Volume 86  ·   Issue 42  ·  2006

Hematopoietic stem cell transplantation (HSCT) and solid organ transplantation have saved the lives of thousands of patients, but in recent years, it has been found that some patients have developed lymphocytic proliferative disease (PTLD) after transplantation. PTLD has been reported abroad in 1990s. With the increase of the number of transplanted people and the improvement of the understanding of PTLD, the number of cases has increased year by year. This issue publishes 4 cases of PTLD reported by Liu Qifai's research group, which indicates that domestic scholars have also paid attention to the clinical characteristics of this kind of disease. The incidence of PTLD in HSCT patients accounts for about 1.3%, and 43 cases of PTLD were found in a large sample of 3372 HSCT cases, with an incidence rate of 1.28%. The peak incidence of PTLD is 1.4% 10 years after transplantation. The incidence rate of PTLD in solid organ transplantation patients is about 2%. This year, a large multi-center study in the United States reported that more than 5% of children who received heart transplantation developed PTLD, and the death from PTLD is equivalent to that of failed organ transplantation [1].

With the popularization of hematopoietic stem cell transplantation (HSCT) and the improvement of related techniques, the efficacy of transplantation has improved obviously, but infection is still one of the common complications and main causes of death. The treatment of infection, especially the treatment of severe infection, has become a major problem affecting the efficacy of transplantation. The efficacy of antibiotics not only depends on the antibacterial spectrum of antibiotics and the type of pathogens, but more importantly, the immunity of the body. HSCT complicated infection has its peculiarity and complexity, the pathogens and infection foci are often unclear, the clinical manifestations are often atypical, the detection rate of pathogens in culture is low, and immunosuppressants and graft-versus-host disease (GVHD) are often used. The immunity of the body is extremely low, the efficacy of conventional treatment is poor, and the disease progresses quickly and the mortality rate is high, so it is urgent to control it quickly. Therefore, according to the characteristics of HSCT infection, it is particularly important to study and formulate corresponding countermeasures.

The etiological diagnosis of "fever of unknown origin" (FUO) is a worldwide problem in the field of internal medicine. So far, nearly 10% of FUO patients can't finally identify the etiology. The etiology of this disease is complicated, involves many systemic lesions, and can't be clearly classified. Most tertiary hospitals are mainly treated by respiratory physicians. In recent years, the number of doctors and departments treating such patients has increased, one of the reasons is that fever itself can involve diseases in many disciplines, such as infectious diseases, oncology, respiratory department, rheumatology, hematology, etc. At present, many hospitals have opened infectious diseases departments, and FUO is focused on the diagnosis (treatment) of infectious diseases department. This specialized management is a kind of progress, which can improve the diagnosis and treatment level. Since about 50% of FUO is caused by various pathogens, and many infectious diseases also have fever as the first or one of the main symptoms, infectious diseases physicians have more perceptual understanding of the diagnosis and treatment of diseases with fever as the main manifestation. However, we must also clearly realize that the infectious diseases department after the renaming, Its medical staff are still classic infectious disease workers. On the one hand, they lack systematic training in the diagnosis and treatment of other internal diseases. On the other hand, most infectious diseases departments still mainly treat infectious diseases and even hepatitis patients. The diagnosis and treatment of FUO patients still needs to accumulate further experience and improve the level.

Objective to investigate the time-dependence between the efficacy of surgical treatment and prognostic factors in patients with hepatocellular carcinoma with portal vein tumor thrombus. Methods the clinicopathological factors of 381 patients with hepatocellular carcinoma with portal vein tumor thrombus were analyzed. The survival rate was calculated by Kaplan-Meier method. The prognostic factors affecting survival were analyzed by Cox regression stratification method. Results the overall 1, 2, 3, 5 and 10-year survival rates of 381 patients were 47%, 23%, 16%, 12% and 6%, respectively. The recalculated 1, 3 and 5-year survival rates after reoperation were 36%, 14% and 0 for patients with recurrent intrahepatic tumor within 2 years, respectively. 85%, 53% and 32% respectively (P<0.05). Multivariate analysis showed that portal vein perfusion chemotherapy, serum alpha-fetoprotein<20 μ g/L and negative surgical margin were important favorable prognostic factors within 2 years after surgery, while alanine aminotransferase>80 U/L was the only important adverse prognostic factor after 2 years after surgery. Conclusion The prognosis of patients with hepatocellular carcinoma with portal vein gross tumor thrombosis after 2 years of surgery is significantly better than that of patients with recurrence within 2 years.

Objective to analyze the reasons for delayed diagnosis and treatment of primary hyperaldosteronism adrenal adenoma and explore the coping strategies.Methods The clinical data of 267 cases of primary hyperaldosteronism adrenal adenoma confirmed by surgery in Peking Union Medical College Hospital in the past 10 years were retrospectively analyzed, and the relevant parameters were statistically processed.Results All 267 cases had a history of hypertension for 3~40 years.Among the newly diagnosed hospitals, 78.3% were secondary hospitals, 21.7% were tertiary hospitals.95.9% were newly diagnosed with primary hypertension without relevant adrenal imaging and endocrine examination, which led to the diagnosis delay.All patients had hypokalemia manifestations for 2~9 years.Among them, 87.3% were diagnosed as hypokalemia by blood biochemical examination at follow-up.The rest cases were not tested for blood potassium.The interval between initial diagnosis and diagnosis was (92±64) months. 151 cases were suspected of adrenal tumors by ultrasonography, and 267 cases were found by enhanced thin-slice CT scan.Conclusion Secondary factors should be excluded in young adults with hypertension, It is necessary to do endocrine examination related to original aldehyde. Plasma aldosterone concentration/renin ratio is an effective means of screening. Clinicians should pay attention to the causes of hypokalemia and improve their analytical ability. The first choice for localization is thin-slice CT scan plus enhancement of adrenal region.

Objective to study the similarities and differences of pathogenic gene mutations in familial and sporadic hypertrophic cardiomyopathy (HCM) patients in China. Methods MYH7 missense mutations were found in 36 HCM patients and 50 sporadic HCM patients in 10 families, namely G12601A mutation in exon 18 (Arg663His), G15373A mutation in exon 23 (Glu924Lys), and T13659C mutation in exon 20 (Ile736Thr). Among 50 sporadic HCM patients, T13659C mutation in exon 20 of MYH7 was found in 1 case. No TNNT2 gene mutation was found in all HCM patients. MYBPC3 gene mutation was found in 4 cases in 2 families of familial HCM patients: 2 cases with 18 Conclusion MYH7 and MYBPC3 may be one of the main pathogenic genes of familial HCM in China, but the mutation rate of MYH7 and MYBPC3 is low in sporadic HCM patients in China. TNNT2 may not be the main pathogenic gene in HCM patients in China.

Objective to investigate the effect of shenfu injection on hypoxic-ischemic brain injury (HIBD) in neonatal rats. Methods A model of HIBD in neonatal rats was established, and the experiment was divided into two parts: (1) to observe the body weight changes of neonatal rats in each group at 3, 7, 14 and 28 days after hypoxic-ischemia and the survival rate within 28 days of each group. (2) to measure the apoptosis rate of neurons in the hippocampal CA1 region of neonatal rats at each time point 2 h before hypoxic-ischemia and 2 h, 12 h, 24 h, 3 d, 7 d, 14 d and 28 d after hypoxic-ischemia by flow cytometry. Each group was randomly divided into four groups (20 rats in each group): sham operation group, normal saline control group, shenfu pretreatment group and shenfu treatment group. Results At 3, 7, 14 and 28 days after hypoxic-ischemia, the body weight gain of normal saline control group was significantly lower than that of sham operation group (7 d: 8.8 g ± 2.1 g vs 14.0 g ± 2.9 g, all P<0.01), and significantly lower than that of shenfu pretreatment group (7 d: 11.7 g ± 3.3 g, P<0.01 or P<0.05). The survival rate of the normal saline control group was 60% (12/20), the survival rate of the Shenfu pretreatment group was 90% (18/20), and the survival rate of the Shenfu treatment group was 85% (17/20). The survival rate of the normal saline control group was significantly lower than that of the other groups (P<0.05), and the survival rate of the other groups was not statistically significant (all P>0.05). The apoptosis rate of hippocampal neurons in the normal saline control group, the Shenfu treatment group and the Shenfu pretreatment group began to increase 2 h after hypoxia-ischemia, and began to decrease after reaching a peak 24 h after hypoxia-ischemia, and then decreased to normal 14 d after hypoxia-ischemia. The apoptosis of hippocampal neurons in the Shenfu treatment group and the Shenfu pretreatment group was significantly better than that in the normal saline control group (24 h: 16.0%±4.2% vs 11.9%±2.3% vs 18.1%, P<0.05 or P<0.01). Conclusion Shenfu injection reduced the occurrence of neuronal apoptosis after hypoxia-ischemia in neonatal rats, improved the growth and development of neonatal rats after HIBD, and improved the survival rate.

Objective to establish a clinicopathological sampling method suitable for endoscopic mucosal dissection and resection, so as to improve the detection rate of early colorectal carcinoma. Methods Colorectal neoplastic lesions specimens undergoing endoscopic mucosal dissection and resection were examined by routine colonoscopy in Nanfang Hospital from August to December 2005. The suspected cancerous lesions exceeding 10 mm were observed by mucosal staining and solid microscope. According to the type of glandular duct opening, the suspected cancerous sites were judged for targeted pathological examination, and the influence on the detection rate of colorectal carcinoma was observed by comparing with the routine random samples. At the same time, the detection rate of early colorectal carcinoma at this stage was compared with the detection rate of random samples in 2004. Results Mucosal staining and solid microscope were used for targeted sampling. Among the 40 suspected cancerous cases, 16 cases were diagnosed with early cancerous changes (including severe dysplasia). After these 16 samples were randomly collected and submitted for examination, except 1 case with severe dysplasia, The other 15 cases were mild or moderate atypical hyperplasia.In the same period of 2004, non-targeted samples were taken, and only 4 cases of early cancer (including severe atypical hyperplasia) were detected in 54 suspected colorectal tumors, with a detection rate of 7.4%. Conclusion Targeted localized biopsy of mucosal staining solid microscope can improve the detection rate of early colorectal cancer.

Objective to observe the annual bone loss rate of different bone parts and its relationship with menopausal time in women in osteoporosis prevention and treatment community of Mawangdui Township, Changsha City.Methods The bone mineral density (BMD) of lumbar spine, hip and distal radius of 220 women aged 36-60 years was measured by DXA QDR 4500A fan-beam bone densitometer. After 3.9-4.1 years, the bone mineral density was re-measured to determine the annual bone loss rate. L1-L4 (AP) of anterior and posterior lumbar spine and trochanter of hip had significant bone loss in perimenopausal group; Bone loss was fastest in the early menopausal group, and the annual bone loss rates of AP, femoral neck, trochanter major and distal radius were 1.70%, 2.21%, 1.92% and 1.56%, respectively; There was a positive correlation between age and the annual bone loss rates of AP, trochanter major and distal radius in postmenopausal women (γ =0.223~0.547, P<0.05~0.01). There was a positive correlation between menopausal age and the annual bone loss rates of AP and trochanter major in postmenopausal women (γ =0.432~0.569, P<0.05~0.01). Body weight and body mass index were negatively correlated with the annual bone loss rates of AP, femoral neck and trochanter major in postmenopausal women (γ =0.239~0.466, P<0.05~0.01). Conclusion There are differences in the annual bone loss rates in different bone parts. Age, menopausal age and body weight affect the bone loss in different bone parts.

Objective to detect serum protein in children with nephroblastoma, screen specific protein markers, and construct a serum protein fingerprint model for early diagnosis of nephroblastoma. Methods The protein mass spectra of 75 serum samples (30 cases of nephroblastoma, 25 cases of other pediatric solid tumors and 20 cases of normal children) were detected by surface-enhanced laser dissolution ionization time-of-flight mass spectrometry (SELDI-TOF-MS), and the data were analyzed by bioinformatics method (support vector machine). Results Four protein markers with mass-to-charge ratios (m/z) of 6984.5, 6455.5, 6914.0 and 3256.7 were screened, and the early diagnosis model of nephroblastoma was constructed. The specificity of serum protein fingerprint model to distinguish nephroblastoma from other solid tumors is 100%, and the sensitivity is 93.3%. Conclusion the establishment of serum protein fingerprint model of nephroblastoma by surface enhanced laser dissolution ionization time-of-flight mass spectrometry combined with support vector machine is a new method with strong specificity and high sensitivity for early diagnosis of nephroblastoma, and can be used for early diagnosis of nephroblastoma and screening of tumor markers.

Objective to establish a spectral karyotype analysis technique (SKY) and to explore the application value of SKY in leukemia. Methods SKY technique was established in 2 healthy volunteers. SKY technique was established in 8 leukemia patients who had undergone R-banding karyotype analysis. Four of them were also detected by double fusion fluorescence in situ hybridization (DF-FISH) of MLL, PML/RARa and BCR/ABL genes, respectively. The results of R-banding karyotype and DF-FISH were compared to investigate the stability and reliability of SKY technique. Results SKY analysis was successful in 10 samples. Two healthy volunteers showed normal karyotype. In 8 leukemia patients, SKY analysis showed 9q-, t (9; 22), t (15; 17), and complex karyotype 47, XY, +9? ins (1; 5) (q23; q23), t (6; 7) (q23?; p13) and some quantitative anomalies.These results confirm the conclusions of R banding and DF-FISH, and have more accurate localization and complement.Conclusion The spectral karyotyping technique established in this study has high stability,reliability and accuracy,and can be applied to the chromosome study of leukemia.

Post-transplantation lymphoproliferative disease (PTLD) is a rare fatal complication after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT). Four cases of PTLD were found in patients who underwent hematopoietic stem cell transplantation in Nanfang Hospital of Southern Medical University from 2001 to 2005, and are reported below.

Objective to analyze the gene polymorphism of human leukocyte antigen (HLA) system in hematopoietic stem cell donors in Shaanxi and identify new HLA alleles. Methods HLA genotyping techniques such as sequence-specific primer polymerase chain reaction (PCR-SSP), PCR-sequence-specific oligonucleotide probe (SSO) flow microbead detection and DNA sequencing (SBT) were used to detect HLA gene polymorphism in 14 006 hematopoietic stem cell donors in Shaanxi.Results A total of 18, 40 and 15 HLA-A, B and DRB1 alleles (including serological specificity) were detected in 14 006 unrelated donors, including HLA-A25, B42, B53, B73 and DR3.HLA-A·02, A·11, A·24, A·33, B·13, B·46, B·4001 (B60), B·1501 (B62), DRB1·15, DRB1·09, DRB1·04 and DRB1·12, which were rarely detected in Han population.

Objective to investigate the role of matrix metalloproteinase 9 (MMP-9) in the mobilization of hematopoietic stem/progenitor cells (HSPC) induced by granulocyte colony-stimulating factor (G-CSF). Methods the changes of MMP-9 protein and mRNA levels in bone marrow and peripheral blood of healthy donors at homeostasis and on the fifth day of G-CSF mobilization were measured by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). The changes of CXCR4 expression on CD34+ cells and the migration ability of stromal cell-derived factor 1 (SDF-1) were compared before and after incubation with serum-free supernatant of MMP-9-rich cell line HT1080. After incubation with rhMMP-9 and rhSDF-1, the degradation of SDF-1 by MMP-9 was detected by Western blot. The effects of injection of MMP-9 chemical inhibitor (MPI) o-phenanthrene on the mature leukocyte count (WBC) and the number of stem/progenitor cells in peripheral blood of G-CSF-mobilized BALB/c mice were observed. MMP-9 mRNA expression in bone marrow mononuclear cells was up-regulated after mobilization (P<0.05). rhSDF-1 and rhMMP-9 were degraded by the latter after short-term incubation. HT1080 serum-free culture supernatant could up-regulate the expression level of CXCR4 in CD34+ cells enriched in umbilical cord blood and mobilized peripheral blood (both P<0.05) and enhance the ability of CD34+ cells to migrate to SDF-1 concentration gradient (both P<0.05). This effect could be blocked by MPI (P<0.05). After co-injection of MPI with G-CSF, the number of mature WBC (12.3×106/L ± 1.2×106/L) and hematopoietic progenitor cell colony-forming units (69 U/2×105 MNC ± 3 U/2×105 MNC) in peripheral blood of BALB/c mice was significantly lower than that in the control group (P<0.05). Conclusion MMP-9 may up-regulate the expression of SDF-1 specific receptor CXCR4 on the surface of CD34+ cells by lysing SDF-1

Objective to investigate the role of natural killer cell immunoglobulin-like receptor (KIR) in umbilical cord blood transplantation. Methods Twenty-three cases of leukemia treated with umbilical cord blood transplantation were summarized. The genotyping of human leukocyte antigen (HLA) -C allele and KIR genotyping in peripheral blood and umbilical cord blood were detected by sequence-specific primer polymerase chain reaction (PCR-SSP) genotyping method. The implantation viability and long-term survival rate of KIR were followed up to analyze the effect and effect of KIR on umbilical cord blood transplantation. Results The expression of KIR gene in 23 donors showed polymorphism by detection. In 17 myeloid leukemia groups, the implantation viability and long-term survival rate were higher (64% vs 50%, 73% vs 50%), and the recurrence rate was lower (9% vs 16%) if the KIR inhibitory receptor and its ligand HLA-C were not matched between donors and recipients. Conclusion KIR and its ligand HLA-C play an important role in the treatment of leukemia by umbilical cord blood transplantation. The donor and recipient KIR/HLA-C mismatch group, the patients with HLA-Cw1 or HLA-Cw2 subset deletion group, and the donor KIR2DL2 and KIR2DS2 double expression group suggest good prognosis.

A 15-year-old woman diagnosed with accelerated chronic myeloid leukemia underwent father-to-woman human leukocyte differentiation antigen (HLA) 4/6 compatible bone marrow and peripheral blood hematopoietic stem cell transplantation (HSCT) in our hospital in April 2004. The pretreatment regimen of Maryland, cyclophosphamide and anti-T lymphocyte immunoglobulin (modified BuCy + ATG) was used.

Solid organ transplantation is the only effective treatment for all kinds of end-stage diseases or solid organ failure at present. Although the incidence of hematological complications after transplantation is low, once they occur, they will seriously affect the recovery of patients after operation and even threaten their lives. Anemia is a common clinical hematological complication after solid organ transplantation, with many types, complicated etiology and difficult diagnosis and treatment. pure red cell aplasia (PRCA) is a special type of anemia, which is characterized by bone marrow erythroid hematopoietic disorder and normal granulocyte and megakaryocyte [1]. It is usually abbreviated as "pure red cell aplasia". This disease is rare, accounting for about 3% of the total aplastic anemia. In recent years, there are more and more reports about PRCA after solid organ transplantation abroad [2, 3]. There are many etiologies of PRCA after transplantation, and the pathogenesis is not very clear. This article discusses the related articles on the etiology, pathogenesis, diagnosis, treatment and prevention of PRCA after solid organ transplantation abroad in recent years

The patient was a 21-year-old female who was diagnosed with acute myeloid leukemia (AML) -M2. The human leukocyte antigen matching was completely compatible with that of the patient who was a healthy donor at that time. The allogeneic bone marrow transplantation (BMT) was completed in August 2003. Before BMT, the donor received granulocyte colony stimulating factor (G-CSF, Terzin, Xiamen Tebao Company) 5 μ G · kg-1 · d-1 for 3 days, and 1280 ml of bone marrow fluid was donated on the fourth day. After the transplantation, her brother was in continuous remission, the routine peripheral blood and bone marrow morphology examination were normal, and the chromosome and DNA STR examination still showed complete donor type implantation.

The Department of Hematology of the First Affiliated Hospital of Zhengzhou University treated 17 cases of refractory and relapsed acute leukemia with topotecan (TPT) + etoposide (VP16) + mitoxantrone (MTZ) combined with induction chemotherapy (TEM regimen), and achieved good curative effects, which are reported below.

Coronary atherosclerotic heart disease (CAD) in the course of coronary atherosclerosis, vascular endothelial cell function and various related factors changes, especially the changes of platelet, coagulation and fibrinolytic factors activities, the individual response to the changes of vascular factors (including the rupture of atherosclerotic plaque) is more dependent on the plasma level of coagulation and fibrinolytic factors.

It has been confirmed that Barrett's esophagus (BE) is closely related to the occurrence of esophageal adenocarcinoma and some cardiac carcinoma, and is a precancerous lesion.The increase of the incidence of BE in the population has become the direct cause of the large increase of the incidence of esophageal adenocarcinoma and cardiac carcinoma in western countries in recent years.Therefore, the study of BE has attracted much attention abroad in recent decades.In recent years, there are also reports of the increase of the incidence of esophageal adenocarcinoma and cardiac carcinoma in China.At present, it is generally believed that gastroesophageal reflux is the main cause of BE forming.However, in recent years, some scholars have suggested that bile salts in duodenal fluid are more important in the occurrence and development of BE. Therefore, in this experiment, 24-h intraesophageal pH and Bilitec synchronous monitoring technology was used to monitor BE, reflux esophagitis (RE), non-erosive reflux disease (NERD) and control groups. The characteristics of reflux in each group were compared, and the factors affecting the length of BE mucosa were discussed.

Helicobacter pylori (Hp) infection has been recognized as an important pathogenic factor of chronic gastritis, peptic ulcer and gastric cancer. Effective eradication of Hp is of great significance for preventing the occurrence of Hp-related diseases. At present, there is no ideal drug that is simple, effective, economical, has no toxic side effects, has good patient compliance and low drug resistance rate. People have been trying to find more ideal new anti-Hp drugs that meet the above requirements. Studies have confirmed that chitosan has a broad spectrum of antibacterial effects [1,2] and immunomodulatory effects, and it can regulate the balance of Th1 and Th2 responses [3]. Therefore, it may play a role in the immunopathological damage caused by Hp infection, thus alleviating the inflammatory response caused by Hp infection, which will be superior to the classical triple and quadruple antibiotic therapy. However, there are few studies on the anti-Hp effect of chitosan, and previous studies have confirmed that it has anti-Hp effect in vitro [4,5]. This study further observed the anti-Hp effect of chitosan in vivo and its effect on gastric mucosal inflammation.