Volume 87  ·   Issue 10  ·  2007

"Everything in the biological world follows the laws of mechanics from the constituent molecules to the organic whole", Professor Feng Yuanjian, the father of contemporary biomechanics, wrote in his work on biomechanics. Professor Feng began to study biomechanics in the 1950s. Because of his outstanding contributions to biomechanics, especially his major discoveries in cardiovascular biomechanics, he is praised as the father of contemporary biomechanics. He is the only scientist who has been awarded academicians of the three American academies (Academy of Sciences, College of Engineering and College of Medicine) and academicians of the Chinese Academy of Sciences [1].

The incidence of chronic constipation (CC) increases gradually with the changes of dietary structure, disease spectrum and the influence of psychological and social factors on the disease. The prevalence of constipation in adults in China is 3% ~17% [1-2].

In recent years, neoadjuvant chemotherapy (NCT) has become a hot spot in the treatment of breast cancer [1-2]. In 1970s, the Institute of cancer in Milan, Italy, was first used for the treatment of inoperable locally advanced breast cancer (LABC), and obtained a relatively good curative effect. Some unresectable breast cancer became resectable after chemotherapy.

Objective to evaluate the efficacy of combined drug therapy on patients with severe constipation of Hirschsprung colon, and to provide reference for non-surgical treatment.Methods A retrospective study was conducted on 10 patients with severe constipation of Hirschsprung colon who visited the Department of Internal Medicine of Peking Union Medical College Hospital of China Union Medical Sciences University, Chinese Academy of Medical Sciences from February 2005 to April 2006. There were 4 and 6 males and 6 females, respectively, with an average age of 38 years and an average course of 10 years. Surgical or conventional medical treatment was ineffective, and Hirschsprung colon was confirmed by barium enema. Five patients had colonic obstruction at the time of visit. Maintenance therapy continued with the combination of the above drugs, and the dose was reduced after the condition was relieved. If there was fecal impaction in the rectum, intestinal washing or enema was given. The frequency of defecation, stool characteristics, difficulty of defecation, abdominal symptoms (abdominal pain, abdominal distension and vomiting), complications and side effects of intestinal obstruction were observed. Results Among 10 patients, 1 case was postoperative for Hirschsprung's disease. A case of postoperative congenital anorectal malformation; Secondary to chronic constipation in 3 cases; Secondary to diabetic neuropathy: 1 case; Four cases of chronic pseudo-colonic obstruction were followed up for 1 to 7 months, and their condition was stable, without complications of intestinal obstruction. The dilatation degree of colonic lumen was significantly improved in 7 cases, the fluid-gas level disappeared in 5 cases of intestinal obstruction, and mild diarrhea disappeared in 2 cases after drug reduction. Conclusion the combination of tegaserod maleate, polyethylene glycol 4000 and Liuwei Anxiao can effectively relieve the symptoms, control the complications of intestinal obstruction, effectively prevent recurrence and delay surgery in the short term.

Objective to study the effects of octapeptide cholecystokinin (CCK-8) on intracellular calcium release and extracellular calcium influx in rat gastric antrum smooth muscle cells (SMC) and to explore the specific related mechanisms. Methods (1) The contraction activity of isolated rat gastric antrum muscle strips under different conditions was recorded by multi-channel physiological recorder; (2) Immunoblotting and immunoprecipitation were used to detect inositol 1,4,5-triphosphate type 3 receptor (Ins P3R3) and its phosphorylation level in gastric antrum SMC; (3) The effect of CCK-8S on intracellular calcium ion concentration ([Ca2+] i) was observed by Fura-2/AM labeling of gastric antrum SMC; (4) The changes of L-type voltage-gated calcium channel current (ICa-L) in gastric antrum SMC were detected by whole cell patch clamp. Results (1) The contraction amplitude and frequency of gastric antrum muscle strips were significantly changed under the action of CCK-8S [the growth rates were (62±13) % and (58±17) %, respectively, both P<0.01], which could be blocked by CCK-A receptor antagonists and calcium pump inhibitors; (2) Protein kinase C (PKC) upregulated the phosphorylation level of InsP3R3 and inhibited CCK-8S-mediated intracalcium release; (3) The significant increase of [Ca2+] i caused by CCK-8S [from (69±7) mol/L to (472±36) nmol/L, P<0.01] was blocked by CCK-A receptor or intracellular calcium pump inhibitor and PKC agonist, respectively; CCK-8S can still cause the increase of [Ca2+] i when exocalcium is removed or L-type calcium channel blockers are administered; (4) CCK-8S significantly enhanced ICa-L in antral SMC [increased from (-56±7) pA to (-89±6) pA, P<0.01], which could be blocked by ICa-L blockers, intracellular calcium pump inhibitors and calcium-dependent chloride channel blockers, respectively.Conclusion CCK-8S-induced increase of [Ca2+] i in rat antral SMC depends on intracellular calcium release regulated by PKC-mediated InsP3R3 phosphorylation.Intracellular calcium release can activate ICl-Ca, induce cell membrane depolarization, activate ICa-L, induce extracellular calcium influx, and finally induce SMC contraction.

Objective to study the effect of small intestinal electrical stimulation on human small intestinal transmission function. Methods A nasogastric tube with ring electrode was implanted into the duodenum by gastroscope in 12 healthy subjects, and 99Tcm of non-absorbable electrolyte balance solution was injected into the gastric tube. The time of radionuclide reaching ileocecal region after real or pseudo small intestinal electrical stimulation was measured, and the severity of dyspepsia in the experiment was evaluated. Results (1) The time of radionuclide reaching ileocecal region during real small intestinal electrical stimulation was (28±10) min, which was significantly lower than that in pseudo small intestinal electrical stimulation group [(39±17) min, P<0.05]. (2) There was no significant difference between volunteers' conscious symptom scores before and after real stimulation (median 1.0 vs 1.5, P>0.05), nor was there any significant difference between true stimulation and pseudo stimulation (median conscious symptom score 0.5) (P>0.05). Conclusion Small intestinal electrical stimulation can accelerate small intestinal transmission without causing dyspepsia, which may become a new treatment for small intestinal motility disorders

Objective to establish the normal defecation frequency and the prevalence of functional bowel disease among urban primary and secondary school students in China.Methods 51,956 primary and secondary school students in 6 provinces and two municipalities directly under the Central Government were investigated by a multi-level cluster random sampling method.Results ①88.05% ± 0.28% of students had a defecation frequency of 1~2 times a day or 1 time every 2 days.The defecation frequency of girls was significantly less than that of boys.The difference between the two was statistically significant (P<0.01); ②The prevalence rates of irritable bowel syndrome (IBS), functional constipation and diarrhea in urban primary and secondary school students were 20.19% (10 490), 25.92% (13 467) and 8.77% (4557) respectively. Conclusion ①The normal defecation frequency of urban primary and secondary school students was between 1~2 times a day or once every 2 days; ②IBS, functional constipation and diarrhea are common and frequently occurring diseases among urban primary and secondary school students.

Objective to use superparamagnetic iron oxide (SPIO) as a marker of magnetic resonance tracer cells to provide experimental evidence for vascular endothelial progenitor cell transplantation to prevent and treat vascular endothelial injury diseases.Methods Peripheral blood vascular endothelial progenitor cells (EPCs) of New Zealand white rabbits were isolated, identified and cultured, and Fe2O3-poly-L-lysine (PLL) was prepared and EPCs were labeled in vitro.The right carotid artery of rabbits was dilated with 2.5 F balloon to make a model of intimal injury, and EPCs were local transplanted.Five rabbits in group A were transplanted with Fe2O3-PLL labeled EPCs, five rabbits in group B were transplanted with fluorescent labeled EPCs, and five rabbits in group C were blank controls.7 days after cell transplantation, all rabbits underwent MR carotid artery scanning, and the injured blood vessels were taken for histopathological examination, and the changes of MR signal were compared with the changes of MR signal.Results the labeling rate of Fe2O3-PLL in EPCs was>95%. 7 days after cell transplantation, MR scan T2WI showed obvious low signal area in the injured blood vessel wall, while that in group B and C The pathological examination showed that there were positive cells adhering to injured vascular endothelium in group A, strong fluorescence expression in injured vascular endothelium in group B, and no expression in injured vascular endothelium in group C. Conclusion In vivo imaging with 1.5 TMR apparatus can trace and detect the homing, adhesion and distribution of magnetic particle-labeled vascular endothelial progenitor cells in injured vascular endothelium, which provides experimental basis for the prevention and treatment of vascular endothelial injury diseases by transplantation of vascular endothelial progenitor cells.

Objective to investigate the feasibility of the contrast agent folate-PL-Gd-DTPA, which can target folate receptor-positive tumor cells by MR tumor targeting, and to investigate the feasibility of the contrast agent in the diagnosis of human lung cancer in nude mice. Methods (1) The macromolecular carrier PL-DTPA was obtained after poly-L-Lysine (PL) was modified by diethylenetriamine pentaacid (DTPA) under alkaline conditions. The macromolecular contrast agent PL-Gd-DTPA was prepared by loading Gd3+. (2) The purity of macromolecules was determined by high performance liquid chromatography (HPLC), the content of Gd3+ was determined by high frequency inductively coupled plasma emission spectroscopy (ICP-AES), and the activity of the reagent was confirmed by competitive binding of cellular folate receptor. (3) The animals were divided into two groups by MR imaging in nude mice model of human lung adenocarcinoma. After plain MR scanning, MR scanning was performed at 0.5, 3, 6, 14, 24, 38, 48, 62 and 72 h after folate-PL-GD-DTPA and Gd-DTPA reagents were injected into the tail vein of rats, respectively. The signal intensity of tumor and muscle at each time point was measured. Results (1) The high purity folate-PL-GD-DTPA was prepared. The multimer had high affinity binding property to folate receptor, and the contrast agent carried 56 Gd3+ ions per molecule. (2) In the in vivo MR imaging of tumor model, the signal value of tumor at each scanning time point was statistically significant (F =7.82, P =0.0052), and the average enhancement rate was 125.4%. (3) The experimental tumor group The peak of enhancement appeared at 0.5 h time point, and there was no significant difference in muscle signal values at each scan time point in the experimental group (F =1.86, P =0.0579). Conclusion Folate-PL-Gd-DTPA can bind to folate receptor with high affinity, and can target folate receptor-positive tumors in vivo, so as to achieve MR targeted diagnosis.

Objective to explore the application of Meek micro-skin grafting (M method) in wounds. Methods The M method was used in 9 cases of burn and 1 case of necrotizing fasciitis. The area of skin grafting by M method was 2% ~28%, including 23% TBSA and 5% donor area of abdominal wall in 1 case, with an average area of 8.6%, and 4 cases were grafted with this method immediately after scabbing. 4 cases were grafted by M method on the 4th to 16th day after scabbing; Two cases of granulation wounds formed on the 35th to 45th day after injury were grafted by M method; In the M method, 42 sheets of 1:4, 40 sheets of 1:6 and 26 sheets of 1:9 gauze were applied. Simultaneously with the M method, 5 cases of artificial stamp skin grafting, 4 cases of microparticle skin grafting and 1 case of reticular skin grafting were performed on the same individual. Results the operation time of the cases with M method was 9~60 min; 8 cases survived 100%, 1 case survived 80% and 1 case survived 50%, with an average of 93%; The survival rate of other skin grafting methods was 30~240 min, and the survival rate was 100% in 2 cases, 90% ~98% in 4 cases, 80% in 3 cases, and 50% in 1 case, with an average of 86%. Conclusion Meek skin grafting is suitable for any kind of wound on the body surface (except bone exposed wound), especially for patients with large area burn; The epithelialization time of wound skin is short; According to the size of the wound surface, different proportions of expansion gauze are selected, so the amount of skin is small; Shortened surgical time; The labor intensity of staff is reduced.

Objective to investigate the expression of stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 in non-Hodgkin lymphoma (NHL) and their relationship with NHL tumor invasion. Methods The expression of SDF-1 α in lymph node and bone marrow stromal cells was detected by reverse transcription polymerase chain reaction (RT-PCR), and the expression of CXCR4 receptor in lymph node and bone marrow was detected by flow cytometry. The chemotaxis of lymphoma cells to recombinant human SDF-1 α (rhSDF-1 α) in vitro was detected by Transwell microwell isolation chamber assay. Results The expression of CXCR4 receptor on the surface of bone marrow mononuclear cells of NHL patients with bone marrow invasion and non-bone marrow invasion was significantly higher than that of normal bone marrow (84.10±12.12, 72.76±8.73 and 33.20±7.73, P<0.01), and the expression of CXCR4 in lymph node-derived lymphoma cells of NHL patients was also significantly higher than that of reactive proliferative lymphadenitis patients ( And the expression of SDF-1 α in lymph node stromal cells of NHL patients was higher than that of reactive proliferative lymphadenitis patients (P<0.01). Chemotaxis experiments showed that the mononuclear cells of lymph node and bone marrow from three different sources of NHL patients could react to rhSDF-1 α, and anti-CXCR4 monoclonal antibody could significantly inhibit the migration of these cells. Conclusion the biological axis of SDF-1/CXCR4 is an important mechanism mediating NHL tumor invasion, and the high expression of CXCR4 on the surface of lymphoma cells and SDF-1 on the site of lymphoma metastasis is closely related to the metastasis and invasion of NHL tumor cells.

Objective to investigate the correlation between CD40-E1SNP (-1C/T) and CD40-E4SNP gene polymorphisms and susceptibility to acute coronary syndrome (ACS) in Chinese Han population. Methods PCR-RFLP and DNA sequencing were used to detect the genotypes and allele frequencies of CD40-E1SNP (-1C/T) and CD40-E4SNP in 160 patients with ACS confirmed by coronary angiography and 92 patients with negative coronary angiography. The differences of CD40 genotypes and allele frequencies in the two groups were analyzed, and the effects of CD40 gene polymorphism, hypertension and diabetes on ACS were analyzed by Logistic regression model. Results the frequencies of CD40-1 allele C were 0.606 and 0.489, and the frequencies of T allele were 0.394 and 0.511, respectively, in ACS group and control group, and the differences between the two groups were statistically significant (P<0.05). The frequency of CC genotype in ACS patients (0.281) was significantly higher than that in the control group (0.130), and the difference was statistically significant (P<0.01); C allele significantly increased the risk of ACS (OR =1.608, 95% CI: 1.12-2.32, P =0.011); After adjusting age, sex and body mass index, Logistic regression analysis of CD40 gene and its harmful effects on ACS was conducted. The OR value of C allele alone was 1.608 (95% confidence interval: 1.12-2.32, P<0.05), the OR value of C allele with hypertension was 5.71 (95% confidence interval: 1.12-29.08, P<0.05), the OR value of C allele with no diabetes was 1.44 (95% confidence interval: 1.12-5.13, P<0.01), and the OR value of C allele with diabetes was 2.35 (95% confidence interval: 1.47-4.82, P<0.01). No CD40-E4SNP polymorphism was detected. Conclusion CD40-1C/T gene polymorphism is correlated with ACS. The risk of ACS was significantly increased in C allele carriers with hypertension and diabetes, but CD40-E4SNP polymorphism may not exist in Han population.

Objective to observe the long-term effect and safety of autologous bone marrow mononuclear cells (BMMC) transplantation through coronary artery in the treatment of ischemic heart disease.Methods 76 patients with ischemic heart disease were treated with BMMC transplantation, including 26 patients with acute myocardial infarction (AMI), 26 patients with chronic ischemic heart failure (CIHF), 24 patients with control (10 patients with AMI, 14 patients with CIHF). Bone marrow was extracted from the posterior superior iliac crest, and BMMC was isolated by gradient density method. The cell suspension was adjusted to 2×106/ml, and the BMMC was injected with high pressure under the balloon filling of the infarction-related coronary artery, and the injection was repeated for 6~8 times, or the BMMC was injected with high pressure under the balloon filling of the coronary artery. The clinical and laboratory indexes, two-dimensional echocardiography and positron emission tomography were observed. Results 52 patients were followed up for 2 years. Left ventricular ejection fraction (LVEF) of AMI patients increased by 5.8% (53.9%±2.9%vs 59.7%±1.5%, P<0.05) and 3.8% (57.7%±1.7%, P>0.05) at 1 year after BMMC transplantation, but the difference was not statistically significant. Left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) did not improve significantly. There was a significant difference between BMMC transplantation group and pre-operation (P<0.05). LVEF increased by 8.8% and 9.2% (P<0.01) and LVESV decreased by 20.4% and 27.8% (all P<0.05) in CIHF patients at 1 and 2 years after BMMC transplantation compared with pre-operation, respectively. Conclusion BMMC treatment can significantly improve the cardiac function in patients with CIHF, but has no long-term effect on improving left ventricular systolic function in patients with AMI, only limiting ventricular remodeling.

Objective to investigate the apoptosis of K562 cells induced by highly selective protease inhibitor MG132 and its effects on the activity of transcriptional nuclear factor kappa B (NF-κ B) and the expression of anti-apoptotic protein Survivin (Survivin). Methods the apoptosis of K562 cells was detected by cell morphology and flow cytometry, and the activity of NF-KB and the expression of Survivin were analyzed by immunocytochemistry and Western blot. Results the apoptosis of K562 cells was induced by different concentrations of MG132 for 24 h in a dose-dependent manner. The expression of NF-κ B and Survivin was abnormally high in K562 cells, but it was significantly down-regulated after MG132. After 2, 4, 6 and 8 μ mol/L MG132 was applied to K562 cells for 24 h, the activity of NF-κ B was down-regulated to 75.0%±3.7%, 59.9%±5.3%, 45.4%±5.7% and 25.0%±4.2%, respectively, while the expression of Survivin protein was down-regulated to 90.9%±10.1%, 66.7%±5.2%, 45.4%±5.7% and 30.3%±6.2%, respectively

Objective to investigate the expression of costimulatory molecules CD80, CD86 in HL-60 cells induced by proteasome inhibitor MG132 and its effect on mixed lymphocytes. Methods Flow cytometry was used to detect the expression of costimulatory molecules CD80, CD86 and cell viability in HL-60 cells induced by MG132. Analysis of CD80 and CD86 mRNA expression by reverse transcription polymerase chain reaction (RT-PCR); After 75Gy irradiation of HL-60 cells induced by MG132, the proliferation of HL-60 cells on healthy human mononuclear cells was detected by CCK-8 after increasing the expression of costimulatory molecules. Results MG132 upregulated the expression of CD86 in HL-60 cells, and high concentration of MG132 directly killed HL-60 cells, and MG132 induced the expression of costimulatory molecule CD86 in HL-60 cells, which promoted the proliferation of healthy human mononuclear cells.

Objective to express human hyperpolarization-activated cyclic nucleotide-gated potassium channel subtype 2 (hHCN2) and subtype 4 (hHCN4) genes in HEK293 cell line, and to observe the electrophysiological characteristics of the expressed channels. Methods The cNDA subclones containing the target genes hHCN2 or hHCN4 were cloned into adenovirus shuttle vector pAdTrack-CMV, the shuttle vector and viral backbone vector pAdEasy-1 were recombined in E. coli, the virus was packaged and amplified, and the hyperpolarization-activated potassium currents (If) on HEK293 cells transfected with hHCN2 and hHCN4 were recorded by whole cell patch clamp technique. Results hHCN2 and hHCN4 transfected HEK293 cells produced hyperpolarization-activated inward currents. The half-maximum activation voltages of the two channels were-114.8 mV ± 3.3 mV and-125.9 mV ± 2.9 mV, respectively, and the slopes of reverse curves were 11.1 mV ± 1.2 mV and 13.7 mV ± 1.3 mV, respectively. The activation kinetics of the two channels were obviously different. When the stimulation voltage was-110 mV, the activation time constants of the two channels were 0.99 s ± 0.21 s and 8.47 s ± 2.85 s, respectively. The relative permeability of the two channels to sodium and potassium ions was 0.40 and 0.34, respectively. Both currents could be blocked by 2mmol/L cesium chloride (CsCl). Conclusion The target genes hHCN2 and hHCN4 were successfully expressed on HEK293 cells, and the two channels formed had obviously different activation kinetics.

Objective to evaluate the properties and drug release characteristics of domestic rapamycin-polylactide glycolide (PLGA) peripheral arterial eluting stents. Methods Self-made PLGA and rapamycin were used to prepare rapamycin-PLGA film, and 12 domestic nickel-titanium alloy peripheral vascular stents were coated with this film. The macroscopic morphology of the drug coating on the surface of the stents was observed by OLYMPUS bulk microscope, and the three-dimensional morphology and surface roughness of the coating surface were observed and analyzed by Nanoscope ⅢA atomic force microscope. The hemocompatibility, in vitro degradation behavior and in vitro pharmacokinetics of the eluting stents were studied. The data were measured by standard curve, release curve fitting measurement, and the release curve measurement of LPMS/PLGA coated multi-stents were analyzed. Results The surfaces of the drug films of the 12 stents were smooth, the layer thickness was uniform, and there were no cracking, falling off or warping. The macroscopic morphology of rapamycin-PLGA eluting stents in OLYMPUS bulk, the coated stents were free of entanglement and adhesion, and the coating surface was uniform and smooth. There are mechanical scratch micropits, but after the micropits of the substrate were covered by the PLGA drug-loaded coating, the platelets adhered to the surface of the PLGA coating had some deformation and extended out of the pseudopod, and the platelets were partially activated without aggregation; The number of platelets adhering to the surface of the rapamycin-containing coating was significantly reduced, without deformation and aggregation, and the platelets were in inactivated state.In the in vivo environment simulation system, the degradation rate of PLGA was about 20% within 2 weeks, and the degradation rate was gradually accelerated until completely degraded in 2 to 6 weeks.The results of the in vitro pharmacokinetic experiment of rapamycin-PLGA-eluting stent showed that the drug release of the drug-eluting stent could last for 50 days.The release amount was measured at 0, 1, 3, 5, 7 and 9 days, and the release curve was in accordance with Higuchi equation:Mt/M∞ (%) =3.1722*t1/2 (h) -5.682 (γ =0.9944, n =5). The measured curve fit well with the fitting curve, γ =0.9944. At 30 days, there was still a relatively stable drug release. The 24 h burst release amount was 11.02%; 9 d The cumulative release amount was 41.23%; Conclusion the coating of the domestic rapamycin-PLGA peripheral artery-eluting stent is uniform and smooth, which can effectively control the drug release, and has further clinical application value.

Prostate cancer is one of the most common male malignant tumors. Although the incidence rate in China is far lower than that in the West, with the continuous improvement of living standard and diagnosis technology, the incidence of prostate cancer is on the rise [1].

The latest data published in the European Journal of Cardiology provide a new scheme for the prevention of cardiovascular events in hypertensive patients. On December 11th, it was learned from the press conference "Simultaneous Interpretation of the Latest Results of the Largest Hypertension Study in Europe" organized by the Cardiovascular Physicians Branch of Chinese Medical Physicians Association that the combined use of the calcium antagonist Norvasil (amlodipine besylate) and the statin Lipitor (atorvastatin) in hypertensive patients with cardiovascular risk factors (smoking, diabetes, dyslipidemia, men aged ≥55 years and women aged ≥65 years) reduced the relative risk of fatal coronary heart disease and non-fatal myocardial infarction by 53% compared with Norvasil alone. These new data from the ASCOT study (Anglo-Scandinavian Cardiac Endpoint Study) were published in the December 11th, 2006 issue of the European Journal of Cardiology.

With the popularization of digestive endoscopy and the improvement of endoscopic diagnosis and treatment technology, the requirements for the accuracy and timeliness of disease diagnosis are also increasing constantly. Therefore, the pigment endoscopy (chromoendoscopy) technology came into being in Japan at the end of last century, and it was gradually popularized in some large hospitals.

At present, methimazole is the first choice for the treatment of Graves' disease (GD). agranulocytosis (agranulocytosis) is a rare but serious side effect in the treatment of antithyroid drugs (ATD) [1]. Cases of agranulocytosis caused by domestic methimazole (tapazole) have been reported from time to time, but there have been no reports of agranulocytosis caused by methimazole (trade name: saizhi). A patient with severe agranulocytosis caused by saizhi was found in our hospital, which is sorted out as follows.