Objective To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) pathway in the protective effect of remifentanil or ischemic preconditioning (IPC) against hepatic ischemia-reperfusion (I/R) injury in rats.Methods One hundred and forty-four male SD rats,weighing 200-250 g,were randomly assigned into 6 group ( n =24 each):sham operation group (group S),I/R group,remifentanil group (group R),IPC group,SB203580 (a specific p38MAPK inhibitor) + remifentanil group (group SB + R),and SB + IPC group.The animals were anesthetized with intraperitoneal 20％ urethane 1 mg/kg.Partial liver ischemia was produced by clamping the hepatic pedicle supplying left lobe and middle lobe for 30 min,followed by 120 min reperfusion.In group R,remifentanil was infused intravenously at 2μg· kg- 1 · min- 1 starting from 30 min before ischemia until the end of reperfusion.In IPC group,the rats were subjected to 3 episodes of 5 min ischemia at 5 min intervals before I/R.SB203580 0.2 mg/kg was injected intravenously at 5 min before remifentanil infusion or IPC in groups SB + R and SB + IPC,and the equal volume of normal saline was given in the other groups.Six rats in each group were selected at 30,60,90 and 120 min of reperfusion and venous blood samples were taken from inferior vena cava for measurement of serum ALT and AST activities and concentrations of TNF-a and 1L-1β.The rats were then sacrificed and liver tissues were taken for microscopic examination and determination of phosphor-p38MAPK expression by Western blot.Results Compared with group S,serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased at each time point (P ＜ 0.05) and pathological injury was aggravated in group I/R.Compared with group I/R,serum AST and ALT activities and serum levels of TNF-a and IL-lβ were significantly decreased and phosphor-p38MAPK expression was up-regulated at 90 min of reperfusion in groups R and IPC ( P ＜ 0.05).The serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased,phosphor-p38MAPK expression was down-regulated at 90 min of reperfusion ( P ＜ 0.05),and pathological injury was aggravated in group SB + R compared with group R,and in group SB + IPC compared with group IPC.Conclusion Activation of p38MAPK pathway and inhibition of inflammatory response may be involved in the mechanism by which remifentanil or IPC reduces the hepatic I/R injury in rats.

Adenomatoid Tumor ; metabolism ; pathology ; surgery ; Adult ; Biomarkers, Tumor ; metabolism ; Female ; Humans ; Hysterectomy ; methods ; Keratins ; metabolism ; Lymphangioma ; pathology ; Uterine Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Objective:To explore and analyze the points-selection rules in acupuncture treatment of mammary gland hyperplasia (MGH) by data mining and statistical method. Methods:Clinical literatures about the treatment of MGH with acupuncture published in the recent 16 years were retrieved from Chinese Journal Full-text Database (CJFD) and established into a database by Excel. The SPSS 20 version software and Clementine 12.0 version software were adopted to analyze the frequency and association rules of points-selection in the treatment of MGH with acupuncture. Results:The top 3 points used most frequently in acupuncture treatment of MGH were Danzhong (CV 17), Taichong (LR 3) and Zusanli (ST 36); points from the Stomach Meridian of Foot Yangming and Liver Meridian of Foot Jueyin were most commonly used; the commonly selected points were predominantly distributed in thoracic and abdominal regions and lower limbs; emphasis on the combination use of local and distal points; of the specific points, the five Shu-Transmitting points were mostly used; association analysis showed that the associations among Taichong (LR 3), Danzhong (CV 17) and Zusanli (ST 36) were the most significant. Conclusion: The data mining results substantially accord with the general rules of acupuncture-moxibustion theories in traditional Chinese medicine, able to reflect the points-selection principles and features in acupuncture treatment of MGH and provide evidence for the points selection in the treatment of MGH in acupuncture clinic.

According to the requirements of the regulatory authorities, degree of modification (DP) should be included in the characterisation of the PEGylated protein drug substance, and is one of the critical quality attributes for quality control. In this study, based on the fundamental assumption that the refractive index (RI) signal and the ultraviolet (UV) signal of PEGylated protein are equal to the sum of the corresponding signal produced by the polyethylene glycol (PEG) and protein parts of the conjugates in their uncoupled state, we developed a method to determine the DP of PEGylated recombinant human growth hormone (inpegsomatropin). In this method, 20 μL of 1 mg·mL^-1 human growth hormone (hGH) standard, 2 mg·mL^-1 PEG reference substance and 1 mg·mL^-1 drug substance solution were each injected to size exclusion chromatographic (SEC) column for separation, detected with ultraviolet and refractive index (UV-RI) detectors in series. Finally, the DP was calculated as the formula derived from the fundamental assumption. The developed SEC-UV-RI method showed good specificity, repeatability (RSD = 0.63%, n = 9) and accuracy, with a recovery of 100.0%, compared with the result obtained from the simultaneously established classical acid hydrolysis method, demonstrating pretty handleability and accessibility, and is appropriate for quality control test of DP for this drug substance.

Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS.
Anti-Inflammatory Agents ; pharmacology ; Carthamus tinctorius ; Computational Biology ; Drugs, Chinese Herbal ; pharmacology ; Fibrinolytic Agents ; pharmacology ; Humans ; Inflammation ; drug therapy ; Medicine, Chinese Traditional

Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.

OBJECTIVETo observe the curative effects of bone marrow stem cell (BMSC) and peripheral blood stem cell (PBSC) transplantations on the avascular necrosis of femoral head (ANFH).

METHODSTotally 122 ANFH patients (211 coxae) treated by BMSC or PBSC transplantations were enrolled from July 2004 to December 2006. All of them were classed to different stages according to the ARCO. Control group were desired as themselves before and after treatment. The puncture of femoral artery was conducted with digital subtraction angiography (DSA), and the tubes were inserted into medial femoral circumflex artery, lateral femoral circumflex artery and obturator artery with the cell suspensions were gradually poured into the arteries.

RESULTSThe joint pain, joint functions and walking distance of 122 patients were detected for the follow-up. Compared with before treatment, the calibers thickened; vessels increased and blood velocity quickened of femoral head blood-supply artery were observed in 15 patients after 6 months checked by DSA. The reduced areas of femoral head necrosis in 8 patients indicated the new bone formation between 12 and 24 months.

CONCLUSIONSAutologous BMSC and PBSC transplantation results in the new bone formation and improvement of ischemia in areas of femoral head necrosis at 6 months. The change of angiography was observed about 12 to 24 months after cell transplantation. The stem cell transplantation is convenient, safe and effective in the treatment of the ANFH with no adverse reaction, and can be considered as a new therapy of ANFH.

Bone Marrow Transplantation ; Femur Head ; blood supply ; pathology ; surgery ; Femur Head Necrosis ; surgery ; Follow-Up Studies ; Humans ; Ischemia ; surgery ; Peripheral Blood Stem Cell Transplantation ; Stem Cell Transplantation ; methods ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVETo summarize the detailed failure mechanisms of revision hip arthroplasties and related risk factors.

METHODSFrom November 1988 to July 2008 revision of total hip arthroplasties was performed in 327 patients. The medical history, clinical and imaging material and operation records were investigated.

RESULTSRegarding revision as the end point of the study, the reasons for 327 revision arthroplasties were aseptic loosening in 226 hips (69.1%), infection in 52 hips (15.9%), periprosthetic fracture in 22 hips (6.7%), instability in 17 hips (5.2%), stem fracture in 5 hips (1.5%) and liner dissociation in 5 hips (1.5%).

CONCLUSIONSThe main failure mechanisms of primary hip arthroplasties are aseptic loosening and infection of implants, which could be attributed to improper selection of operation indications and implants and limitations to surgical philosophy and technique.

Adult ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Periprosthetic Fractures ; Prosthesis Failure ; Reoperation ; Retrospective Studies ; Risk Factors ; Surgical Wound Infection ; Treatment Failure

BACKGROUNDThe mechanisms of action of volatile anesthetics are still unknown. Recently, the use of genetics as a means to investigate anesthetic action has increased in scale. However, only limited forward genetic approach studies were performed in mammals, especially with volatile anesthetics as the selection agent. In the present study, a selective breeding process was designed to produce strains of mice with different sensitivity to isoflurane.

METHODSOne hundred and sixty male and female virgin outbred ICR/CD-1 mice at 65 - 70 days of age were selected as original generation, and the median effective dose (ED(50)) of inhaled isoflurane were measured by probit analysis with the loss of righting reflex as the endpoint of anesthesia. The most sensitive males and females were selected and mated one another randomly, as with the most resistant males and females. Thus two branches of mice (sensitive and resistant to isoflurane) were created and allowed to produce the next generation. At 65 - 70 days of age, screening experiment was performed in offspring, by selecting the most sensitive mice in sensitive branch and the most resistant mice in resistant branch. Selected males and females within each branch were mated one another randomly to produce the following generation. The same procedure was performed in the offspring. The process of screening and breeding was repeated for 8 generations, and then strains were conserved by mating the offspring one another randomly within each branch for 3 generations. Each pair of mice was allowed to produce the second litters as a backup, and isoflurane ED(50) was measured in mice from the second litters.

RESULTSIsoflurane righting reflex ED(50)s (95% confidence limit (CL)) in original mice were 0.65% (0.58% - 0.72%) in females and 0.63% (0.56% - 0.69%) in males. After the 4th generation, isoflurane ED(50)s in resistant branch were significantly higher than those in sensitive branch (P < 0.05), for both in females and males. In the 11th generation, isoflurane ED(50) in the two branches differed by 32% in females and 36% in males.

CONCLUSIONSAfter 8 generations of selective breeding and 3 generations of strain conservation, two strains of mice with high and low sensitivity to isoflurane were developed. The separation of inhaled anesthetic requirement in parents could be transferred to the offspring in mice.

Anesthetics, Inhalation ; therapeutic use ; Animals ; Breeding ; methods ; Female ; Isoflurane ; therapeutic use ; Male ; Mice ; Mice, Inbred ICR ; Reflex ; drug effects ; Selection, Genetic ; genetics

OBJECTIVETo study the distribution and quantity of CD44+/CD24- cells in breast cancer tissue and the cell lines, and as well as its correlation with the expression of various breast cancer markers and molecular subtyping of breast carcinoma.

METHODSThe expression of CD44/CD24, estrogen receptor, progesterone receptor, HER2, human estrogen-induced protein PS2, bcl-2 and nm23 in 60 cases of invasive ductal carcinoma of breast were studied by either single or double immunohistochemical staining. The co-expression of CD44 and CD24 in 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231) was also examined.

RESULTSThe quantity and distribution of CD44+/CD24- cells varied greatly and no specific patterns were identified. The percentage of CD44+/CD24- in breast cancer was 65%. The amount of CD44+/CD24- cells did not correlate with the age of patients, lymph node metastasis, tumor size, molecular subtypes and expression of various breast cancer markers in breast carcinoma. The proportion of CD44+/CD24- cells in MCF-7, MDA-MB-468, and MDA-MB-231 cell lines was <1%, 5% and >80%, respectively.

CONCLUSIONSCD44+/CD24- cells are demonstrated in certain breast cancer tissues and cell lines. However, there is no relationship obtained between the quantity or the distribution of these cells and the molecular subtyping or the clinicopathologic parameters in breast cancer.

Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms ; classification ; metabolism ; pathology ; CD24 Antigen ; metabolism ; Carcinoma, Ductal, Breast ; classification ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Lymphatic Metastasis ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Progesterone ; metabolism ; Trefoil Factor-1 ; Tumor Suppressor Proteins ; metabolism