Therapeutic effect and clinical cost of multi-disciplinary team model of hepatoblastoma in children / 北京大学学报(医学版)

OBJECTIVE@#To summarize and analyze the treatment process, long-term efficacy and clinical economics of children's hepatoblastoma (HB) in multi-disciplinary team (MDT) mode, so as to provide basis for the rational choice of diagnosis and treatment.@*METHODS@#From January 2014 to February 2019, 13 cases of hepatoblastoma in children who completed the whole treatment course in the Pediatric Hematology Tumor Ward of Peking University First Hospital were collected and analyzed, and were followed up until June 30, 2020. There were 9 males and 4 females who were diagnosed and treated according to the MDT process in the hospital. The median age was 16 months (2-54 months), 69.23% (9/13) were under 2 years old. The characteristics, diagnosis and treatment process and treatment effect of the cases were summarized, and the cost of clinical treatment was analyzed.@*RESULTS@#According to the pretreatment extent of disease(PRETEXT), there were 1, 9 and 3 children with stages Ⅱ, Ⅲ and Ⅳ. 76.92% (10/13) of the patients had the largest tumor diameter > 10 cm. All the patients received preoperative neoadjuvant chemotherapy (8 patients received 4 cycles of chemotherapy, and 6 patients changed the chemotherapy plan), surgical treatment and postoperative chemotherapy, the tumor volume decreased by more than 50% (64%-95%) in 12 cases, except 1 case with no significant increase of alpha fetal protein and multiple lesions.The median length of stay was 87 days (68-214 days), the median cost of stay was 200 000 yuan (115 000-500 000 yuan), the median length of stay was 7 days (5-17 days), the median cost of stay was 20 000 yuan (15 000-60 000 yuan), and the incidence of postoperative complications was 7.69% (1/13). All the patients were followed up for 16-69 months. All the patients survived.@*CONCLUSION@#Under the MDT mode, the treatment is seamless connection, the long-term prognosis of children with HB is good, and the total hospitalization cost and time are within the acceptable range. Standard preoperative neoadjuvant chemotherapy can significantly reduce the tumor, improve the resection rate, reduce postoperative complications, reduce the total individual expenditure, shorten the total hospital stay, and further improve the long-term disease-free survival rate.

Distribution characteristics and risk factors of human papillomavirus infection in cervical intraepithelial neoplasia in Shanxi Province / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the distribution characteristics and risk factors of HPV infection in the cervical intraepithelial neoplasia(CIN)cohort in Shanxi Province.METHODS: From June to December 2014,40,000 married women under the age of 65 years in Shanxi were screened for cervical cancer,and the abnormal cervical fluid-based cytology(TCT)was excluded.Gland microscopy and histopathological examination were performed.Finally a total of 2304 women were included in the study.Questionnaires were used to collect demographic characteristics and factors related to cervical cancer,and HPV typing was performed by flow-through hybridization.RESULTS: Among the 2304 subjects,the HPV infection age range was 36-40 years old;the top 5 HPV infection rates were HPV16/58/52/53/51.The top 5 HPV infectionrates in CIN2 及 以 上 were HPV16/58/31/33/52. HPV single infection accounted for 23.13%,multiple infection accounted for 9.51%,and with the increase of cervical lesion,degree HPV single infection rate and multiple infection rate also increased.Multivariate analysis showed that the risk of HPV infection in those who were educated for ≤ 9 years was 1.236 times(95% CI 1.029-1.484)of those who were educated for >9 years;the risk of HPV infection in the women with non-menstrual use of pads was 1.328 times(95% CI 1.016～1.736)of menopausal women,the risk of HPV infection in non-menopausalwomen was 2.407 times of those without(95% CI 2.012-2.880).CONCLUSION:s The high-risk age of HPV infection in Shanxi is 36-40 years old;the most common type of HPV infection is HPV16/58/52/53/51;the most pathogenic type is HPV16,58,31,33,52,whose distribution characteristics are different from those of other areas;short-term education,non-menopause,and non-menstrual use of pads are high-risk factors for HPV infection.

Role of vaginal microbial metabolites and enzymes and high risk HPV in the development of cervical intraepithelial neoplasia / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the role of vaginal microbial metabolites and enzyme changes and high-risk human papillomavirus(HR-HPV)infection in cervical intraepithelial neoplasia(CIN)and their interaction effects.METHODS: From June 2014 to December 2014,demographic characteristics and CIN-related factors and cervical liquid-based cytology(TCT)examination results were collected from 40 000 community-based populations from two regions of Shanxi Province by the Second Hospital of Shanxi Medical University.Patients who meet the criteria for enrollment were further tested for vaginal microecology,HPV testing,and colposcopic and pathologic examination.A total of 782 cases with pathological diagnosis of CIN were chosen as the case group;1503 patients with normal pathological results were chosen as a control group.A multivariate logistic regression model was established to analyze the vaginal microbial metabolic enzymes cross-sectionally,then the association between vaginal microbial metabolic changes and CIN risk was evaluated.RESULTS: The expression of hydrogen peroxide(H2 O2),β-glucuronidase(GUS)and sialidase(SNA)was statistically correlated with CIN risk,and the odd ratios were 1.60(95% CI 1.30-1.96),1.58(95% CI 1.30-1.92),and 1.45(95% CI1.18-1.79),respectively.The expression of acetylglucosaminidase(NAG)and leukocyte esterase(LE)had no statistical association with CIN risk.Interaction analysis showed that there were positive multiplicative interactions among H2 O2,GUS,SNA and HR-HPV infections in the occurrence of CIN.CONCLUSION: Positive H2 O2,GUS,and SNA is associated with increased risk of CIN,and they have positive interaction with HR-HPV infection,which increases the risk of CIN.

Congenital renal arteriovenous fistula complicated with multiple renal arteries malformation: case analysis / 北京大学学报(医学版)

Congenital renal arteriovenous fistula complicated with multiple renal arteries malformation is rare and hard to diagnose at early stage. Blood loss and complications after embolization are both severe. Some cases can be diagnosed by ultrasound, enhanced CT scan or digital subtraction angiography (DSA). Cystoscopy and ureteroscopy can identify the location of bleeding, exclude tumors, and discharge ureteral obstruction. A case of congenital renal arteriovenous fistula complicated with multiple renal arteries malformation was reported to investigate the pathogenesis, clinical characteristics, diagnosis and treatment of congenital renal arteriovenous fistula with multiple renal arteries malformation. A 36-year-old female patient with congenital renal arteriovenous fistula with multiple renal arteries malformation was hospitalized in the Department of Urology of Peking University People's Hospital. Five days before admission, the patient experienced whole course painless gross hematuria for 5 days with many blood clots. The patient's blood pressure was 90/70 mmHg, and hemoglobin was 60 g/L. The urinary CT scan showed a right hydronephrosis associated with dilatation of the upper ureter which was obstructed by space occupying lesion of the lower ureter. Many clots in the bladder could also be found in the CT scan. Cystoscopy showed many blood clots in the bladder and confirmed that the bleeding was fromthe right ureteral orifice. Ureteroscopy confirmed that the bleeding was from the right renal pelvis and many blood clots in the right ureter, and found no tumor in the right ureter and renal pelvis. We cleared the blood clots in the right ureter and inserted a ureteral stent.We thought that renal vascular malformation of the right kidney might lead to the hematuria from right renal pelvis. DSA showed a double renal arteries malformation in the right kidney. The diagnosis of "renal arteriovenous fistula" was considered with renal arteriovenous fistula in the right kidney. Selective arteriography revealed the presence of tortuous, coiled, dilated, and multichannelled vessels in the middle of the right kidney. With stainless steel coils, we embolized the vessels which supplied the fistula. Four days after the procedure, gross hematuria disappeared. Five days after the procedure, the patient's anemia improvedand the patient was discharged in good condition. Four months after the procedure, gross hematuria did not recur. The Doppler showed that the right kidney was normal and the renal dynamic showed that the right kidney function was normal. So DSA is the golden standard for diagnosis of congenital renal arteriovenous fistula complicated with multiple renal arteries malformation. Confirming the number of renal arteries by abdominal aorta angiography is necessary to avoid missed diagnosis. Renal arterial embolization is safe and effective.

Minimal fat renalangiomyolipoma with multiple lymph nodes enlargement and postoperative refractory lymphatic fistula: a case report and literature review / 北京大学学报(医学版)

Renal angiomyolipoma (AML) is a common benign tumor in the urinary system, mainly composed of adipose tissue, blood vessels and muscle tissue. Renal AML is sporadic in most of patients, while a few are associated with tuberous sclerosis. Classical renal AML occurs predominantly in middle-aged females. Most cases are found incidentally during imaging examinations. The fat content makes AML have unique imaging characteristics and is easy to be identified with other renal tumors. However, the amount of fat varies in each tumor. AML that contains only microscopically detectable fat and whose amount of intratumoral fat may be too small to be identified on unenhanced computed tomography (CT) images is termed minimal fat or fat-poor renal AML, which appears as a high density shadow in the renal parenchyma on unenhanced CT images. Thus, it can be difficult to distinguish it from renal cell carcinoma (RCC) on imaging. Since the imaging findings are atypical, the diagnosis depends on pathological results. In addition, a few of AML can mimic malignant neoplasms. Recent studies suggested that AML might involve to peri-renal or renal sinus fat, regional lymphatics and other visceral organs, as well as inferior vena cava, which further makes the diagnosis more difficult. However, there is currently no reports about involvement of regional limphatics in minimal fat renal AML. In this article, we report a 27-year-old female patient without family history of tuberous sclerosis, who came to visit the hematologist because a high density shadow near the left kidney was found during CT scan which was accompanied by neck, armpits, groin, abdominal cavity and retroperitoneal lymph nodes enlargement. She was suspected of lymphoma in the beginning and transferred to Department of Urology to perform laparoscopic left renal mass and retroperitoneal lymph node excision and pathological examination for a definitive diagnosis. Finally, pathologic results revealed AML. Postoperative continuous lymphatic fistula developed and the retroperitoneal drainage of chylous fluid was 100-200 mL per day, lasting for 12 weeks. The fistula was successfully closed after conservative treatment including fasting and rehydration. This article summaries and discusses the diagnosis and treatment of renal AML with lymph nodes enlargement and the management of postoperative refractory lymphatic fistula by reviewing the related cases and literature.

Clinical characteristics analysis of children with reversible posterior leukoen-cephalopathy syndrome during the treatment of hematological tumor / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical characteristics of patients with hematological tumor or disease before and after reversible posterior leukoen-cephalopathy syndrome (RPLS).@*METHODS@#Five patients were both from Peking University First Hospital Pediatric Hematology-oncology Department in the period from March 2012 to March 2017. The gender, age, BMI, underlying diseases, with or without renal damage, hypertension family history, clinical manifestations of convulsions, hemoglobin, and blood pressure, serum sodium levels before and after convulsion, and other data of the children with RPLS were retrospectively analyzed. In the meantime, we followed up the five patients for 6 months to 66 months, kept a watchful eye on their original condition and the recovery of symptoms and signs of the nervous system. The relevant literature was reviewed.@*RESULTS@#All of the subjects were females in school-age or pre-school age. The underlying diseases were malignant tumor associated with renal involvement or on one side of nephrectomy in 4 of these subjects, while the other one was refractory autoimmune hemolytic anemia. All of the subjects suffered from mild or moderate anemia. The day before RPLS occurred they received chemotherapy made up with cyclophosphamide, vincristine, and actinomycin-D, or the therapy with cyclosporin A and glucocorticoid. The clinical manifestations were afebrile convulsion after getting up in the mooring or in the afternoon. We observed elevation of blood pressure and cutting down of serum sodium compared with themselves. All of the cases recovered soon after management with diazepam, furosemide and amlodipine besylate. Four of them had a good outcomes and did not remain any sequela, while only one girl became childish in emotion and behavior, and then returned gradually to normal two years later. However, by long-term follow-up, the elevation of blood pressure was mainly reviewed in literature.@*CONCLUSION@#The patients attacked by RPLS, with hematology or oncology cases, could have the underlying disease of renal damage and anemia. Blood pressure elevation and serum sodium falling down at the same time may play an important role during the occurrence of RPLS. Remaining stable of blood pressure and electrolyte level together will possibly reduce or mitigate RPLS.

Influence of SOX10 on the proliferation and invasion of prostate cancer cells / 北京大学学报(医学版)

OBJECTIVE@#To explore the influence of SOX10 on the proliferation and invasion of prostate cancer cells.@*METHODS@#SOX10 protein in prostate cancer cell lines PC3, DU145 and LNcap was detected by Western blotting analysis. The expression of SOX10 in prostate cancer cell lines (PC3 and DU145) were knocked down by small interfering RNAs, and the efficiency of SOX10 by small interfering RNAs was confirmed using Western blotting analysis. CCK-8 assays were conducted to assess the influences of SOX10 on the proliferation of PC3 and DU145 cells, and invasion assays were conducted to assess the influences of SOX10 on the invasion of PC3 and DU145 cells.@*RESULTS@#After SOX10 in prostate cancer cells was knocked down by small interfering RNAs, the proliferation of prostate cancer cells PC3 and DU145 was significantly inhibited. Results of CCK-8 assays showed that the absorbance of PC3 and DU145 in SOX10-silenced groups was decreased compared with those in control groups (PC3: 0 d: 0.166±0.01, 0.162±0.012 vs. 0.155 ±0.01, P>0.05; 1 d: 0.210±0.011, 0.211±0.018 vs. 0.252±0.023, P>0.05; 2 d: 0.293±0.017, 0.280±0.028 vs. 0.433±0.030, P<0.01; 3 d: 0.363±0.071, 0.411±0.038 vs. 0.754±0.045, P<0.01; 4 d: 0.592±0.065, 0.670±0.093 vs. 1.456±0.111, P<0.01. DU145: 0 d: 0.168±0.018, 0.164±0.01 vs. 0.153 ±0.012, P>0.05; 1 d: 0.218±0.007, 0.206±0.024 vs. 0.255±0.02, P>0.05; 2 d: 0.297±0.013, 0.291±0.012 vs. 0.444±0.023, P<0.05; 3 d: 0.378±0.058, 0.419±0.026 vs. 0.762±0.039, P<0.01; 4 d: 0.681±0.094, 0.618±0.050 vs. 1.419±0.170, P<0.01). Meanwhile, knocking down SOX10 significantly suppressed the invasion of prostate cancer cells PC3 and DU145. Results of invasion assays showed that the numbers of invaded cells in SOX10-silenced groups were significantly less than those in control groups (PC3: 142±38, 171±17 vs. 304±55; DU145: 96±22, 134±23 vs. 341±34, P<0.05).@*CONCLUSION@#SOX10 might promote prostate cancer progression by accelerating the ability of the proliferation and invasion of prostate cancer cells, and SOX10 might be a potential therapeutic target for prostate cancer.

Relationship between large artery elasticity function and coronary heart disease, lower extremity arterial disease in patients with carotid plaque / 北京大学学报(医学版)

Objective:To evaluate the relationship between large artery elastic function and coronary heart disease (CHD) or lower extremity arterial disease (LEAD) in patients with carotid plaque.Methods:A total of 491 patients with carotid plaque were enrolled into the study with complete data of arterial stiffness detection and blood test [male:208 and female:283,and mean age:(61.66 11.60) years].All the subjects were divided into 2 groups according to CHD or LEAD,namely non-CHD&LEAD group (neither CHD nor LEAD) and CHD/LEAD group (either CHD or LEAD).According to the mean age level (age ＜61.66 years or age ＞61.66 years),the independent association was analyzed between higher large arterial stiffness (carotid-femoral pulse wave velocity,CF-PWV,CF-PWV ＞ 9 m/s) and CHD/LEAD.Results:In the present research population,the mean level of arterial stiffness was high (the mean CF-PWV was 10.71 m/s),and 76.6％ of them had arteriosclerosis,and 36.9％ CHD/LEAD.The age,male and smoking proportion,systolic blood pressure (SBP),glycosylated hemoglobin (HbA1c),homocysteine (Hcy),creatinine (Cr),CF-PWV,prevalence rate of hypertension and diabetes mellitus,medication on hypertension,diabetes and hyperlipidemia were higher in CHD/LEAD group,and total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),and low density lipoprotein cholesterol (LDL-C) were lower in CHD/LEAD group than in non-CHD&LEAD group (all P ＜ 0.05).In multivariate Logistic regression analysis,the results showed that in the patients with age below 61.66 years,large artery stiffness (CF-PWV ＞ 9 m/s) was an independent risk factor of CHD/LEAD (OR =3.229,95％ CI 1.156-9.022,P ＜ 0.05);In the patients with age above 61.66 years,there was no independent association between large artery stiffness and CHD/LEAD (P ＞ 0.05).Conclusion:The large artery elasticity function in the patients with carotid plaque was poor.In the patients with carotid plaque and higher large artery stiffness below 61.66 years,the risk of the prevalence of CHD/LEAD was increased significantly than with normal arterial stiffness.In the patients with carotid plaque below or above 61.66 years,the independent influencing factors on the prevalence of CHD/LEAD were different.

A rhabdomyosarcoma patient from a Li-Fraumeni syndrome family: a case report and literature review / 中国当代儿科杂志

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, with the characteristics of early onset of cancer and high cancer incidence. TP53 is widely accepted as a pathogenic gene of LFS. A 2 years and 6 months old boy is reported in this article, who was diagnosed with embryonal rhabdomyosarcoma (RMS) in the left submandibular region. His brother died of RMS, and his grandmother was diagnosed with breast cancer. TP53 gene mutation detection was performed in this patient and some family members, indicating a missense mutation in exon 8 of the patient: c.844C>T (p.Arg282Trp, heterozygous). TP53 mutation was also found in his mother and sister. The boy met the diagnostic criteria for LFS. Among pediatric patients, the most common LFS diseases include osteosarcoma, adrenocortical cancer, central nervous system tumor, and soft tissue tumor. Additionally, leukemia and lymphoma are also involved. LFS patients have a high risk to suffer secondary or even multiple cancers. Therefore, it is necessary to perform genetic detection for pediatric cancer patients, especially those with hereditary predisposition cancers. TP53 mutation often indicates poor prognosis, so it is important to take active treatment and systematic monitoring for LFS family.

Adverse effects of high-dose methotrexate therapy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the adverse effects of high-dose methotrexate (HDMTX) therapy, and to provide a theoretical basis for optimizing clinical treatment.</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of 120 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma who underwent 601 times of HDMTX therapy. The adverse effects of various systems were analyzed according to the WHO criteria for the classification of adverse effects of anticancer drugs.</p><p><b>RESULTS</b>Almost all the children experienced bone marrow suppression, and 93.3% had granulocytopenia. The most common adverse effects in the digestive system and urinary system were elevated glutamic-pyruvic transaminase (60.4%) and proteinuria (9.2%) respectively. For skin symptoms, skin erythema had the highest incidence rate (7.2%). The adverse effects in the nervous system (hyperpathia, numbness of extremities, or headache) were only observed in 7 cases. Serious adverse effects were only seen in the blood system and digestive system. Compared with the 3 g/mmethotrexate (MTX) group, the 5 g/mHDMTX group had a significantly higher 24-hour plasma MTX concentration, significant reductions in hemoglobin and platelet count, and significantly higher incidence rates of oral mucositis, proteinuria, and skin symptoms (P<0.05).</p><p><b>CONCLUSIONS</b>Serious adverse effects of HDMTX therapy mainly involve the blood system and digestive system, and the adverse effects such as bone marrow suppression, oral mucositis, proteinuria, and skin symptoms occur in a dose-dependent manner.</p>

Antidepressant activities of flavonoids from Glycyrrhiza uralensis and its neurogenesis protective effect in rats / 药学学报

Adult rats chronic unpredictable stress model of depression (CUS) was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract (licorice flavonoids, LF) from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids (300 mg x kg(-1), 100 mg x kg(-1) and 30 mg x kg(-1)) for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5'-Bromo-2'-deoxyuridine (BrdU) labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids (300 mg x kg(-1)) can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone (SGZ) of dentate gyrus (DG) region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti-depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.

Investigation on individualized adjustment of target range of high-dose methotrexate / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the way of individualized adjustment of target range of each high-dose methotrexate (MTX) 24 hours infusion to treat acute lymphoblastic leukemia in children.</p><p><b>METHODS</b>Twenty-four children and 105 infusions were included in the study. According to 1 h and 6 h plasma MTX concentrations after infusion, based on established high-dose MTX population pharmacokinetics model, the course predicted value of drug concentration at steady state (C(SS)) was calculated. MTX infusion rate and dosage was adjusted 8 h after the start according to the predicted value of C(SS). Then MTX concentration at 23 h (actual value of C(SS)) was measured.</p><p><b>RESULTS</b>To achieve the target range of C(SS), adjustments of MTX dosage were required in 17 (71%) patients. Adjustments of MTX dosage were required in 45 (43%) infusions, the dose was increased in 42 infusions and decreased in 3 infusions. There were 29 infusions of high-dose MTX during consolidation therapy (after remission induction therapy). Among them, 16 infusions had increased dosage, and 1 infusion had decreased dosage. There were 76 infusions during maintenance therapy. Among them, 26 infusions increased dosage, and 2 infusions decreased dosage. Overall 95 (90%) infusions achieved the target range of C(SS), while in 8 infusions the doses were lower than the target range in 2 infusions the doses were higher than the target range. If there had been no adjustments, only 74 (70%) infusions could have achieved the target range. Adjustments of MTX dosage, compared with no adjustments, could remarkably enhance the rate of achieving the target range of C(SS) (chi(2) = 13.366, P = 0.000). Among 60 infusions of no adjustments, the actual values of C(SS) were well correlated with the predicted values of C(SS) (r = 0.487, P = 0.000), and the actual values of C(SS) were also correlated with the 6 h plasma MTX concentrations after infusions (r = 0.389, P = 0.002). The actual values of total clearance (CL) of MTX of 105 infusions were 7.01 +/- 2.06 L/(m(2).h). Inter-courses variability in CL was up to 4.4-fold. Intra-patient variability in CL was up to 2.9-fold. Predisposing factors that correlated with decreased CL of MTX were old age, heavy body weight, low blood phosphate, high blood bilirubin and infusions during maintenance therapy (P < 0.05).</p><p><b>CONCLUSIONS</b>High-dose methotrexate chemotherapy needed individualized adjustment, as inter-courses variability of CL was up to 4.4-fold among 105 infusions. According to 1 h and 6 h plasma MTX concentrations after infusion, adjusting MTX infusion rate and dosage, overall 90% infusions achieved the target range of C(SS). High-dose MTX infusions during consolidation therapy needed individualized adjustment of target range more.</p>

Clinicopathological characteristics and prognostic factors of breast cancer with estrogen- and progesterone-receptor negative and HER-2 overexpression / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the clinicopathological characteristics and prognosis of breast cancer with estrogen- and progesterone-receptor negative (ER-/PR-) and HER-2 overexpression (HER+++) in a Chinese population.</p><p><b>METHODS</b>The data of patients with ER-/PR- and HER+++ breast cancer treated in our hospital from March 1999 to December 2004 were retrospectively reviewed. The influence of clinicopathological characteristics and molecular markers on the survival was analyzed.</p><p><b>RESULTS</b>A total of 111 breast cancer patients with ER and PR negative but HER+++ were identified, accounting for 4.9% of all the breast cancer patients treated during the same period. There were 25 cases (22.5%) in stage I, 44 (39.6%) in stage II and 36 (32.4%) in stage III, respectively, with a median age of 49 years. Axillary lymph node metastasis was found in 54 cases. The 5-year disease free survival (DFS) and overall survival rates (OS) were 70.7% and 73.1%, respectively. Univariate analysis showed that lymph node status, primary tumor size and pathological stage were prognosis-related factors influencing the DFS and OS. However, by multivariate analysis, only primary tumor size and lymph node status were independent factors influencing survival.</p><p><b>CONCLUSION</b>The breast cancer with estrogen- and progesterone-receptor negative but HER-2 overexpression is a particular subtype of breast cancers, with unfavorable clinicopathological characteristics and poor survival. Lymph node status and primary tumor size are two independent prognostic factors.</p>

Clinical characteristics and prognosis of breast cancer patients with vascular invasion / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathological features, parameters of molecular biology, survival rate, and prognostic factors in breast cancer patients with vascular invasion.</p><p><b>METHODS</b>The data of 262 breast cancer patients with vascular invasion surgically treated between January 1995 and December 2003 in our institution were retrospectively analyzed. Clinicopathological characteristics, parameters of molecular biology, disease free survival rate and overall survival rate were surveyed.</p><p><b>RESULTS</b>Of all breast cancer patients registered in our institution during the same period, these 262 breast cancer patients with vascular invasion accounted for 5.3% with a median age of 43 years. The major pathological type was invasive ductal carcinoma (93.3%). The stages included stage I in 5% , stage II 31. 3% , stage III 58.8% , stage IV 1.1% , and unknown 3.8%. Immunohistochemical staining showed that ER positive in 67.7%, PR(+) 68.0%, p53(+) 54.2%, PCNA(+) 93.3%, c-erbB2( +++) 20.8% and c-erbB2(++) 16.9%. The 5-year and 10-year cumulative disease free survival and overall survival were 57.6% , 50.7% and 62.8%, 52.9% , respectively. The factors which were found to compromise disease free survival were the tumor size, lymph node status, stage, and radiotherapy in the univariate analysis, and for overall survival, were the tumor size, lymph node status, stage, location of vascular invasion and radiotherapy. The tumor size and radiotherapy were found to be independent prognostic factors for disease free survival and overall survival in the multivariate analysis.</p><p><b>CONCLUSION</b>Breast cancers with vascular invasion have poor biological behavior though having been treated by surgery, radiotherapy and chemotherapy. The independent prognostic factors of such patients are tumor size and radiotherapy. Anti-angiogenesis and antilymphangiogenesis may gradually become promising target treatment for such patient.</p>

Adeno-associated virus-mediated CD40 ligand transfer into human lung cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the transduction efficiency of serotype 1, 2, 5, 6, 7, 8, 9, 10 recombinant adeno-associated viruses (rAAV) in human lung cancer cell line A549 cells and compare the transduction efficiency of conventional AAV vectors with that of self-complementary AAV (scAAV) vectors. Furthermore, the capacity of A549 cells expressing transgenic CD40L to stimulate dendritic cells (DCs) was evaluated.</p><p><b>METHODS</b>Lung cancer A549 cells were infected with 1 x 10(4) particules per cell of AAV encoding the green fluorescent protein (GFP) or human CD40L driven by CMV promotor, and transgene expression was analyzed by flow cytometry and fluorescence microscopy. Stimulation of isolated human dendritic cells by CD40L-expressing tumor cells was quantified by measuring secreted interleukin-12 with immunoassay.</p><p><b>RESULTS</b>Serotype AAV2/5 transduced A549 cells much more efficiently than serotypes AAV2/1, AAV2/2, AAV2/6, AAV2/7, AAV2/8, AAV2/9 and AAV2/10. The transduction efficiency of scAAV2/5 was significantly higher than that of conventional AAV2/5. Furthermore, pre-treatment with carboplatin substantially increased AAV-mediated transgene expression. The scAAV2/5 vectors encoding human CD40L was used to generate CD40L. A549 cells transduce by these vectors were co-cultured with immature human DCs. As a consequence, interleukin-12 was released and measured in the culture supernatant. Specificity of immunostimulatory effect of CD40L was confirmed by blocking with a monoclonal antibody binding to human CD40L.</p><p><b>CONCLUSION</b>scAAV2/5 transduce lung adenocarcinoma A549 cell efficiently, and co-administration of chemotherapeutic agent carboplatin further enhances its transduction efficiency. It is confirmed that lung cancer cells infected with a CD40L-encoding scAAV2/5 construct can activate human DCs to secrete interleukin-12. Our findings provided a basis for future immunotherapeutic approaches including intratumoral transfer of stimulating factors.</p>

Expressions of LRP, GST-pi and MRP1 in acute leukemia patients and its clinical significance / 中国实验血液学杂志

This study was purposed to investigate the relationship of expressions of gluthatione-S-transferase-pi (GST-pi), multidrug resistance protein-1 (MRP-1), lung resistance protein (LRP) with multidrug resistance of acute leukemia (AL), the correlation between 3 kinds protein expressions and the correlation of their protein expression with clinical features of AL patients. The S-P immunohistochemical staining method was used to determine the expressions of GST-pi, MRP1 and LRP proteins in 80 AL patients and 30 normal subjects. The results showed that there was the correlation between GST-pi, MRP1, LRP protein expression and chemotherapy resistance, meanwhile CR rates of patients with positive expression of those proteins were lower than that of patients with negative expression (P<0.05), so those protein expressions may be accounted for poor prognosis. There was the positive relationship between expression of GST-pi and MRP1 in refractory group (r=0.851, P<0.01). It is concluded that co-examination of GST-pi and MRP1 has greater significance than examination of one kind of protein in evaluating poor prognosis of leukemia patients. LRP protein expression increase obviously when WBC counts >or= 10 x 10(9)/L (63.6%, P<0.05), therefore LRP protein has great judging value for evaluating drug resistance and prognosis of acute leukemia patients whose peripheral blood WBC counts were high.

Clinical features and prognosis in breast cancer patients over 70 years of age / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and prognostic factors in breast cancer patients over 70 years of age.</p><p><b>METHODS</b>From 1980 to 2003, 280 female breast cancer patients over 70 years old were treated and the data were retrospectively reviewed. The clinical features including age, comorbidity, initial symptom, tumor size and location, pathological type, lymph node status, hormonal receptor status, treatment approaches and overall survival were analyzed.</p><p><b>RESULTS</b>These 280 patients accounted for 2.9% of all breast cancer patients registered in our institution during the same period. Presentation of breast lump as initial symptom accounted for 92.5% of the patients. The median time from the presentation of initial symptom to initial diagnosis was 4 months. Major pathological type was invasive ductal carcinoma (74.3%). Estrogen or progesterone receptor was found to be positive in 72.9% by immunohistochemical staining. 165 patients (58.9%) had comorbidity such as coronary heart disease, hypertension, diabetes, etc. 256 patients underwent surgery consisting of 162 modified mastectomies, 46 mastectomies, 38 lumpectomies, 7 lumpectomies plus lymph node dissection, 2 lymph node resection and 1 with unavailable surgery record. The cumulative 5- and 10-year overall survival was 69.9% and 40.6%, respectively. Factors affecting the prognosis were tumor size, lymph node status, pathological stage, vascular invasion and endocrine therapy by univariate analysis. The lymph node status and vascular invasion were found to be two independent prognostic factors affecting significantly the prognosis by multivariate analysis.</p><p><b>CONCLUSION</b>Female breast cancer patients over 70 years of age exhibit distinctive clinical and pathological characteristics. Surgery and endocrine therapy are important to achieve good clinical outcome. Lymph node status and vascular invasion are two independent prognostic factors.</p>

Cholesterol concentrations in cord blood of newborn infants / 中华儿科杂志

<p><b>OBJECTIVE</b>Familial hypercholesterolemia (FH) is an autosomal dominant disease with an estimated worldwide prevalence of 0.2%. It is caused by a multitude of low density lipoprotein receptor gene mutations. It is characterized with high levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and a high incidence of coronary artery disease in young adults. Cord blood cholesterol concentration is used for mass screening of FH. The purpose of this study was to detect the lipid levels of cord blood in newborn infants from China and to determine the cut-off point after 1 to 2 years follow-up.</p><p><b>METHODS</b>TC, triglycerides (TG), LDL-C and high density lipoprotein cholesterol (HDL-C) were determined in 242 healthy full-term newborn infants.</p><p><b>RESULTS</b>The mean values of TC, TG, LDL-C and HDL-C in cord blood were (1.69 +/- 0.40) mmol/L, (0.23 +/- 0.12) mmol/L, (0.81 +/- 0.21) mmol/L and (0.58 +/- 0.16) mmol/L (mean +/- standard deviation), respectively. The HDL-C concentration in male neonates was lower than that in female neonates (P < 0.05).</p><p><b>CONCLUSION</b>After the follow-up of 1 to 2 years for FH, the recommended screening cut-off points were TC > or = 2.47 mmol/L and LDL-C > or = 0.89 mmol/L.</p>

Impact of human urotensin II on the pulmonary arterial smooth muscle cells cycle in normoxic/hypoxic rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the impact of human urotensin II (hUII) on pulmonary arterial smooth muscle cell (PASMCs) cycle in vitro.</p><p><b>METHODS</b>PASMCs dissected from Wistar rats were cultured in vitro, and incubated with series of concentrations of hUII (10(-7) mol/L, 10(-8) mol/L, 10(-9) mol/L) for 12 hours under normoxia or hypoxia condition, in order to analyze cell cycle progression and sub-G1 of PASMCs by using flow cytometric analysis stain of propidium iodide, which represented the proliferative and apoptotic changes in PASMCs.</p><p><b>RESULTS</b>The study showed a dose-dependent effect of hUII on PASMCs proliferation, which reflected the increase both in percentage of S phase of cell cycle and proliferative index (PI). The response of PASMCs to hUII was different under normoxic and hypoxic conditions. Compared with the control group, the treatment of 10(-7) mol/L, 10(-8) mol/L and 10(-9) mol/L hUII produced an increase of 175%, 136% and 118% under normoxia, respectively, and 135%, 118% and 103% under hypoxia, respectively. The concentration 10(-7) mol/L hUII played a significant role in PASMCs proliferation both under hypoxia and normoxia (P < 0.01). The results of cell cycle did not show sub-G1 of PASMCs at various concentrations of hUII.</p><p><b>CONCLUSION</b>hUII may stimulate DNA synthesis in S phase cell cycle of PASMCs and the proliferation of PASMCs under normoxia and hypoxia conditions, which promote cell growth in a dose-dependent manner.</p>

Concentrations of Methotrexate Elimination after High Dose Infusion and Its Influencing Factors / 实用儿科临床杂志

1 ?mol?L-1,and it was defined as "delayed" MTX elimination.Intra-patient variability in C48 was significant(P=0.000).Risk factors that correlated with increased C48 of MTX were boys,abnormal urine routine tests within 1 week before infusions,concurrent infections within 2 weeks before infusions,and co-administration of ceftriaxone(P