Apheresis practice variation during the COVID-19 pandemic: Results of a survey.

BACKGROUND: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. STUDY DESIGN AND METHODS: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. RESULTS: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. CONCLUSION: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.

Successful treatment of retinopathy of prematurity in oculocutaneous albinism with OCA2 variants: a case report and review of literature.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of autosomal recessive hereditary disorders that affect melanin biosynthesis, resulting in abnormalities in hair, skin, and eyes. Retinopathy of prematurity (ROP) is a proliferative retinopathy mainly observed in premature infants with low birth weight and early gestational age, but it can also affect full-term infants or children with normal weight, particularly in developing countries. The coexistence of ROP and OCA is rare. There is limited documentation regarding treatment approaches, with few studies reporting positive outcomes with laser treatment due to the absence of melanin pigment. This study discusses the treatment challenges in a female infant diagnosed with ROP and OCA, and underscores the importance of genetic analysis in guiding therapeutic decisions for this rare comorbid condition. CASE PRESENTATION: The study presents a case of ROP occurring concurrently with OCA. Genetic testing revealed two variants, c.727C > T (p.R243C) and c.1832 T > C (p.L611P), in the OCA2 gene, inherited from the patient's mother and father, respectively. The identified mutations were consistent with a diagnosis of OCA2, classified as a subtype of OCA. The patient initially received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection, followed by laser photocoagulation therapy for a recurrent event. A favorable outcome was observed during the 2-month follow-up period. CONCLUSIONS: The co-occurrence of ROP and OCA is a rare phenomenon, and this is the first recorded case in the Chinese population. The current case supports the use of laser as the primary treatment modality for ROP in OCA2 patients with partial pigmentation impairment. Furthermore, genetic analysis can aid in predicting the effectiveness of laser photocoagulation in this patient population.

A retrospective study for association between post-transfusion hemoglobin S level and pre-transfusion hemoglobin S level at the next scheduled transfusion.

BACKGROUND: Patients with sickle cell disease (SCD) frequently undergo prophylactic red blood cell (RBC) exchange transfusion and simple transfusion (RCE/T) to prevent complications of disease, such as stroke. These treatment procedures are performed with a target hemoglobin S (HbS) of ≤30%, or a goal of maintaining an HbS level of <30% immediately prior to the next transfusion. However, there is a lack of evidence-based instructions for how to perform RCE/T in a way that will result in an HbS value <30% between treatments. PRINCIPAL OBJECTIVE: To determine whether targets for post-treatment HbS (post-HbS) or post-treatment HCT (post-HCT) can help to maintain an HbS <30% or <40% between treatments. MATERIALS AND METHODS: We performed a retrospective study of patients with SCD treated with RCE/T at Montefiore Medical Center from June 2014 to June 2016. The analysis included patients of all ages, and data including 3 documented parameters for each RCE/T event: post-HbS, post-HCT, and follow-up HbS (F/u-HbS), which is the pre-treatment HbS prior to the next RCE/T. Generalized linear mixed model was used for estimating the association between post-HbS or post-HCT levels and F/u-HbS <30%. RESULTS: Based on our results, targeting post-HbS ≤10% was associated with higher odds of having events of F/u-HbS <30% between monthly treatments. Targeting post-HbS ≤15% was associated with higher odds of events of F/u-HbS < 40%. As compared to post-HCT ≤30%, a post-HCT >30%-36% did not contribute to more F/u-HbS <30% or HbS <40% events. CONCLUSIONS: For patients with SCD undergoing regular RCE/T for stroke prevention, a post-HbS ≤10% can be used as a goal to help maintain an HbS <30% for 1 month, and a post-HbS ≤15% allowed patients to maintain HbS <40%.

Apheresis physician well-being during the COVID-19 pandemic: Results of a survey.

BACKGROUND: The COVID-19 pandemic has placed additional stressors on physician lives. In this study, we report findings from a survey conducted among attending physician (AP) members of the American Society for Apheresis (ASFA) to elucidate the status of their well-being during the COVID-19 pandemic as well as resources provided or actions taken by their institutions and themselves personally to maintain or improve their well-being. STUDY DESIGN AND METHODS: A 17-question, voluntary, IRB-approved survey regarding well-being was distributed to the ASFA AP members between August 26, 2020 and September 16, 2020. The descriptive analyses were reported as number and frequency of respondents for each question. Non-parametric chi-square tests, ANOVA, and paired t-tests were performed to determine differences in categorical variables, changes in well-being scores, and compare time points, respectively. RESULTS: Based on the responses of 70 attending level physicians representing the United States (U.S., 53, 75.7%) and outside the U.S. (17, 24.3%), the following were observed: (1) COVID-19 negatively affects the well-being of a sub-population of APs, (2) neither institutional nor individual measures to improve well-being completely resolved the problem of decreased AP well-being during the pandemic, and (3) personal actions may be superior to institutional resources. CONCLUSION: There is a widespread decline in AP well-being during the COVID-19 pandemic that was not adequately improved by institutional or personal resources/actions taken. Institutions and physicians must work together to implement strategies including resources and actions that could further improve AP physician well-being during a public health crisis.

Apheresis medicine in the era of advanced telehealth technologies: An American Society for Apheresis position paper Part I: Understanding the basic technologies and apheresis medicine practice models.

The wide spread availability and use of sophisticated high-speed telecommunication networks coupled with inexpensive and easily accessible computing capacity have catalyzed the creation of new tools and strategies for healthcare delivery. Such tools and strategies are of value to apheresis medicine (AM) practitioners if they improve delivery of patient care, enhance safety during a therapeutic apheresis (TA) intervention, facilitate care access, advance technical capabilities of apheresis devices, and/or elevate quality performance within TA programs. In the past several years, healthcare delivery systems' adoption of telecommunication technologies has been fostered by organizational financial and quality improvement objectives. More recently, adoption of telehealth technologies has been catalyzed by the COVID-19 pandemic as these technologies enhance both patient and provider safety in an era of social distancing. These changes will also influence the delivery of TA services which now can be generally viewed in a tripartite model format comprised of traditional hospital-based fixed site locales, mobile TA operations and lately an evolving telemedicine remote management model now reffered to as telapheresis (TLA). This communication developed by the Public Affairs and Advocacy Committee of the American Society for Apheresis (ASFA) and endorsed by its Board of Directors, reviews and describes various aspects of established and evolving electronic technologies related to TLA and the practice of AM. In subsequent companion publications, additional aspects to TLA will be explored and ASFA's vision of reasonable, regulatory compliant and high-quality TLA practices will be expounded.

Impact of Patient Blood Management on Red Blood Cell Utilization in an Urban Community Teaching Hospital: A Seven-Year Retrospective Study.

OBJECTIVES: This study aimed to showcase how implementing a patient blood management (PBM) program effectively cuts unnecessary red blood cell (RBC) transfusions in a New York City urban community teaching hospital. METHODS: Analyzing seven years from 2013 to 2019, a retrospective review of RBC transfusions was conducted. RESULTS: Following the introduction of PBM, considerable improvements were observed annually. These included a drop in mean pretransfusion hemoglobin levels from 7.26 g/dL (2013) to 6.58 g/dL (2019), a 34% reduction in yearly RBC unit transfusions, and fewer units given to patients with pre-Hgb levels ≥ 7 g/dL (from 1210 units in 2013 to 310 units in 2019). Furthermore, this study noted a decline in two-unit RBC orders when Hgb levels were ≥ 7 g/dL from 65 orders in 2013 to merely 3 in 2019. The estimated total cost savings attributed to the six-year PBM program duration after full implementation in 2014 amounted to USD 2.1 million. CONCLUSIONS: Overall, PBM implementation significantly decreased RBC transfusions and enhanced transfusion practices. The findings emphasize that successful PBM strategies do not always necessitate extensive resources or increased budgets but instead rely on the application of intuitive methods, as evidenced by this study.

[Methylation analysis of CpG island DNA of FMR1 gene in the fragile X syndrome].

OBJECTIVE: To establish a method of methylation-sensitive restriction enzymes based quantitative PCR (MSRE-qPCR) for analysis of CpG island DNA of FMR1 gene, and to assess its value for molecular diagnosis of fragile X syndrome. METHODS: Thirty boys with mental retardation and abnormal repeats of 5'(CGG)n in the FMR1 gene and 20 mothers were analyzed by conventional PCR screening. Eag I was used to digest genomic DNA, and qPCR was performed to amplify CpG island in the FMR1 gene using both undigested and digested templates. Raw Ct values were obtained through quantitative PCR amplification. The degree of CpG island methylation was calculated by 2 - U+0394 U+0394 Ct. The result of MSRE-qPCR was verified by Southern blotting. 30 healthy females and 30 healthy males were used as controls to optimize the established MSRE-qPCR method. RESULTS: The ranges of 2 - U+0394 U+0394 Ct value for normal methylation, partial methylation and full methylation were determined. Among the 30 patients, 3 were found to have partial methylation of CpG island of the FMR1 gene, and 27 were found to have full methylation (3/30 results were verified by Southern blotting). Only 7 mothers were found abnormal methylation of CpG island of FMR1 gene, whilst the remaining 13 mothers were normal. CONCLUSION: MSRE-qPCR is a quick and reliable method for quantitative analysis of CpG island methylation status in FMR1 gene, which may provide a new strategy for the diagnosis of fragile X syndrome.

A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China.

BACKGROUND: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. METHODS: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. RESULTS: We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. CONCLUSIONS: We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients.

Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone (AMH) gene or the anti-Müllerian hormone receptor type 2 (AMHR2) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as "pathogenic" or "likely pathogenic", and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.

Spatiotemporal expression of PSD-95 in Fmr1 knockout mice brain.

To investigate and compare the spatial and temporal expression of post-synaptic density-95 (PSD-95) in Fmr1 knockout mice (the animal model of fragile X syndrome, FXS) and wild-type mice brain, on postnatal day 7 (P7), P14, P21, P28 and P90, mice from each group were decapitated, and three principal brain regions (cerebral cortex, hippocampus and cerebellum) were obtained and stored for later experiments. PSD-95 mRNA in the three brain areas was analyzed with quantitative RT-PCR. PSD-95 protein was measured by immunohistochemical staining and Western blot. In the three principal brain areas of Fmr1 knockout mice and wild-type mice, the expression of PSD-95 mRNA and protein were detected at the lowest levels on P7, and then significantly increased on P14, reaching the peak levels in adolescents or adults. Moreover, it was found that PSD-95 mRNA and protein in the hippocampus were significantly decreased in Fmr1 knockout mice during the developmental period (P7, P14, P21 and P28) as well as at adulthood (P90) (P < 0.05, and P < 0.01, respectively). However, there was no significant difference of expression of PSD-95 in the cortex and cerebellum between Fmr1 knockout and wild mice. The expression of PSD-95 in the hippocampus might be regulated by fragile X mental retardation protein (FMRP) during mice early developmental and adult periods. It is suggested that impairment of PSD-95 is possibly involved in hippocampal-dependent learning defects, which are common in people with FXS.

[Clinical and genetic analysis of a pedigree of Kennedy disease].

OBJECTIVE: To review the clinical and genetic features of a pedigree of Kennedy disease in China. METHODS: The clinical data of patients from a Kennedy disease family were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis. RESULTS: In the pedigree, 4 patients were identified as Kennedy disease. Clinical manifested with adult-onset, progressive proximal limb muscle weakness and atrophy, gynecomastia, oligospermia were also presented. The number of trinucleotide CAG repeats in exon 1 of the androgen receptor gene was 51 in the proband. The electrophysiological study showed sensory and motor involvement and their serum triglycerides values were elevated significantly. CONCLUSION: Androgen receptors gene testing is the most reliable diagnosing method, the patients suspected as Kennedy disease should have a gene testing of androgen receptors.

[Relationship between 22q11 microdeletion syndrome and congenital heart disease].

OBJECTIVE: To investigate the relationship between 22q11 microdeletion syndrome and congenital heart disease. METHODS: Clinical screening assessment and genetic testing using standard fluorescence in-situ hybridization (FISH) were applied in 207 subjects suspected for 22q11 microdeletion syndrome. Patients with 22q11 microdeletion syndrome were examined by echocardiography, patients with complicated congenital heart disease were examined further by cardiac catheterization. RESULTS: 22q11 microdeletion syndrome was detected in 39 subjects. The incidence of 22q11 microdeletion syndrome was 1.6% in suspects with simple congenital heart disease without extracardiac manifestations, 53.0% in suspects with congenital heart disease combined with at least two extracardiac manifestations, 3.8% in suspects without congenital heart disease. The incidence of congenital heart disease in 22q11 microdeletion syndrome patient and non 22q11 microdeletion syndrome patient was 94.9% and 54.2% (P < 0.01). The incidence of congenital heart disease combined with at least two extracardiac manifestations in 22q11 microdeletion syndrome patient and non 22q11 microdeletion syndrome patient was 89.7% and 18.5% (P < 0.01). In 22q11 microdeletion syndrome patients, Tetralogy of Fallot was the most common type of congenital heart disease. Dysmorphic faces, learning difficulties and retarded physical development were the most common extracardiac manifestations of the congenital heart disease patients. CONCLUSION: 22q11 microdeletion syndrome is related to congenital heart disease.

FMR1 allele frequencies in 51,000 newborns: a large-scale population study in China.

BACKGROUND: Fragile X syndrome (FXS), caused by CGG-repeat expansion in FMR1 promoter, is one of the most common causes of mental retardation. Individuals with full mutation and premutation alleles have a high risk of psychophysiological disorder and of having affected offspring. Frequencies of FMR1 alleles in general newborns have been reported in Caucasians but have not been investigated in the large-scale population in  the mainland of China. METHODS: The sizes of FMR1 CGG-repeats were analyzed in 51,661 newborns (28,114 males and 23,547 females) and also in a cohort of 33 children diagnosed with developmental delay using GC-rich polymerase chain reaction (PCR) and triple repeat primed PCR. RESULTS: The frequency of CGG repeats > 100 was 1/9371 in males and 1/5887 in females, and the frequency of CGG repeats > 54 was 1/1561 in males and 1/1624 in females. FMR1 full mutation and premutation were identified in 27.27% of children who had Ages and Stages Questionnaire scores less than two standard deviations from the cutoff value. CONCLUSIONS: Our study revealed the prevalence of FXS in China and improved the sample databases of FXS, suggesting that the prevalence of FXS in Chinese is higher than estimated previously and that FXS screening can be advised to high-risk families.

A novel TFG c.793C>G mutation in a Chinese pedigree with Charcot-Marie-Tooth disease 2.

INTRODUCTION: Mutations within TFG gene were recently reported to cause Charcot-Marie-Tooth disease 2 (CMT2). However, only few pedigrees were documented so far. Here, we reported a Chinese CMT2 pedigree with 8 affected cases and a novel TFG mutation. METHODS: Clinical evaluation and electrophysiological study were performed in all the affected individuals. Whole-exome sequencing was conducted, followed by the Sanger sequencing and co-segregation analysis to verify the variants. RESULTS: All cases presented with a phenotype of CMT2, including slowly progressive symmetrical muscle atrophy and weakness predominantly in the distal limbs. Sensory loss in the distal limbs was present in the proband and his father. Age at onset ranged from 37 to 44 years, and was younger in male cases, compared with female cases. Nerve conduction study revealed normal motor nerve conduction velocity but decreased compound muscle action potential. Electromyography test revealed fibrillation potential and positive sharp waves. The creatine kinase activity was increased in all cases. After genetic investigations, we identified a novel TFG c.793C>G (p.Pro265Ala) mutation in the family. This mutation alters the conserved amino acid residue and is absent in 1000G, ExAC, dbSNP, EP6500, and 200 in-house controls. It co-segregated with the disease in the family. CONCLUSIONS: Our report provided additional evidence that the heterozygous TFG mutations were associated with CMT2.

Spontaneous mutation of hemoglobin Lufkin in a white boy.

A 10-year-old white boy presented clinically with thalassemia major facies, pallor, jaundice, and hepatomegaly. Investigation revealed the patient has hemoglobin (Hb) Lufkin concurrent with beta(0) thalassemia. DNA sequencing of the beta globin gene confirmed a GGC to a GAC mutation at codon 29 (gly to asp) for Hb Lufkin on the patient and also revealed a beta(0) thalassemia mutation, IVS-1-1 (G to A), on both the patient and his mother. Both parents lack the Hb Lufkin mutation. Molecular studies, human leukocyte antigen, and red blood cells phenotypic studies indicate spontaneous mutation of Hb Lufkin in this patient.

Impact of Prothrombin Complex Concentrate on Blood Use, Cost, and Outcomes in Heart Transplantation.

BACKGROUND: Left ventricular assist device (LVAD) recipients undergoing heart transplantation have increased bleeding risk. We compared conventional warfarin reversal with fresh frozen plasma vs 4-factor prothrombin complex concentrate (PCC) and the effect on transfusion requirements, blood bank costs, and clinical outcomes. METHODS: A retrospective review identified 60 consecutive LVAD recipients undergoing heart transplantation divided into two groups: 30 (no PCC) received fresh frozen plasma and 30 (PCC) received PCC. Patient characteristics, intraoperative and postoperative transfusion requirements, short-term clinical outcomes, and blood bank costs were compared. PCC association with transfusion requirements was assessed by multivariate linear regression. RESULTS: Patients who received PCC were younger (50 ± 11 vs 57 ± 13 years, p = 0.02), fewer had ischemic cardiomyopathy (23% vs 60%, p = 0.01), had more than one prior sternotomy (7% vs 30%, p = 0.04), and had higher preoperative hemoglobin (11.8 ± 1.8 vs 10.4 ± 1.8 g/dL, p = 0.01). The PCC group had a significantly shorter bypass time (185 vs 217 minutes, p = 0.01), received less fresh frozen plasma (2 vs 5 units, p = 0.03), cryoprecipitate (0 vs 2 units, p = 0.05), and total blood products (9 vs 13.5 units, p = 0.03) intraoperatively, and was less likely to require delayed sternal closure (3% vs 23%, p = 0.05). On multivariate linear regression, PCC was significantly associated with decreased intraoperative transfusion (ß = -6.09, p = 0.02). There was no difference in thromboembolic events or in-hospital death. Total blood bank costs were $4,949 for PCC and $3,677 for no PCC (p = 0.01). CONCLUSIONS: Although more costly, PCC reduced transfusion requirements and delayed sternal closure in heart transplant recipients bridged with LVAD, justifying its use over traditional warfarin reversal.

[The clinical features and gene mutation analysis in a pedigree of spinocerebellar ataxia type 7].

We investigated the clinical features and gene mutation in a pedigree of spinocerebellar ataxia (SCA). A series of clinical tests was performed including visual examination, retinal angiography, visual evoked potential, electroretinogram and magnetic resonance imaging. Genomic DNA of the family members and normal controls was used for amplification of the (CAG)n repeats of SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA genes by PCR. The number of (CAG)n was determined by 8% denaturing polyacrylamide gel electrophoresis and direct sequencing. The main features of 2 patients were ataxia, visual failure, retinal degeneration, cerebellar and pontine atrophy. A mutation in SCA7 gene was detected, while no mutations were found in SCA1, SCA2, SCA3, SCA6, SCA17 or DRPLA gene. Therefore, this is a pedigree of SCA7. Analysis of the CAG trinucleotide repeat expansion at the SCA7 locus can provide valuable insights into SCA7.

[Quantities of human papillomavirus 16 E6 mRNA and its relationship with expression of survivin in cervical cancer].

OBJECTIVE: To investigate the quantities of human papillomavirus (HPV) 16 E6 gene and to study its relationship with the expression of survivin in cervical carcinoma. METHODS: In 148 patients including cervical intraepithelial neoplasia (CIN), cervical carcinoma and chronic cervicitis, the quantities of HPV 16 E6 gene were detected by semiquantitative polymerase chain reaction (PCR); and the expressions of survivin were measured by immunohistochemical streptavidin-biotin peroxidase (SP) assay. RESULTS: The quantities of HPV 16 E6 gene were 0.3 +/- 0.4, 0.6 +/- 0.4, 1.8 +/- 0.6 and 2.4 +/- 0.6, and expression rates of survivin were 7%, 31%, 63% and 84% respectively in chronic cervicitis, CIN I, CIN II-III and cervical cancer tissues. The quantities of HPV 16 E6 gene and the expressions of survivin tended to increase along with the tumor progression (P < 0.05). The quantities of HPV16 E6 gene and the expressions of survivin of CIN I, II-III or cervical cancer were significantly higher than that of chronic cervicitis or CIN I (P < 0.01). Positive rank correlation between the quantities of HPV16 E6 gene and the expression of survivin was observed in cervical carcinoma (gamma(s) = 0.62, P < 0.05). CONCLUSIONS: The quantities of HPV16 E6 gene appear to be associated with an increased risk of developing cervical cancer. Survivin overexpression might play an important role in the process of cervical carcinoma.

Cloning and characterization of a proliferation-associated cytokine-inducible protein, CIP29.

We identified a novel erythropoietin (Epo)-induced protein (CIP29) in lysates of human UT-7/Epo leukemia cells using two-dimensional gel analysis and cloned its full-length cDNA. CIP29 contains 210 amino acids with a predicted MW of 24 kDa, and has a N-terminal SAP DNA-binding motif. CIP29 expression was higher in cancer and fetal tissues than in normal adult tissues. CIP29 mRNA expression is cytokine regulated in hematopoietic cells, being up-regulated by Epo in UT7/Epo cells, and by thrombopoietin (Tpo), FLT3 ligand (FL) and stem cell factor (SCF) in primary human CD34(+) cells. Up-regulation of CIP29 in UT7/Epo cells by Epo was associated with cell cycle progression but not with antiapoptosis. Epo withdrawal reduced CIP29 expression concomitant with cell cycle arrest. Overexpression of CIP29-GFP in HEK293 cells enhances cell cycle progression. CIP29 appears to be a new cytokine regulated protein involved in normal and cancer cell proliferation.