Volume 87  ·   Issue 04  ·  2007

With the rapid development of molecular biology research, especially the development of genomics, proteomics and related technologies, there is an urgent need for some means to monitor the process of its research object in living organisms. Therefore, molecular imaging (molecular imaging), which takes cells, genes or molecules and their transmission pathways as imaging objects, has emerged as the times require. After a hundred years, medical imaging has finally developed from traditional medical imaging based on anatomical structure to molecular imaging based on cell/molecule structure and function, which represents the future of medical imaging and will have an important influence on modern and future medical models.

Objective to prepare a gadolinium-containing nanomaterial for magnetic resonance molecular imaging. Methods Tetramethoxysilane was used as the source of silicon oxide nanomaterial and gadolinium ions were doped into tetramethoxysilane silicon material to prepare gadolinium-containing nanomaterial. The nanometer size of the material was observed by electron microscope; The magnetic sensitivity of the material was examined by MRI in vitro, and the magnetic sensitivity of the material was examined by Gd-DTPA as a control; The material was injected intravenously, and the distribution characteristics of the material in Balb/c nude mice and CNE-2 nude mice were observed by MRI scanning. Results the prepared gadolinium-containing nanomaterials were short rod-shaped with nanometer size of about 30 to 40 nm. The relaxation rate of the nanometer T1 was significantly higher than that of the conventional contrast agent Gd-DTPA; After intravenous injection in nude mice, MRI scan showed that the signal intensity of T1WI in liver and kidney increased from 226 ± 10 and 283 ± 7 to 352 ± 12 and 328 ± 10, respectively, indicating that the material was mainly distributed in liver; CNE2 transplanted tumors of nasopharyngeal carcinoma in nude mice were significantly enhanced, and the T1WI signal intensity of transplanted tumors increased from 195±5 before injection of contrast medium to 245±7. Conclusion The new gadolinium-containing nanomaterials have high magnetic sensitivity and are expected to be a new carrier for nuclear magnetic resonance molecular imaging.

Objective to observe the effects of different concentrations of ultra-small and ultra-paramagnetic iron nanoparticles (USPIO) on different numbers of rat C6 glioma cells labeled in vitro and with carrier. Methods 1×106, 2×106 and 1×107 rat C6 glioma cells were labeled with USPIO at concentrations of 0, 25 and 50 μ g/ml, and the signal intensity was measured by T1WI, T2WI and GRE/30° sequence scanning with carrier MRI. Results Different numbers of rat C6 glioma cells were cultured with USPIO at concentrations of 0, 25 and 50 μ g/ml for 12 h, and the same number of cells labeled with USPIO at different concentrations were measured with different sequences by in vitro MRI. The differences between the groups measured by GRE/30° and T2WI were statistically significant, 50 and 25 μ g/ml groups The signal intensity of rat C6 glioma cells labeled with USPIO at the same concentration was related to the number of cells (t =5.16, 2.35, 4.41; P<0.05). The staining degree of the labeled cells was gradually deepened from 25 to 50 μ g/ml under Prussian blue staining microscope. The extent of the lesion and signal intensity of rat C6 glioma cells labeled with USPIO at the carrier concentration of 25 μ g/ml were clearly shown in MRI imaging. Conclusion USPIO can label rat C6 glioma cells. The signal intensity of MRI is inversely proportional to the number of cells labeled with USPIO at the same concentration.

Objective to observe whether mouse bone marrow mesenchymal stem cells (MSCs) differentiated into cells with hepatocyte phenotype and function in the specific microenvironment of the liver, and to explore the feasibility of treating liver function damage.Methods 20 nude mice were randomly divided into 4 groups, 5 in each group: Group A: CCl4 mixed with olive oil 1:1, injected intraperitoneally at 1 ml/kg, twice a week.After 1 week, 1×106GFP positive MSCs were transplanted through the tail vein, and CCl4 was injected twice a week; Group B: CCl4 was injected with the same amount of normal saline via tail vein as in group A; Group C: normal mice, cell transplantation was the same as group A; Group D: normal control. All the animals were sacrificed 4 weeks after operation, and the liver function was detected in serum. HE and Masson staining were performed for histological observation, and double fluorescence staining was performed to confirm GFP-positive cells and to observe whether they expressed hepatocyte-specific proteins. Results the liver fibrous tissue proliferation of recipients in Group A and B showed that the liver function injury model was successfully made, and the difference in the percentage of collagen distribution between the two groups was not statistically significant (10.5±1.5 vs 12.7±1.6, t = -2.238, P>0.05). The level of albumin in group A was significantly higher than that in group B (24.4g/L±3.3g/L vs 18.6g/L±2.9g/L, P<0.05). The difference of serum alanine aminotransferase (ALT) levels between the two groups was statistically significant (121 U/L±21 U/L vs 192 U/L±29 U/L, P<0.05). Conclusion MSC transplantation can effectively induce the migration and proliferation of MSC to the liver under the microenvironment of persistent hepatocyte damage, suggesting that MSC transplantation can repair the damaged liver function to some extent.

A 37-year-old woman underwent myomectomy 7 years ago and subtotal hysterectomy 4 years ago for recurrence of uterine fibroids. Recently, she felt lower abdominal pain, and B-ultrasound examination showed mixed pelvic masses. MRI pelvic examination showed that multiple nodular masses of different sizes were found in the pelvic cavity, the largest one was located above the bladder, about 6 cm ×7 cm, with clear edges, and the T1WI signal was low, and there were small nodular high signals with clear edges between the masses (Figure 1A ~ E). Chest X-ray examination: See Figure 2.

Objective to explore the method of lymph node tracing in advanced gastric carcinoma (AGC). Methods During radical resection of gastric angle AGC with group 3 lymph node (No.3) metastasis, dye was injected into or around the node of No.3 metastasis, and the secondary anterior lymph node (SSLN) near the metastasis nodule was biopsied. Routine HE staining and immunohistochemical examination were performed. Results SSLN was found in 38 of 46 cases with 82.6% (38/46). SSLN metastasis was found in 30 cases with 78.9% (30/38) of pathological examination and immunohistochemical examination, and the positive rate of SSLN was 76.4% (52/68). The distribution of SSLN was as follows: the number of SSLN in groups 7, 5, 4, 6, 9 and 8 was 40, 9, 7, 5, 4 and 3 respectively. The number and positive rate of SSLN were 31 (77.5%), 9 (100%), 5 (71.4%), 4 (80.0%), 2 (50.0%) and 1 (33.3%) respectively SSLN tracer technique provides an important reference for guiding rational scientific and individualized lymph node dissection of AGC.

Objective to evaluate the short-term and long-term efficacy of small vessel stent point placement and rapamycin-eluting stent in the treatment of small vessel long lesions.Methods Patients with small vessel and long lesions (vessel diameter<3.0mm, lesion length>20mm) who underwent percutaneous coronary intervention from December 2002 to August 2005 were divided into small vessel stent point placement group (SVS group) and rapamycin-eluting stent group (SES group) according to their treatment strategies.The incidence of in-stent restenosis, target lesion revascularization (TLR) and major adverse cardiac events (MACE) at 6 months after surgery in the two groups.Results A total of 206 patients were enrolled, including 113 in SVS group and 93 in SES group.There was no significant difference in basic clinical and vascular characteristics between the two groups.In SES group, 2 patients had tortuous and calcified vessels, and CYPHER stent could not pass through, and the operation was successfully completed after switching to DRIVER stent.During the follow-up period, the incidence of in-stent restenosis in SES group (4.0% vs 26.5%, P<0.05) and TLR (2.2% vs 10.6%, P SVS dot placement is optional.

Objective to further understand the clinical characteristics of hyperthyroid heart disease (hyperthyroid heart disease) Methods the clinical data of hyperthyroid heart patients were retrospectively analyzed, including 75 cases, 30 males and 45 females, aged 17-84 years, with a course of 1 month-30 years; 47 cases (63%) with heart failure, 47 cases (63%) with atrial fibrillation, 2 cases (3%) with sick sinus syndrome; There were 48 cases of left atrial enlargement (66%), 31 cases of left ventricular enlargement (43%), 30 cases of right atrial enlargement (41%), 35 cases of right ventricular enlargement (47%), 18 cases of whole heart enlargement (25%), 48 cases of mitral valve regurgitation, 45 cases of tricuspid valve regurgitation, 34 cases of aortic valve regurgitation, and 33 cases of pulmonary hypertension (44 mm Hg ± 7 mm Hg, left ventricular ejection fraction 60% ± 19%). The key to treatment is hyperthyroidism.

Objective to study the relationship between different clinical manifestations of human cytomegalovirus (HCMV) infection and cytomegalovirus glycoprotein B (gB) genotype in infants. Methods In 107 infants with HCMV infection with clinical symptoms and 25 infants without clinical symptoms, the gB gene fragment was amplified by nested PCR, and the gB gene was typed by restriction fragment length polymorphism analysis (RFLP), and some samples were verified by sequencing. Results Among the 107 infants with clinical symptoms, 53 cases of gB Ⅰ, 20 cases of gB Ⅱ, 18 cases of gB Ⅲ, 7 cases of gB Ⅰ and Ⅱ mixed, 5 cases of gB Ⅰ and Ⅲ mixed, 4 cases of gB Ⅱ and Ⅲ mixed, and no gB Ⅳ was found. Among the 53 infants with hepatic impairment, 36 cases of gB Ⅰ, 5 cases of gB Ⅱ, 7 cases of gB Ⅲ, 3 cases of gB Ⅰ and Ⅱ mixed, 2 cases of gB Ⅰ and Ⅲ mixed, and the majority of gB Ⅰ were found (P<0.05). The similarity is 97.06% ~99.64%. Conclusion RFLP is a clear and reliable genotype for HCMV. In infants infected with HCMV with hepatic impairment, gB Ⅰ is the dominant genotype.

Objective to investigate the effects of methylcobalamin and folic acid therapy on the activity of plasma homocysteine (Hcy) and homocysteine thiolactonolytic enzyme (HTase/PON) in type 2 diabetic patients. Methods 120 patients with type 2 diabetes mellitus were divided into 4 groups, 30 cases in each group, group Ⅰ: no intervention control group; Group Ⅱ: Folic acid was given 5 mg orally, once a day; Group III: Methylcobalamin 500 μ g intramuscular injection, once a day; Group IV: Folic acid 5 mg + methylcobalamin 500 μ g intramuscular injection, once a day; Results the plasma Hcy levels in the intervention group were significantly lower than those before treatment (P<0.05), and the decreases were 37.3% in group IV, 21.7% in group III, 14.0% in group II and 2.8% in group I (F =28.894; P =0.000). The activity of serum HTase/PON was significantly increased (all P<0.05), which were 17.6% in group IV, 8.0% in group II, 3.4% in group III and 2.7% in group I, respectively (F =36.100, P =0.000). Conclusion Methylcobalamin has a significant effect on reducing plasma Hcy; Folic acid may indirectly affect the activity of Hcy and HTase/PON through its antioxidant properties.

Objective to analyze the distribution characteristics of liver enzymes in patients with non-alcoholic fatty liver disease (NAFLD), and the relationship between liver enzymes and metabolic syndrome (MS). Methods 318 patients with NAFLD without diabetic history were collected. The medical history was asked, the height, weight, waist and hip circumference, blood pressure were measured, alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), blood lipid, fasting and 2 h after glucose tolerance test, blood glucose, insulin and hepatitis virus markers were measured. Results The prevalence of MS (ATPⅢ) in this population was 38.7%; There were 174 cases (54.7%) with abnormal liver enzymes, among which 123 cases with MS had abnormal liver enzymes (48.8%). The liver enzymes in MS group were higher than those in non-MS group. With the increase of the number of MS components, the proportion of abnormal liver enzymes increased, and the risk of abnormal ALT, AST and GGT increased [OR values (95% CI) were 1.78 (1.37~2.32), 1.65 (1.19~2.29), 1.81 (1.35~2.43), respectively]. Conclusion More than 50% of NAFLD patients had abnormal liver enzymes, and the detection rate of MS in patients with abnormal liver enzymes increased significantly; Coexistence of multiple MS components may be a risk factor for elevated liver enzymes in NAFLD.

Objective to investigate the molecular mechanism of the pathogenesis of hereditary hemorrhagic telangiectasia.Methods (1) The mutant exons and their adjacent splicing sites were found by PCR-SSCP. (2) The type of mutation was determined by DNA sequencing.( 3) The splicing pattern was determined by reverse transcription-polymerase chain reaction (RT-PCR). Results The mutant sites in exon 4 and some adjacent introns of the amplified ALK1 gene were found by PCR-SSCP. The mutant fragment was detected by DNA sequencing, and the mutation of the adjacent base A>T (Ⅳ S4+3A>T) at the donor splicing point of exon 4 was found, which was confirmed by reverse sequencing. The mRNA expression of ALK1 gene was detected by RT-PCR, and the loss of exon 4 was found by electrophoresis and sequencing. Conclusion The mutation of Ⅳ S4+3A>T in ALK1 gene caused the abnormal expression of ALK1 gene, and the non-functional truncated protein was formed, which caused HHT2.

Objective to confirm the pathogenesis and inheritance of X-linked lymphocytic dysplasia (XLP) in China.Methods The clinical subjects were 14 members of three generations of the proband's parental family; Retrospectively analyze the hospitalization history of the patients with the disease; The growth and development history and past history of the disease-free patients were asked on the spot, physical examination was performed, and cards were established for tracking. The genetic research objects were 4 siblings of the proband, sister, younger brother and both parents. The genomic DNA of mononuclear lymphocytes was extracted, and the fragment of SH2D1A gene was obtained by PCR amplification. The mutated exon fragment was obtained by single strand conformational polymorphism analysis (SSCP), and the mutation was detected after purification and sequencing. Results The proband and his brother developed lethal infectious mononucleosis (IM) with virus-associated hemophagocytic syndrome (VAHS), and all died about 40 days after the course of the disease. The genetic analysis results showed that the C base of the 462 nucleotide of the proband's SH2D1A gene cDNA mutated to T base, forming the stop code TGA, and then the proband's brother was clinically diagnosed with Langerhans cell histiocytosis (LCH). The proband's mother is heterozygous for C-base and T-base in the same part of SH2D1A gene.No mutation of SH2D1A gene was found in the proband's father and sister, and they and other members of their family had no similar medical histories.Conclusion (1) The proband and his sibling can be clinically diagnosed as XLP patients.2) The proband's younger brother can be definitively diagnosed as XLP patient.LCH may also be a new clinical phenotype of XLP. (3) The proband's mother is a carrier of mutant gene.The pathogenesis of XLP in this family conforms to the X-linked recessive inheritance law. (4) The method of detection and analysis of SH2D1A gene established in this study can be applied to the diagnosis, treatment and research of XLP in China.

Objective to study the long-term effects of recurrent convulsions on the expression of γ-aminobutyric acid (GABA) A receptor (GABAAR) α 1 and β 2 subunits in the brain of neonatal rats and the long-term changes of memory function and convulsion threshold in adulthood. Methods SD rats at 7 days after birth were randomly divided into two groups, 16 rats in each group. The convulsions in the convulsion group were induced by inhalation of trifluoroethyl ether once a day, each time lasting 30 min for 6 days; Morris water maze experiment was carried out between 61 and 65 days after birth, and the threshold of convulsion was measured by intraperitoneal injection of pentylenetetrazole at 75 days after birth. Immunohistochemistry and reverse transcription PCR were used to observe the expression changes of GABAAR α 1 and β 2 subunits in cerebral cortex and hippocampus of rats. Results The plateau-finding time (82 424 ms ± 35 622 ms) was significantly longer than that in the control group (40 712 ms ± 29 467 ms, P =0.001) at 64 days after birth. At 65 days after birth, the number of target crossings (1.2 ± 0.9 times) in the convulsion group was significantly less than that in the control group (3.1 ± 1.3 times, P<0.01). The incubation period of convulsion after PTZ injection in the convulsion group (1487 s ± 662 s) was not significantly different from that in the control group (1841 g ± 648 s) (P =0.133). The immunochemical cumulative absorbance of GABAAR α 1 subunit in the parietal lobe and hippocampal CA1, CA2 and CA4 regions in the convulsion group was significantly lower than that in the control group The immunochemical accumulated optical density of GABAAR β 2 subunit in the thalamus and hippocampal CA1~4 regions of convulsive rats was significantly lower than that in the control group (all P<0.05), and the expression of α 1 and β 2 subunit mRNA in the hippocampus of convulsive rats was significantly lower than that in the control group (all P<0.05). Conclusion Recurrent convulsions in neonatal rats can cause long-term changes in the expression of GABAAR α 1 and β 2 subunits in the brain, which may be related to the adult memory impairment caused by recurrent convulsions in neonatal period.

Objective to investigate the protective effect of bone marrow mesenchymal stem cells (MSC) on hypoxia-induced cardiomyocyte apoptosis and its possible mechanism.Methods MSC and neonatal rat cardiomyocytes were isolated and cultured. After the cultured neonatal rat cardiomyocytes were treated with hypoxia, MSC or its conditioned culture medium were added and co-cultured under anoxia (95%N2+5%CO2, persistent hypoxia group) or normal oxygen (hypoxia/reoxygenation group) for 72 h, and the percentage of apoptotic cells was calculated by Hoechst nuclear staining; The changes of apoptosis-related proteins Bcl-2 and Bax were detected by Western blot. Results Apoptosis of cardiomyocytes was induced by persistent hypoxia, and the apoptosis rate was 51.6%±2.4%. The apoptosis rate of cardiomyocytes was significantly reduced by co-culture with MSC or its conditioned medium, which was 15.1%±5.4% and 24.0%±4.2%, respectively (both P<0.01); Hypoxia/reoxygenation injury could induce apoptosis of cardiomyocytes, the apoptosis rate was 20.9%±2.7%, and the apoptosis rate was significantly reduced when cardiomyocytes were co-cultured with MSC (11.5%±3.7%, P<0.05); The apoptosis rate of cardiomyocytes was slightly decreased (20.1%±4.2%,P>0.05) when co-cultured with MSC conditioned medium. The expression of Bax was higher in myocardium during apoptosis, but when co-cultured with MSC or its conditioned medium, the expression of Bax was decreased to varying degrees, which was consistent with the decrease of apoptosis rate of cardiomyocytes, but Bcl-2 did not change obviously. Conclusion MSC has a protective effect on apoptosis induced by hypoxia in vitro, and its mechanism may be that the expression of some proteins of Bcl-2 family in cardiomyocytes was affected by direct contact between cells and paracrine cytokines.

The patient was a 38-year-old farmer who was admitted to Huashan Hospital of Fudan University on June 24, 2005 due to the discovery of proteinuria for 2 years. In 2003, the patient went to a local hospital for gynecological diseases, and the urine protein (+) was checked, but no attention was paid to it. In early 2004, the patient went to another hospital for urine protein (+ + +) because of fatigue, and the renal function was normal. She was transferred to her hometown hospital for treatment, and was treated with levofloxacin and astragalus, and was transferred to the hospital after slightly better. In March 2005, the urine protein was checked for 24 hours in Huashan Hospital of Fudan University. There were no symptoms such as fever, rash, photosensitivity and joint pain during the course of the disease. There was no history of hypertension, diabetes, viral hepatitis, etc., and no family history of renal disease.

Breast cancer is a disease with high incidence in women. The incidence rate is 25.7/100,000 in Beijing and 27.2/100,000 in Shanghai [1], and it is increasing in recent years. Up to now, surgical resection is still one of the main methods of breast cancer treatment.

In September 2006, the official journal of the European Society for the Study of Diabetes (EASD) published a review by its editor-in-chief, Edwin Gale, entitled "Declassifying Diabetes. Diabetology, 2006, 49: 1989-1995".

The patient was a 31-year-old male, married and childbearing. He went to the doctor for hematospermia and frequent urination for 1 month. The outpatient B-ultrasound found that the right seminal vesicle was substantially occupying space and was admitted to the hospital. Digital rectal examination showed that the right posterior and upper prostate was about 2 cm in diameter, and the round texture was tough, with a smooth surface, clear boundary and no tenderness.

A 55-year-old farmer was admitted to the emergency department due to exertion palpitations and shortness of breath for 1 month, aggravated for 2 days. Physical examination showed chronic disease, poor nutritional status, slight cyanosis of lips, full jugular vein, center trachea, clear breathing sounds in both lungs, small heart boundary, heart rate 102 beats/min, uniform rhythm, grade III/6 systolic murmur can be heard at the left margin of sternum, no abnormality in abdomen, and mild edema in both lower limbs.

In the process of human immunodeficiency virus (HIV) infection, the immune system plays an important role in controlling the replication of the virus, and it is also an important factor in protecting the special populations related to HIV infection, such as those who have not been exposed to HIV and those who have not progressed for a long time. Over the years, the research on the immune response of HIV infection has clarified the law of the interaction between HIV and immune system to a certain extent, and provided the basis and idea for the treatment of AIDS and the research and development of vaccine.

The refractory retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP) cause blindness mainly due to the damage and loss of retinal photoreceptors (i.e. photoreceptor cells).

It is critical to ensure the correct distribution of homologous chromosomes to daughter cells during cell division. Until now, it has been assumed that the average distribution of homologous chromosomes in cells is only controlled by centromeric checkpoint kinases. When microtubules are correctly connected to centromeres, these kinases inform cells that the precise distribution of homologous chromosomes can be carried out. Scholars from the Max Planck Institute of Molecular Genetics in Berlin have conducted in-depth research on this control mechanism, and the results are published in<Science, 2006, 314:654-657.