptor 5 (DR5) expression of hepatocellular carcinoma Huh7 cells and cell proliferation and apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL).Methods Huh7 cells were divided into four groups:the control group (1∶1 000 dimethyl sulfoxide),TRAIL group (50 μg/L),chloroquine group (10 μmol/L) and TRAIL +chloroquine group (TRAIL 50 μg/L + chloroquine 10 μmol/L).Thiazolyl blue tetrazolium bromide (MTT) assay was used to determine the proliferation activity of cells,immunofluorescence was used to detect the expression of DR5,4',6-diamidino-2-phenylindole (DAPI) staining was used to observe cell apoptosis and Western blot was used to detect the expression of cleaved poly ADP-ribose polymerase (PARP).Results TRAIL treatment could decrease Huh7 cells proliferation activity;when compared with the cell viability in the control group,the cell proliferation inhibition rate of chloroquine group,TRAIL group and TRAIL+ chloroquine group was (89±8) ％,(53±10) ％ and (27±7) ％,respectively;compared with TRAIL group alone,cell proliferation activity was decreased in TRAIL+ chloroquine group (t =3.922,P =0.017).The expression of DR5 was upregulated in chloroquine group,and the cell apoptosis signaling was activated in TRAIL + chloroquine group.The cell apoptosis rate of TRAIL group and TRAIL + chloroquine group was (10.0±2.3) ％ and (20.4±4.0) ％,respectively,and there was a statistical difference (t =3.894,P =0.018).Conclusion Chloroquine can enhance the cell chemosensitivity to TRAIL treatment by upregulating the expression of DR5 in Huh7 cells.

Objective:To investigate the clinical characteristics and prognosis of duodenal neuroendocrine neoplasms.Methods:The clinical data of 35 patients with duodenal neuroendocrine neoplasms admitted to Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from Jan 2012 to Dec 2021 were retrospectively analyzed. The differences of clinical characteristics between periampullary and non-periampullary duodenal neuroendocrine neoplasms were analyzed. Kaplan-Meier curve was used for survival analysis, and the clinical factors affecting the prognosis were analyzed.Results:Of the 35 patients, 30 underwent tumor resection, 7 (23%) developed different degree of complications after operation and were improved and discharged after intervention. A total of 5 patients died during the follow-up period. Only 1 of 30 patients who underwent tumor resection died 30 months after operation due to disease progression, and the others had no recurrence or metastasis. Univariate analysis showed that tumor size, tumor grade, and tumor location were associated with the prognosis of patients (all P<0.05), and multivariate analysis showed that patients with tumors located.Away from the ampulla had a significantly better prognosis than those located around the duodenal ampulla ( P<0.01). Conclusions:Patients with duodenal neuroendocrine neoplasms have a good prognosis after complete resection; patients with duodenal neuroendocrine neoplasms located around the ampulla of Vater have a relatively poor prognosis compared with those away from the area of ampulla.