Volume 85  ·   Issue 43  ·  2005

Breast cancer is a common malignant tumor in women, and its incidence rate is the first among female malignant tumors in Europe and America. Although China belongs to a relatively low incidence area of breast cancer, its incidence rate is increasing year by year, and has risen to the first place among female malignant tumors in some big cities. Although the incidence rate of breast cancer is still rising, the mortality rate has begun to decline. On the one hand, more early cases are found, and on the other hand, it benefits from the progress of treatment methods. The treatment methods of breast cancer include surgery, radiotherapy, chemotherapy, endocrine therapy and biological therapy. The new concept of breast cancer treatment is the combination of science and humanities, and the treatment trend includes minimally invasive surgery, stereoscopic radiotherapy and targeted drug therapy. 　　

Due to work reasons, the author has the opportunity to participate in the writing, revision and review of many papers, and deeply feels that there are defects in the overall design framework of some papers. The common problem is that the articles are written very large and involve a wide area, but they are all written in a "dragonfling" way with shallow content. After reading, I don't know what problem the author wants to explain, nor where the author's conclusion comes from, and the quality of the papers is not high. Therefore, the author proposes that the principle of "one paper explains one problem clearly" should be followed in the writing and review of papers. The following is a brief exposition of this principle by the author, and I hope that experts from all aspects will participate in the discussion. 　　

Objective to investigate the inhibition of HBV surface antigen (HBsAg) and e antigen (HBeAg) in HepG2.2.15 (2.2.15) cells by RNA interfering (RNAi) vector pGE-HBVP, in order to clarify the effect of small interfering RNA (siRNA) in HBV P region on HBV replication and protein expression. Methods pGE-HBVP was constructed and identified, and transfected into intact HBV replication model 2.2.15 cells. The contents of HBsAg and HBeAg were detected and analyzed by chemiluminescence immunoassay, and the expression of HBsAg was observed by immunocytochemistry. Results Five RNAi expression vectors pGE-HBVP1~ pGE-HBVP5 targeting HBV P region were successfully constructed, among which pGE-HBVP1 and pGE-HBVP2 significantly inhibited the secretion and expression of HBsAg and HBeAg The positive rate of HBsAg expression in 2.2.15 cells transfected with pGE-1 empty vector was about 82%, while the positive rate of HBsAg expression in 2.2.15 cells transfected with pGE-HBVP2 was about 50%, which was significantly lower than that of pGE-1 empty vector. Conclusion RNAi targeting the P region of HBV can inhibit the secretion and expression of HBV virus antigen.

Objective to investigate the relationship between adipose tissue phosphoallyl alcohol carboxykinase (PEPCK) and insulin resistance in high-fat feeding rats and the effect of rosiglitazone on it. Methods 8-week-old male SD rats were divided into two groups: short-term group (33 rats at 8 weeks) and long-term group (30 rats at 28 weeks). Each group included normal feeding group (11 rats, 10 rats), high-fat group (11 rats, 10 rats) and rosiglitazone group (11 rats, 10 rats). Fasting blood was taken to measure blood free fatty acid (FFA) and triglyceride at the end point of the experiment. The insulin sensitivity of each group was measured by normal blood glucose high insulin clamp method and tissue uptake capacity of 3H-2-deoxyglucose (2-DG). The changes of adipose PEPCK mRNA expression were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Results Compared with the normal group, long-term high-fat feeding increased triglyceride by 32% (P<The glucose infusion rate (GIR) decreased by 51% in the short-term high-fat feeding group (P<0.01); The uptake rate of 2-DG in liver, muscle and adipose tissue decreased by 42%, 36% and 48% respectively in the long-term high-fat feeding group (P<The content of PEPCK mRNA in adipose tissue of the short-term and long-term high-fat feeding groups did not change. Compared with the high-fat group, the FFA of the short-term and long-term groups was 125% and 49% lower respectively (P<0.05); Triglycerides decreased by 54.0% and 23%, respectively (P<0.01); GIR increased by 150% in the short-term intervention group (P<0.01); In the long-term intervention group, the uptake rates of 2-DG in liver, muscle and adipose tissue were 39%, 66% and 66% higher, respectively (all P<0.01); At the same time, short-term and long-term rosiglitazone intervention increased PEPCK mRNA content in adipose tissue of rats by 165% and 43%, respectively (P<Conclusion Thiazolidinediones may be related to the improvement of insulin sensitivity by inducing PEPCK expression in adipose tissue, increasing fatty acid re-esterification and reducing circulating FFA.

Objective to analyze the effect of smoking on peripheral arterial disease (PAD) of lower limbs. Methods the ankle-brachial index of 3379 male patients (aged 40-98 years) in 28 hospitals in Beijing and Shanghai were measured. The ankle-brachial index ≤0.9 was diagnosed as PAD. The patients were divided into smoking group (2253 cases) and non-smoking group (1126 cases). The data were collected and statistically processed by questionnaire. Results the ankle-brachial index of smoking group (1.00±0.24) was significantly lower than that of non-smoking group (1.03±0.22, P<0.05). There were 2253 cases in smoking group, 562 cases with PAD, the prevalence rate was 24.94%, 1126 cases in non-smoking group, 232 cases with PAD, the prevalence rate was 20.60%, and the age-adjusted relative risk (ORMH) was 1.480 (95% CI: 1.237-1.770). There was a dose-response relationship between smoking grade and risk of PAD. Conclusion Smoking is an important risk factor for PAD, and the risk of PAD increases with the increase of smoking amount.

Objective to evaluate the efficacy and safety of hydrochloric acid/glucosamine sulfate in the treatment of knee osteoarthritis.Methods A total of 142 patients with knee osteoarthritis were randomly divided into 2 groups by a multicenter, randomized, positive drug parallel controlled clinical study. 71 cases in the experimental group and 71 cases in the control group were given glucosamine hydrochloride 480 mg/time and glucosamine sulfate 500 mg/time, respectively, oral medication 3 times a day for 4 weeks.The Lequesne index was used as the efficacy score criterion to observe the changes of knee joint symptoms before and after taking the medication, including resting pain, movement pain, tenderness, swelling, morning stiffness and the improvement degree of walking ability, and the adverse reactions and laboratory biochemical indexes were recorded. Results After 4 weeks of treatment, the total Lequesne index scores of the experimental group and the control group decreased to 3.4 ± 1.9 compared with the basic value, respectively (P<0.05) and 3.4±1.8 (P<0.05), the symptom improvement rate was 91.4% (64/70) and 90.0% (63/70), respectively, and the difference between the two groups was not statistically significant (P>0.05); Two weeks after stopping the drug, the original treatment effect was maintained in both groups, and the symptom improvement rate was 92.4% (61/66) and 91.2% (62/68), respectively, and the difference between the groups was not statistically significant (P>0.05); The incidence of adverse reactions was 4.2% (3/71) and 7.0% (5/71) in the experimental group and the control group, respectively. The main manifestations were mild to moderate stomach discomfort and constipation. Conclusion The efficacy and safety of glucosamine hydrochloride in the treatment of osteoarthritis is similar to that of glucosamine sulfate, and it is a safe and effective drug for the treatment of osteoarthritis.

Objective to evaluate the diagnostic and therapeutic significance of liver biopsy in patients with liver function impairment after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Methods 10 patients with Allo-HSCT and liver biopsy were selected from February 1999 to January 2004 in the Institute of Hematology of Peking University People's Hospital. There were 5 males and 5 females aged 15-56 years (median 34.5 years). Among them, 8 cases were leukemia, 1 case was myelodysplastic syndrome and 1 case was severe aplastic anemia. The transplantation methods included unrelated bone marrow transplantation in 1 case, all-consistent Allo-HSCT in 6 cases, haploid transplantation in 1 case and umbilical cord blood transplantation in 2 cases. The pretreatment regimen was whole body irradiation plus cyclophosphamide in 2 cases and non-whole body irradiation regimen in 8 cases. All graft versus host diseases were treated with cyclotin A plus short-course methotrexate plus mycophenolate mofetil regimen. Hematoxylin-eosin and Masson staining were used to observe liver tissues under light microscope and immunohistochemistry. Results 10 patients had liver function damage after Allo-HSCT in 2~5 months, with a median of 3.8 months. HBV and HCV were positive in 7 patients before transplantation, but still positive after transplantation. HBV and HCV were negative in 3 patients before and after transplantation, and the clinical diagnosis was graft versus host disease (GVHD) liver damage. 10 patients had liver function damage, 9 patients had other manifestations of chronic GVHD (cGVHD) with different degrees. All 10 patients had poor liver function improvement after initial treatment according to clinical diagnosis. Liver biopsy was performed 4~12 months after Allo-HSCT (median of 5.5 months). The pathological results showed that 3 patients with hepatitis virus negative liver damage were cGVHD liver damage, and 7 patients with hepatitis virus infection combined with cGVHD liver damage The remaining 7 patients were treated with antiviral and modified immunosuppressive agents. Results 2 patients had liver function recovered and survived. 5 patients died. Among them, 2 patients had poor liver function improvement and died due to pulmonary infection, and 3 patients died due to liver failure and hepatic coma. Conclusion After Allo-HSCT, liver biopsy can play a differential diagnosis and guide further treatment for patients with clinical diagnosis of GVHD liver damage. The prognosis of patients with hepatitis virus infection and GVHD liver damage is poor.

Objective to prepare monoclonal antibodies against soluble antigen of adult Angiostrongylus cantonensis for the detection of circulating antigen (CAg) of Angiostrongylus cantonensis. Methods BALB/c mice were immunized with soluble antigen of adult Angiostrongylus cantonensis. The spleen cells of mice were fused with myeloma cells (SP2/0), and the obtained cell clones were screened and identified by enzyme-linked immunosorbent assay (ELISA) and immunoblotting assay. CAg in serum of experimentally infected rats, mice and patients with Angiostrongylus cantonensis was detected by double antibody (monoclonal antibodies 3F1 and 4H2) sandwich ELISA. Results Three monoclonal antibodies were identified as IgG1 (3F1, 4H2) and IgM (2A2). The supernatant titers of hybridoma cells were 1: 25 600, 1: 25 600 and 1: 12 800, respectively. The ELISA titers of induced ascites were 1: 80 000, 1: 80 000 and 1: 40 000, respectively. All three monoclonal antibodies recognized the protein with relative molecular weight of about 15 000 in adult Angiostrongylus cantonensis. The detection rates of CAg in serum were 84.2% (48/57) and 87.2% (41/47) in rats and mice infected with Angiostrongylus cantonensis, respectively. The detection rates of CAg in serum of patients with Angiostrongylus cantonensis were 86.4% (19/22), and there was no cross-reaction with those of patients with Schistosoma japonicum, Cysticercosis, paragonimiasis and Trichinella spiralis. The CAg in serum of mice was positive at the second week, and the A450 value reached the peak at the fourth week. Conclusion A high sensitivity and strong specificity sandwich ELISA for 3F1 and 4H2 double antibody was established

Objective to evaluate the long-term trend of liver cancer incidence in Qidong, Jiangsu Province for 30 years. Methods The crude incidence rate, world population adjustment rate (WASR), cutoff adjustment rate of 35-64 years, cumulative incidence rate of 0-74 years, percentage of change (PC) and annual percentage of change (APC) of liver cancer were calculated using the data of Qidong tumor registry reports from 1973 to 2002, and the comparative analysis of incidence rate of period, age and cohort was performed. Results The 30-year average crude incidence rate of liver cancer in Qidong was 59.28/100,000, of which 91.65/100,000 for males and 27.64/100,000 for females, and the sex ratio of male to female incidence was 3.32:1. WASR was 58.71/100,000, of which 93.32/100,000 for males and 26.46/100,000 for females. The cutoff adjustment rate of liver cancer in 35-64 years was 143.61/100,000, and the cumulative incidence rate in 0-74 years was 6.07%. The crude incidence rate was +30.90% for PC and +1.58% for APC. The adjusted rate of PC was +12.33% and APC was +0.41%. The data showed that the overall incidence of liver cancer increased in the latter 15 years, but the incidence of the age group under 35 years decreased significantly. The period trend analysis also showed that the incidence of all age groups under 35 years old had decreased; The birth cohort analysis showed that the incidence rate of birth cohort decreased after 1963. Conclusion The 30-year crude incidence rate of liver cancer in Qidong high incidence site showed an overall upward trend, which may be related to the increase of middle-aged and elderly population; However, many years of prevention and treatment work in the field have had an impact on the incidence of liver cancer in young people, and there is a downward trend.

Objective to investigate the cytotoxic effects of cytotoxic T cells (CTL) and natural killer cells (NK cells) on autoplatelets and their mechanisms. Methods (1) The expression of CD95 ligand (FasL), tumor necrosis factor (TNF α) and tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) on CD8+ cells in patients with idiopathic thrombocytopenic purpura (ITP) and normal controls was detected by flow cytometry. (3) The expression of granzyme B and perforin mRNA in CD8+ cells in patients with ITP and normal controls was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results (1) After platelet incubation alone, the positive rate of annexin V marker was higher than that in patients with ITP and normal controls (3.2% ± 1.1% (2) The positive rate of annexin V marker in platelets of ITP patients (7.6%±2.8%) was significantly higher than that of normal controls (3.6%±0.9%, P<0.01); (3) After platelet incubation with NK cells, the positive rate of annexin V marker in platelet of ITP patients (3.5%±1.1%) was not significantly different from that of normal control group (3.6%±1.0%) (P>0.05); (4) The expressions of FasL and TNF α on the membrane surface of CD8+ cells in ITP patients (17.5%±4.4%, 11.9%±4.9%) were higher than those in normal controls (8.9%±1.5%, 6.4%±2.1%, all P<0.05); There was no significant difference in the expression of TRAIL on the membrane surface of CD8+ cells in ITP patients (16%±4%) and the normal control group (14%±3%) (P>0.05); (5) The expressions of granzyme B and perforin mRNA in CD8+ cells in ITP patients were higher than those in normal controls (1.63%±0.22%, 1.80%±0.31%, all P<Conclusion CTL is involved in the killing effect of self-platelet in patients with ITP; NK cells have no obvious killing effect on their own platelets. Apoptosis mechanism and cytoplasmic granule-dependent mechanism are the specific pathways of CTL killing platelets.

Objective to identify the structural characteristics of plasmid-mediated AmpC gene and its surrounding sequences in multidrug-resistant Klebsiella pneumoniae, and to clarify the mechanism of plasmid-mediated AmpC enzyme propagation. Methods Plasmids of Zygobacteria were extracted and digested with restriction endonuclease HindIII. The sticky ends of DNA fragments were filled with Taq enzyme and single deoxyadenosine (A) was added at the ends, and T-A cloned with pGEM-T Easy vector. The recombinant bacteria were screened on plates containing ampicillin and cefoxitin, extracted and analyzed by enzyme digestion, and the cloned fragments were sequenced by step-shift method. The recombinant bacteria were subjected to drug susceptibility test and isoelectric point analysis. Results the recombinant plasmid pT948 containing 5.2 kb insert was cloned and screened. The insert sequence was found to contain an ampC (blaDHA-1) gene and an ampR regulatory gene. An insert sequence IS26 and qacE of class I integron were found flanking the blaDHA-1 structural gene △ The expression isoelectric point of the recombinant bacteria was 7.7, and the drug susceptibility test showed resistance to cefoxitin, Conclusion the plasmid-mediated AmpC enzyme is DHA-1, and its adjacent insertion sequence IS26 is involved in the transfer of DHA-1.

Objective to study the therapeutic effect of adriamycin nano-liposomes (NLADR) administered by different routes on advanced rabbit breast carcinoma models. Methods NLADR was prepared by pH gradient drug loading method, with an average particle size of 120 nm. Fifty female New Zealand rabbits were randomly divided into 5 groups, 10 in each group, and VX2 breast transplant carcinoma model was prepared by tissue block suspension injection, and the treatment started at the 6th week after tumor transplantation. Group B: NLADR was injected subcutaneously around the tumor; Group C: NLADR was injected through the ear margin vein; Group D: NLADR was given intravenous and local injection at the same time, each accounting for 1/2 of the drug dosage; Group E: Adriamycin aqueous solution (FADR) was injected through the ear margin vein. In groups B, C, D and E, the single dose was 1 mg/kg, and the dose was repeated every 48 h. The animals were sacrificed 48 h after three treatments, and the transplanted tumors, axillary lymph nodes and all distant metastases were removed. The volume changes of the transplanted tumors and axillary lymph nodes were measured before and after treatment. The necrosis of the tumors was observed in pathological sections. The proliferating cell nuclear antigen (PCNA) was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the apoptosis of cancer cells was detected by terminal labeling (TUNEL). Results Intravenous injection of NLADR and FADR showed obvious inhibition on the metastases of tumors and lung and liver. Local injection of NLADR had significant curative effect on the metastases of axillary and mediastinal lymph nodes. Intravenous combined with local injection of NLADR had significant curative effect on the metastases of breast tumors, lymph nodes, lung and liver.

Objective to investigate the clinicopathological characteristics and rational treatment of intraductal carcinoma of the breast. Methods the clinicopathological data of 41 cases of intraductal carcinoma were collected and stained by immunohistochemistry. The labeled antibodies were ER, PR, proliferating cell nuclear antigen (PCNA), P53 and C-erbB-2. Results 15 cases of microinvasive intraductal carcinoma in this group, microinvasive and histological classification (χ 2=4.60, P<0.05) and tumor size (χ 2=9.78, P<The expression rates of ER, PR, PCNA, P53 and C-erbB-2 were 68.3%, 65.9%, 63.4%, 26.8% and 46.3%, respectively, which were not significantly different from those of invasive ductal carcinoma. The expression rates of ER, P53 and C-erbB-2 were correlated with histological types (χ 2=11.45, 11.97, 4.38, P<Conclusion Van Nuys histological classification is in accordance with the clinical treatment and prognosis, and individualized treatment should be carried out for intraductal carcinoma.

Objective to study the mutation sites and carrying status of BRCA1/BRCA2 gene in early-onset breast cancer in Shanghai, China.Methods Fifty cases of early-onset breast cancer (onset age ≤40 years) from Shanghai were studied.Among them, 13 cases (26%) had family history of first-degree relatives.Genomic DNA was extracted from venous blood, and all the coding sequences of BRCA1/2 gene were amplified. The mutation analysis was pre-screened by denaturing high performance liquid chromatography (DHPLC), and then confirmed by DNA sequencing.Results Six pathogenic mutation sites were found in BRCA1 gene, four of which were newly discovered sites, including two frameshift mutations (3449insA, 5587-1del8) and two splice point mutations (IVS17-1G>T, IVS21+1G>C). The two pathogenic mutation sites of BRCA2 gene were very close to each other on exon 11; One of the pathogenic mutations was frameshift mutation (5950delCT), and the other missense mutation (5911G>C) may be a new pathogenic mutation site. In addition, 12 new SNP sites were found, none of which caused amino acid coding changes; In early onset breast cancer, the mutation frequency of BRCA1 gene (12%) was higher than that of BRCA2 gene (4%); The frequency of BRCA1 gene mutation is 30.8% and 5.4% in patients with or without family history, respectively. Conclusion Four newly discovered pathogenic mutation sites of BRCA1 gene and one missense mutation site of BRCA2 gene may be unique mutation sites in early onset breast cancer in Chinese population; In Chinese population, BRCA1 gene mutation plays a greater role than BRCA2 gene mutation; This study provides a possible screening model for future clinical genetic testing.

Cerebral arteriovenous malformation (AVM) is a mass of arteries and veins intertwined with different structures. One or several fistulas are formed between the arteries and veins without capillaries. Blood can flow directly into the veins from the arteries through the arteriovenous fistulas and then back to the venous sinuses. Such abnormal changes in cerebral vascular structure and cerebral blood flow can lead to cerebral hemorrhage, cerebral steal hemorrhage and a series of brain dysfunctions, so active treatment must be carried out. According to the different levels of AVM, individualized treatment plan is formulated, and various methods combining embolization, radioneurosurgery and microsurgery are adopted, together with appropriate perioperative management, most cerebral AVM can obtain good therapeutic effect. 　　

A 23-year-old male was admitted to Beijing Sino-Japanese Friendship Hospital due to episodic convulsions 5 times. The patient appeared papules on his face and scalp shortly after birth, without self-conscious symptoms, and his intellectual development was acceptable. The patient's father could see papules around his mouth. Physical examination: scattered or densely distributed brown millet to rice-sized smooth papules on both cheeks and lips of the face, red patches scattered on the scalp and back, fading when pressed. Red papillary vegetation at the root of the right middle nail. 　　

Dacrymorrhea is a common disease in ophthalmology, mainly caused by lacrimal duct obstruction. Clinically, lacrimal duct obstruction mainly occurs in the nasolacrimal duct. nasolacrimal duct obstruction is divided into primary and secondary. Secondary nasolacrimal duct obstruction is mainly caused by trauma, surgery and tumor compression. However, the cause of primary nasolacrimal duct obstruction (PNDO) is not clear at present. Some studies have shown that bone lacrimal duct stenosis may be one of the causes of PNDO [1]. We used three-dimensional spiral CT to measure bone lacrimal duct, hoping to understand the morphology of bone lacrimal duct and judge whether there is an intrinsic relationship between the occurrence of PNDO and the anatomical structure of bone lacrimal duct. 　　

The prevalence of pheochromocytoma (PHEO) in hypertension ranges from 0.3% to 1.9% [1], of which malignant accounts for about 10% [2]. At present, there is no reliable index to distinguish benign and malignant PHEO. Therefore, exploring their different characteristics of clinical development can provide clinical basis for early diagnosis, treatment and prognosis. 　　

In recent years, angiotensin Ⅱ receptor antagonist (ARB) has become one of the commonly used antihypertensive drugs recommended in clinical hypertension treatment guidelines. Candesartan medoxomil is an ARB synthesized and produced in China, which can reduce the cost and facilitate patients. Therefore, the purpose of this study was to observe the efficacy, safety and tolerability of candesartan in the treatment of mild and moderate essential hypertension in China with enalapril as a control. 　　

Cytomegalovirus (CMV) infection is a common serious infection, which occurs in about 1% of infants. 10% of infants with congenital CMV infection have symptoms, and nearly half of them are related to clinically obvious neurological sequelae. In pregnant women with primary infection, the infection rate of fetus is 40% during pregnancy. Although congenital infection can be diagnosed before birth, there is no prenatal treatment at present, that is, there is no effective intervention for primary CMV infection during pregnancy. Nigro et al. conducted a very meaningful multicenter study on this, and the results were published in September 29<New England Journal of Medicine (N Engl J Med, 2005, 353: 1350-1362). 　　

A 23-year-old female was admitted to the hospital on June 8, 2004 after 17 weeks of menopause, with distension in the lower abdomen and vaginal bleeding for 18 days. At 40 days of menopause, the patient had early pregnancy reactions and felt fetal movement for 1 week. Due to abdominal distension and a small amount of vaginal bleeding, she had been admitted to the local hospital twice. Both considered "intrauterine pregnancy with partial hydatidiform mole" and recommended hospitalization to terminate the pregnancy. However, she was not admitted to the hospital because of severe distension in the lower abdomen, but without vaginal bleeding.