Tumor multidrug resistance (MDR) is the leading cause of clinical chemotherapy failure and death.Researches show that the occurrence of MDR is related to P-glycoprotein,multidrug resistance-associated proteins,breast cancer resistance-associated proteins,lung resistance-related proteins and other factors.Now the reversal strategies of MDR include chemical drugs reversal,gene reversal,immune reversal,traditional Chinese medicine reversal and drug-loaded nano-system reversal,which make some progress and help to improve the effect of cancer chemotherapy.

Protein kinase C (PKC) is a group of phospholipid-dependent serine/threonine protein kinases, which togeth-er with protein kinase A (PKA) and protein kinase G (PKG) constitute a superfamily of serine/threonine protein kinase AGC. PKC includes classic PKC, novel PKC, atypical PKC and some members of kinase associated with PKC (PRK). PKC is wide-ly distributed in mammalian tissues and cells, which plays an important biological role in growth and metabolism, prolifera-tion and differentiation of cells. A series of studies have demonstrated that variations of multiple cells, occurrence and devel-opment of diseases are related to the abnormal expression of PKC. Therefore, designing and searching for efficient PKC inhib-itors have very important implications for synthesis of many kinds of effective drugs and treatment of a variety of clinical dis-eases including cancer, cardiovascular, and hypertension, et al. In recent years, the research on PKC inhibitors has become the focus of domestic and foreign research. A large number of literatures have reported many kinds of effective PKC inhibi-tors, and analyzed their function site, mechanism, clinical trial data and so on. The discovery of these PKC inhibitors has im-portant implications for structural analysis of PKC and the treatment of diseases. So in this paper, the efficient PKC inhibi-tors are summarized.

Objective To investigate the effect of experimental benzolism on marrow eryghrocyte micromucleus.Methods Fifty male KunMingmice(KM)were randomly divided into 5 groups:one control group and four experimental groups with 10 mice in each group.The mice were injected subcutaneously with sodium chloride in control group and benzene in experimental groups on every Monday,Wednesday and Friday for four weeks.Four experimental groups were injected with a dosage of 0.5 ml/kg(group B1),1.0 nd/kg(group B2),1.5 ml/kg(group B3) and 2.0 ml/ks(group B4),respectively.Before and after injection of sodium chloride or benzene weekly.weight was measured,and the alteration of erythrocyte micronucleus in peripheral blood and marrow were detected.Results ① Compared to the control group,several indices were partly changed in B1 and B2 groups,while all indices changed significantly in group B3 and B4 groups four weeks after injection(P<0.01).②The erythrocyte micronucleus rate of experimental mice in peripheral blood and marrow showed ascending tendency with the extension of benzene injection phase,peak emerged in the third week and decreased in the fourth week.③In the 4th week,compared to the control group,the alteration of erythrocyte micronucleus in marrow in all experimental groups were significantly increaged(P<0.05).Conclusions Benzolism may induce the increasing of micronucleus rate of mature erythrocyte in peripheral blood and erythrocyte in marrow.which can be used to detect status of being restrained in marrow erythrocyte series.

BACKGROUND: The skill to culture osteoblasts primarily has been well developed. However, trypsinase can affect membrane protein of osteoblasts if the time of digestion is long. Therefore, it is of great significance to select an ideal method to avoid the damage from trypsinase to cells as possible when culturing osteoblasts.OBJECTIVE: To explore a novel method to isolate and culture SD rat osteoblasts in vitro, and identify the functions of the cells.DESIGN: Observational study.SETTING: Department of Orthopaedics, First Affiliated Hospital of Jinan University.MATERIALS: This experiment was carried out in the Department of Orthopaedics, First Affiliated Hospital of Jinan University from March to May in 2007. Eight SPF 24-hour old SD rats were used in the experiment. The rats, irrespective of gender, were provided by the Experimental Animal Center of Nanfang Medical University. The experimental animals were disposed according to ethical criteria. The main reagents were detailed as follows: collagenase Ⅱ (Sigma Company);trypsin (Sigma Company); alkaline phosphatase (ALP) kit (Nanjing Jiancheng Biological Products Company); SABC-1021(Wuhan Boster Biotechnology Company).METHODS: 24-hour old SD rats were chosen for experiment. The newly born SD rats were sacrificed by anesthesia and the cranial bones of the rats were obtained cleanly, erased completely of the periosteum and cut to blocks of I mm3. The cranial bones were digested by 0.25 % trypsinase for 20 minutes, then by 0. 1% type Ⅱ collagenase for 60 minutes. The digestive time of trypsinase was controlled in the process of digestion to avoid to harm the cells. The liquid was gathered and centrifuged. The cells were cultured in culture flask and were purified by many times adhered.MAIN OUTCOME MEASURES: Morphology observations under the inverted phase contrast microscope, transmission electron microscope, and scanning electron microscope were performed. The phenotype, calcium tuberculation and the expression of alkaline phosphatase were studied with alizarin red staining and modified Gomori Ca-Co assays respectively.The cells were also evaluated with collage Ⅰ immunohistochemical staining.RESULTS: The cultured cells had active proliferation ability. Cells showed multi-angle or fusiform shape. Nucleus was immature and organell was plentiful. Therefore, they had typical morphological characters of osteoblasts. Moreover, they showed the osteoblastic phenotypes such as their synthesis of alkaline phosphatase, collage Ⅰ and formation of calcium tuberculations.CONCLUSION: The cells cultured by our modified enzymatic digestion method had typical morphological and biological characteristics of osteoblasts.

Objective To study the effect of lung cancer prevention in Baoji city, one of the cities with high lung cancer morbidity in China. Methods To investigate the mortality of lung cancer from 1992 to 1996 in Baoji and compare it with the data of Baoji in 1970s and the current data in whole China. Information of lung cancer pa- tients was collected from the Malignant Tunout Monitoring Station in Baoji. To investigate by sampling survey the status of smoking of Baoji population based on the principle of clustering random sampling. Information about air pollution in 1980s and 1990s was obtained from the Environmental Monitoring Station in Baoji. ResultsComparing with 1970s, the crude mortality rates of lung cancer in Baoji in 1992～ 1996 increased both in males and females,but the range was narrower than that in whole China. Ajusted mortality rates of lung cancer didn＇t change in females but decreased in males. However, either crude or adjusted mortality rate was lower than the average level of the whole country. The status of air pollution has been improved dramatically since the early 1980s in Baoji. So far, except to- tal suspended particles (TSP), NOx and SO2 levels have reached the Criteria of Air Quality of China. But the smoking rate was still higher. ConclusionThe prevention of lung cancer in Baoji is effective, but the role of measures needs further study. Baoji should not be considered as a city with high lung cancer morbidity in our country at present.

BACKGROUND: The structure of nanometer chitosan-sodium/collagen (nano-CS/COL) is similar to that of the extracellular matrix (ECM) in the nanometer level. Whether this can promote the adhesion and growth of bone marrow mesenchymal stem cells (MSCs) and the calcification?OBJECTIVE: To investigate the in vitro histocompatibility of nano-CS/COL. DESIGN: Single sample observation.SETTING: Department of Orthopaedics, First Hospital, Jinan University. MATERIALS: This study was performed at the Experimental Center, First Hospital Affiliated to Jinan University between March 2007 and July 2007. Ten 4-week-old female SD rats, of SPF grade, weighing 200 g, were provided by the Guangdong Provincial Laboratory Center [Permission No. SCXK (yue) 2003-0002]. The protocol was carried out in accordance with animal ethics guidelines for the use and care of animals. Nano-CS/COL METHODS: Bone marrow MSCs were isolated from SD rats and cultured. Cell surface antigen was detected by loss cellanalyticalmethod.Nano-CS/COLscaffold waspreparedbypolyelectrolyte confocallaser-scanning microscopy. The well-grown cells of the third passage were co-cultured in vitro on the nano-CS/COL scaffold. Taking simple nano-CS/COL scaffold material as control, the histocompatibility of scaffold material and cells were comprehensively evaluated by cell adherence rate, growth curve, cell activity and cycle, and scanning electron microscope observation.MAIN OUTCOME MEASURES: ① Identification of cell surface antigen marker after isolation and culture of bone marrow MSCs. ②The histocompatibility of nano-CS/COL material and bone marrow MSCs 2, 4 and 8 days after nano-CS/COL material compounded with cells. ③Determination of adherence rate of cells to nano-CS/COL material. ? Cell circle and activity detected 5 days after nano-CS/COL material compounding with cells. RESULTS: ① Detection results of cell surface antigen marker: The expression of CD29, CD106, CD44, CD34 and CD45 was 90.86%, 73.38%, 82.61%, 0.76% and 0.60%, respectively. ②Histocompatibility of bone marrow MSCs and nano-CS/COL material: It was shown under the scanning electron microscope that nano-CS/COL scaffold presented porous three-dimensional structure, and different sizes of macropoles and interconnected small pores. The interval porosity determined by quality assay was 85%-90%, and aperture averaged 150 μm (range 50 - 300u m). Two days after bone marrow MSCs compounded to nano-CS/COL scaffold, bone marrow MSCs presented globular shape and were scattered; Four days later, bone marrow MSCs presented shuttle shape, extended and anchored on the surface of nano-CS/COL by pseudopods; Eight days later, bone marrow MSCs proliferated and fused each other, and they secreted a lot of extracellular matrix, then which covered most material particles. ③ The adherence rate of bone marrow MSCs to nano-CS/COL: Bone marrow MSCs and nano-CS/COL were co-cultured 2 and 6 hours separately. The adherence rate of bone marrow MSCs was higher to nano-CS/COL scaffold than to simple chitosan scaffold. ④ Comparison of cells and cell cycle between on nano-CS/COL scaffold and on the chitosan scaffold: On the nano-CS/COL scaffold, cell activity was 96.67%, cell cycle at G0-G1 was 90.81%, at G2-M was 0.52% and at S was 8.66%. G2/G1 was 1.81. On the simple chitosan scaffold, cell activity was 95.27%, cell cycle at G0-G1 was 87.14%, at G2-M was 9.69%, and at S was 4.16%. G2/G1 was 1.80.CONCLUSION: Nano-CS/COL scaffold can be used as tissue engineering biomaterials because bone marrow MSCs can well grow on it.

Objective To analyze the medication rules of Professor LAO Shaoxian in the treatment of gastric stuffiness based on syndrome differentiation.Methods The effective prescriptions for patients with gastric stuffiness treated by Professor LAO Shaoxian from March 2017 to March 2022 were collected,and the general information,chief complaints,diagnosis,syndrome differentiation and prescriptions of patients were extracted.Excel software and the ancient and modern medical records cloud platform(V 2.3.7)were used to construct the prescription database.Data mining function was used to carry out analysis of the syndrome type of prescription,analysis of the frequency and property of Chinese herbs,as well as association rule analysis and cluster analysis.Results A total of 272 prescriptions were included,involving 164 kinds of medicinal herbs.The main traditional Chinese medicine(TCM)syndrome types are damp-heat syndrome and qi stagnation syndrome.The frequency of 25 herbs was more than or equal to 30 times.The representative herbs is Pinellinae Rhizoma Praeparatum,Glycyrrhizae Radix et Rhizoma,Citri Reticulatae Pericarpium,Perillae Caulis and Aucklandiae Radix.The medicinal properties are mainly warm and flat.The medicinal flavors are spicy,bitter and sweet.The drug meridians mainly included the spleen,stomach and lung meridians,followed by the liver meridian.There were 23 core drug pairs obtained by association rules,such as"Aucklandiae Radix-Perillae Caulis","Citri Reticulatae Pericarpium-Perillae Caulis",and"Pinellinae Rhizoma Praeparatum-Citri Reticulatae Pericarpium".Clustering analysis of drugs can be divided into three combinations,which have the effects of regulating qi and relieving distension,resolving dampness,and clearing heat and detoxifying.Conclusion The core prescription of Professor LAO Shaoxian in the treatment of gastric stuffiness is Aucklandiae Radix,Perillae Caulis,Citri Reticulatae Pericarpium,Pinellinae Rhizoma Praeparatum,Glycyrrhizae Radix et Rhizoma,Kaki Calyx,Aurantii Fructus Immaturus and Arecae Pericarpium.It focuses on regulating qi movement of middle jiao and treating spleen and stomach simultaneously.The main therapeutic method is regulating qi and relieving distension.At the same time,attention should be paid to the application of dampness-dispelling and stagnation-removing,heat-clearing and detoxifying drugs.The clinical therapy of Professor LAO Shaoxian on gastric stuffiness is significant,which can be used as a reference for diagnosis and treatment.

The relative bioavailability of roxithromycin dispersive tablet in healthy volunteers was evaluated in this study. Its concentration in plasma was detected by high performance liquid chromatography (HPLC) after twenty healthy male volunteers were given each a single dose of 300 mg roxithromycin. The experiment data were obtained using DAS programme. The values of Cmax were 10.16+/-1.46 and 10.34+/-1.66 microg x ml(-1) at 2.33+/-0.61 and 2.28+/-0.62 h respectively; of t1/2 were 9.00+/-1.58 and 8.68+/-1.66 h respectively; of AUC0-->Tn were 143.32 +/-25. 80 and 138.93+/-22. 49 microg x h x ml(-1) respectively; of AUC0-->infinity were 158.63+/-26.86 and 153.77+/-24.75 microg x h x ml(-1) for test and reference drugs. Relative bioavailability of the tested roxithromycin was 103.63%+/-14.04%. The result showed that the two dispersive tablets are bioequivalent.
Administration, Oral ; Anti-Bacterial Agents ; blood ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; Humans ; Male ; Roxithromycin ; blood ; pharmacokinetics ; Tablets ; Therapeutic Equivalency ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).

METHODSPatients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.

RESULTSA total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).

CONCLUSIONAnagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.

Humans ; Hydroxyurea ; administration & dosage ; therapeutic use ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Platelet Count ; Quinazolines ; administration & dosage ; therapeutic use ; Thrombocythemia, Essential ; drug therapy ; Treatment Outcome