A series of cycloberberine derivatives were designed, synthesized and evaluated for their anti-cancer activities in vitro. Among these analogs, compounds 6c, 6e and 6g showed strong inhibition on human HepG2 cells. They afforded a potent effect against DOX-resistant MCF-7 breast cells as well. The primary mechanism showed that cell cycle was blocked at G2/M phase of HepG2 cells treated with 6g using flow cytometry assay. It significantly inhibited the activity of DNA Top I at the concentration of 0.1 mg mL-1. Our results provided a basis for the development of this kind of compounds as novel anti-cancer agents.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Berberine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; DNA Topoisomerases, Type I ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Molecular Structure ; Structure-Activity Relationship

A series of novel N-(2-arylethyl) isoquinoline derivatives were designed, synthesized and evaluated for their anti-cancer activities. Among these analogs, compound 9a exhibited the potential anti-cancer activities on HepG2 and HCT116 cells with IC50 values of 2.52 and 1.99 microg x mL(-1), respectively. Cell cycle was blocked at S phase of HepG2 cells treated with 9a by flow cytometry detection. Our results provided a basis for the development of a new series of anti-cancer candidates.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; HCT116 Cells ; Hep G2 Cells ; Humans ; Inhibitory Concentration 50 ; Isoquinolines ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Structure-Activity Relationship

OBJECTIVETo study the levels of blood lipid among Chinese adults in 2010 and analyze the epidemiological features.

METHODSFasting serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were determined for 90 395 subjects aged 18 and over who were selected by multi stage cluster random sampling method from 162 surveillance sites of 31 provinces of China mainland in 2010. After complex weighting, the differences of levels of serum total TC, TG, HDL-C and LDL-C were analyzed in different age, gender and geographic regions.

RESULTSAfter complex weighting, the levels of serum TC in Chinese adults was (4.04 ± 1.08) mmol/L, with (3.86 ± 1.03), (4.29 ± 1.11) and (4.33 ± 1.09) mmol/L in the groups of 18 - 44, 45 - 59 and over 60 years old (F = 177.56, P < 0.01), respectively. The level of serum TC was (4.06 ± 1.09) mmol/L and (4.03 ± 1.07) mmol/L in males and females (F = 2.38, P > 0.05), respectively; (4.08 ± 1.13) mmol/L and (4.03 ± 1.06) mmol/L in urban and rural areas (F = 0.51, P > 0.05), respectively, and (4.13 ± 1.11), (4.03 ± 1.01) and (3.93 ± 1.11) mmol/L in areas of east, middle and west respectively (F = 2.56, P > 0.05). The levels of serum TG was (1.33 ± 1.28) mmol/L, with(1.26 ± 1.24), (1.48 ± 1.46) and (1.35 ± 1.05) mmol/L in the groups of 18 - 44, 45 - 59 and over 60 years old (F = 85.98, P < 0.01), respectively. The level of serum TG was (1.45 ± 1.48) mmol/L and (1.21 ± 1.01) mmol/L in males and females (F = 172.01, P < 0.01), respectively, (1.34 ± 1.26) mmol/L and (1.33 ± 1.28) mmol/L in urban and rural areas (F = 0.16, P > 0.05), respectively, and(1.30 ± 1.25), (1.35 ± 1.23) and (1.35 ± 1.36) mmol/L in areas of east, middle and west (F = 0.69, P > 0.05) respectively. The levels of serum HDL-C was (1.11 ± 0.31) mmol/L, with (1.09 ± 0.30), (1.13 ± 0.33) and (1.14 ± 0.33) mmol/L in the groups of 18 - 44, 45 - 59 and over 60 years old (F = 27.81, P < 0.01), respectively. The level of serum HDL-C was (1.08 ± 0.32) mmol/L and (1.14 ± 0.30) mmol/L in males and females (F = 178.66, P < 0.01), respectively, (1.11 ± 0.31) mmol/L and (1.11 ± 0.32) mmol/L in urban and rural areas (F = 0.09, P > 0.05), respectively, and (1.12 ± 0.32), (1.12 ± 0.31) and (1.09 ± 0.32) mmol/L in areas of east, middle and west (F = 1.06, P > 0.05) respectively. The levels of serum LDL-C was (2.27 ± 0.78) mmol/L, with (2.15 ± 0.74), (2.42 ± 0.80) and (2.46 ± 0.81) mmol/L in the groups of 18 - 44, 45 - 59 and over 60 years old (F = 129.84, P < 0.01), respectively. The level of serum LDL-C was (2.30 ± 0.78) mmol/L and (2.24 ± 0.78) mmol/L in males and females (F = 25.06, P < 0.01), respectively, (2.33 ± 0.82) mmol/L and (2.24 ± 0.76) mmol/L in urban and rural areas (F = 3.48, P > 0.05), respectively, and (2.35 ± 0.80), (2.25 ± 0.74) and (2.17 ± 0.77) mmol/L in areas of east, middle and west (F = 4.58, P < 0.05) respectively.

CONCLUSIONThe levels of serum lipid of middle aged male, female after menopause and people living in eastern region were higher than other Chinese adults. Effective measures should be taken earlier to control serum lipid levels.

Adolescent ; Adult ; Age Distribution ; Asian Continental Ancestry Group ; China ; epidemiology ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Cross-Sectional Studies ; Dyslipidemias ; epidemiology ; Female ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Sex Distribution ; Triglycerides ; blood ; Young Adult

Objective To study the factors influencing the blood concentration of caspofungin(CPFG),construct a prediction model,and validate the predictive effect of the model,so as to provide reference for the individualised dosing of patients with fungal infections in haematology.Methods Seventy-five patients admitted to the Department of Haematology,General Hospital of Tianjin Medical University,who were treated with CPFG for antifungal therapy during the period of March 2021 to June 2022 were selected as the study subjects,and CPFG blood concentration monitoring was carried out to explore the influencing factors of CPFG blood concentration and to construct a prediction model accordingly.Hosmer-Lemeshow(H-L)was used to test the goodness-of-fit of the model,and another 30 patients were selected as the verification group,and the predictive effect of the model was verified by the receiver's operating characteristics(ROC)curve.Results The mean blood concentrations of the patients at 0.5,9 and 24 h were(12.54±4.38),(6.80±2.76),(4.13±2.16)μg·mL-1,and the mean AUC0-24h were(152.05±57.60)μg·mL-1·h.AUC0-24h was lower than the reference value(98 μg·mL-1·h)in two patients.The results of correlation analysis showed that gender showed a correlation with 0.5 h blood concentration(P＜0.05),and there was no correlation with the rest of the two time points blood concentration and AUC0-24h(P＞0.05).Body weight and albumin(Alb)concentration showed correlation with 0.5,9,24 h blood drug concentration and AUC0-24 h(P＜0.05),and the rest of the indicators showed no correlation with blood drug concentration and AUC0_24h at each time point(P＞0.05).The results of multifactorial analysis showed that the factors influencing the patients'0.5 h blood concentration were gender,Alb concentration and body weight,and the factors influencing the 9 and 24 h blood concentration and AUC0-24h were Alb concentration and body weight(P＜0.05).Correlation analysis showed that the daily dose was positively correlated with the plasma concentration of CPFG at 0.5,9 and 24 h and AUC0-24h(P＜0.05).The results of multivariate analysis showed that the daily dose was also one of the influencing factors of the plasma concentration of CPFG(P＜0.05).ROC curve shows that the model has good prediction ability.Conclusion Body weight and Alb are significantly associated with CPFG blood concentrations and area under the drug-time curve,which can be used as a basis for preventive risk avoidance.

This study was aimed to explore whether the GVHD in mice can be ameliorated and the GVL effect in mice can be reserved by transfusion of lymphocytes of donors fed with recipient splenocytes effect. Male (DBA-2) mice (H-2(d)) as donors were fed with BALB/c splenocytes, DBA-2 splenocytes, bovine serum albumin, or regular chow, every other day. Induction of tolerance was assessed by a mixed lymphocyte reaction (MLR). Female (BALB/c) mice (H-2(d)) as recipients received total body irradiation (TBI) of 6.0 Gy ((60)Cogamma-ray) followed by inoculation of 3 x 10(3) P388 mouse leukemia cells on the same day. Subsequently, tail vein injection of 2 x 10(7) splenocytes supplied by DBA-2 was undertaken. Control groups were fed identically without leukemia cell inoculation. The results showed that GVHD was significantly ameliorated and CD4(+)/CD8(+) ratio increased in recipient-mice transplanted with splenocytes of tolerated donors, compared with control animals. There was no significant difference in survival rate between different groups of recipients inoculated with leukemia cell. It is concluded that the peroral recipient-mouse splenocytes can ameliorate GVHD without hampering effect on GVL.
Adjuvants, Immunologic ; pharmacology ; Animals ; Cell Extracts ; immunology ; pharmacology ; Cell Transplantation ; Female ; Graft vs Host Disease ; immunology ; prevention & control ; Graft vs Leukemia Effect ; immunology ; Leukemia P388 ; therapy ; Lymphocytes ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred DBA ; Spleen ; cytology ; immunology ; Whole-Body Irradiation

OBJECTIVETo understand the prevalence of hypercholesterolemia, high blood low density lipoprotein cholesterol, low blood high density lipoprotein cholesterol and hypertriglyceridemia among Chinese adults in 2010.

METHODSLevels of triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) and total cholesterol (TC) were determined in fasting serum for subjects who were selected by multi-stage stratified cluster random sampling in from 162 surveillance points of 31 provinces in 2010. Prevalence of hypercholesterolemia, high blood LDL-C, low blood HDL-C and hypertriglyceridemia of 97 409 subjects was analyzed.

RESULTSAfter the complex weighting, prevalence of hypercholesterolemia in Chinese adults was 3.3%, with 2.2%, 4.7% and 4.7% in the groups of 18 - 44, 45 - 59 and over 60 years old (P < 0.01), respectively, 3.4% and 3.2% in males and females (P > 0.05), respectively, 4.2% and 2.9% in urban and rural areas (P < 0.01), 4.2%, 2.4% and 3.1% in areas of east, central and west (P < 0.01). Prevalence of high blood LDL-C was 2.1%, with 1.3%, 3.0% and 3.6% in the groups of 18 - 44, 45 - 59 and over 60 years old (P < 0.01), respectively, 2.1% in both males and females (P > 0.05), 3.0% and 1.8% in urban and rural areas (P < 0.01), and 2.9%, 1.5% and 1.8% in areas of east, central and west (P < 0.01), respectively. Prevalence of low blood HDL-C was 44.8%, with 46.9%, 42.6% and 41.2% in the groups of 18 - 44, 45 - 59 and over 60 years old (P < 0.01), 50.6% and 38.9% in males and females (P < 0.01), respectively, 45.4% and 44.6% in urban and rural areas (P < 0.05), and 43.5%, 43.3% and 48.6% in areas of east, central and west (P < 0.01). Prevalence of hypertriglyceridemia was 11.3%, with 10.1%, 14.2% and 10.8% in the groups of 18 - 44, 45 - 59 and over 60 years old (P < 0.01), respectively, 13.8% and 8.6% in males and females (P < 0.01), respectively, 12.1% and 10.9% in urban and rural areas (P < 0.01), and 11.0%, 11.7% and 11.2% in areas of east, central and west (P < 0.05).

CONCLUSIONLow blood HDL-C and hypertriglyceridemia are two major types of dyslipidemia in Chinese adults.

Adolescent ; Adult ; Age Distribution ; Asian Continental Ancestry Group ; China ; epidemiology ; Dyslipidemias ; epidemiology ; Female ; Humans ; Hypercholesterolemia ; epidemiology ; Hypertriglyceridemia ; epidemiology ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Sex Distribution ; Young Adult

In this study, HPLC-ESI-MS and HPLC methods were established to explore the differences in the main chemical components and content of Mori Cortex with(mulberry root bark) and without(Mori Cortex) the phellem layer from both qualitative and quantitative aspects. The HPLC-ESI-MS method was used for quality analysis in positive and negative ion modes, and 33 compounds were identified in mulberry root bark, 22 compounds in Mori Cortex, and 26 compounds in phellem layer; mulberry root bark and Mori Cortex shared 22 components, and mulberry root bark has 11 unique compounds; Mori Cortex and its phellem layer shared 15 components, while Mori Cortex has 7 unique compounds. HPLC method was used to simultaneously determine 7 major constituents, including mulberroside A, chlorogenic acid, dihydromorin, oxyresveratrol, moracin O, kuwanon G, and kuwanon H, and the developed method showed good linearity(r>0.998 9) within the concentration range and the recoveries varied from 99.88% to 103.0%, and the RSD was 1.7%-2.9%. The HPLC results showed that the contents of the 7 compounds have great differences in 13 batches samples, compared with mulberry root bark, the contents of mulberroside A, chlorogenic acid, dihydromorin and moracin O of Mori Cortex were increased, while the contents of oxyresveratrol, kuwanon G and kuwanon H were decreased after peeling process. These results can provide a basis for the rationality and quality control of Mori Cortex required to remove the phellem layer.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Mass Spectrometry ; Morus ; Plant Bark

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*