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Objective: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder in children. The epidemiology, clinical features and outcomes of SCN in Chinese children were reviewed.Methodology: A retrospective analysis of case records was undertaken for 18 children with SCN managed during a 12-year period in a university teaching hospital in Hong Kong.Results: The median (range) age of the patients at initial presentation was 6.5 months (4 days-19 months). The initial and lowest median absolute neutrophil counts (ANC) were 0.29 x 109 /L and 0.06 x 109 /L, respectively. Patients with congenital SCN had significantly fewer neutrophils in peripheral blood at diagnosis. Only five subjects received granulocyte colony-stimulating factor (G-CSF) treatment. All children were free from serious infection on follow up for 51 months. Only one child suffered from long-term infection-related morbidity. One patient with chronic neutropenia was subsequently shown to have common variable immunodeficiency.Conclusions: Most children with SCN in our series had favourable clinical outcomes. Our results support the recommendation that G-CSF should be used only in those with recurrent or severe infections. [ABSTRACT FROM AUTHOR]

Background: IKZF1 deletion (IKZF1 del ) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1 del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined., Methods: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1 del patients were further divided based on chemotherapy intensity for outcome assessments., Results: The BCP-ALL pediatric patients with IKZF1 del in south China showed poorer early response. Notably, the DFS and OS for IKZF1 del patients were markedly lower than IKZF1 wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1 del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1 del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026)., Conclusions: Pediatric BCP-ALL patients with IKZF1 del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1 del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1 del subset, particularly in IKZF del patients with BCR::ABL positive., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notably BCR::ABL1 + rather than KMT2A-rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL., (© 2023. The Author(s).)

Background: Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology., Objective: We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study., Search Strategy: We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to "pediatric," "cancer," and "TCM.", Inclusion Criteria: We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment., Data Extraction and Analysis: The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms., Results: The 54 studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as "moderate." In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49-4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13-0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08-0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection., Conclusion: There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Objective: Anticancer treatment may be associated with damage to the reproductive organs and risk of infertility in children with cancer. The collectivist cultural norms of Asian societies may lead Chinese parents to have unique concerns regarding infertility. This qualitative study explored the perceptions of infertility risk and parenthood among parents of childhood cancer survivors in Hong Kong. Methods: Thirteen parents were recruited via a snowball sampling approach from a nongovernmental organization in Hong Kong, representing nine survivors of childhood cancer (leukemia n  = 5, solid tumors n  = 4). The in-depth semistructured interviews were audiotaped and transcribed verbatim. A thematic analysis was performed using ATLAS.ti 8. Results: Parents mostly perceived their children's fertility status as a distant concern ( n  = 11, 85%) but emphasized the need for timely information from clinicians when their children reach young adulthood ( n  = 8, 62%). They reported receiving inconsistent fertility information from different oncology practitioners ( n  = 9, 69%). A few parents acknowledged that under the influence of the Chinese culture, their children, especially sons, have an important duty to continue the family lineage. However, even if the cancer treatment were associated with infertility risk, almost all parents ( n  = 12, 92%) stated that it would still not affect their willingness to let their child undergo treatment because survival and cure were still their highest priority. Conclusion: Our findings suggest the need to proactively provide fertility information to parents both during active treatment and when survivors reach reproductive age. Future studies should evaluate the benefits of developing culturally relevant decision-making aids to address parents' informational needs regarding fertility issues.

Purpose: This study explored the pattern of complementary or alternative medicine (CAM) use among Chinese survivors of childhood cancer and identified potential drug-CAM interactions and factors predicting CAM use., Methods: This cross-sectional study recruited 393 survivors of childhood cancer (male, 57.8%; mean age, 17.7 [SD = 7.3] years; mean years post-treatment, 8.8 [SD = 5.0]) from a public hospital in Hong Kong. Participants reported CAM and over-the-counter medications that they used in the past year. Prescription drug data were extracted from pharmacy dispensing records. Potential interactions between concurrent CAM and chronic medications were identified from well-established CAM-drug/herb-drug interaction databases. A multivariate logistic regression was performed to analyze associations of socio-demographic and clinical factors with CAM use., Results: Half (n = 205/393, 52.2%) of the participants reported the use of CAM. The most popular CAMs were traditional Chinese medicine (n = 127/205, 62.0%) and natural products (n = 114/205, 55.3%). Among the 69 survivors (33.7%) concurrently using CAM and chronic medications, one-third (n = 21/69, 30.4%) were at risk of drug-CAM interactions that are of moderate significance. Adult survivors were more likely to use CAM than pediatric survivors (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.31-4.41). Brain tumor survivors were more likely than other solid tumor survivors to use non-oral therapies (OR, 2.70; 95% CI, 1.01-7.72)., Conclusions: The prevalence of CAM use among Chinese survivors of childhood cancer was high. A minority of survivors had a risk of clinically significant CAM-drug interactions. Future studies should focus on survivors' behavior and motivations for CAM use., Implications for Cancer Survivors: As the concurrent use of CAM and chronic medications might result in interactions, healthcare providers should proactively identify such interactions and develop referral pathways to promote evidence-based integrative therapies for survivors., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Inter-individual variance in 6-mercaptopurine (6-MP) dose intensity is common in patients with acute lymphoblastic leukemia (ALL). We aimed to evaluate the association of common variants of ABCC4 , ITPA , NUDT15 , and TPMT with 6-MP dose intensity and toxicity in pediatric ALL patients. In this cohort, 13.8% of patients were intolerant to 6-MP with actual dosage less than 50% of scheduled dose. Twenty percent of patients were found to be heterozygous or homozygous mutated with NUDT15 . NUDT15 c.415C > T and the genotype-predicted NUDT15 activity were significantly associated with 6-MP intolerance. TPMT *3C variants were not common in this cohort (2.8%). NUDT15 polymorphisms and genotype predicted NUDT15 activity were significantly associated with 6-MP dose intensity and leukopenia episodes. Combination of ABCC4 and ITPA variants ( ABCC4 c.912G > T and ITPA c.94C > A) also showed significant positive association with 6-MP intolerance in Chinese children with ALL. Further study on pharmacogenetic screening for ALL patients to avoid 6-MP induced toxicity is recommended.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1973628.

Background: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia., Methods: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m 2 ) plus oral dexamethasone (6 mg/m 2 per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706., Findings: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060)., Interpretation: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia., Funding: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests C-HP is on the scientific advisory board of Adaptive Biotechnology and the Data Monitoring Committee of Novartis; and has received honorariums from Amgen and Erytech. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: For survivors of childhood cancer, awareness of personal health risks is a critical component of long-term health management., Objective: To evaluate the awareness of the diagnosis, treatment and risk of late effects among survivors of childhood cancer in Hong Kong., Methods: Between June 2019 and March 2020, this cross-sectional study recruited 155 adult survivors (mean age = 26.9, standard deviation [SD] = 6.4 years) and 45 parents of paediatric survivors (mean age = 11.1, SD = 3.6 years) from a long-term follow-up clinic. At >10 years post-treatment (mean = 13.4, SD = 7.6 years), they completed a structured questionnaire to report their cancer-specific knowledge. Multiple linear regression analysis was conducted to identify clinical, socioeconomic and behavioural factors associated with poor awareness., Results: The majority of participants accurately recalled their diagnoses (73.5%) and major treatment modalities (chemotherapy 92.4%, radiation 82.9% and surgery 88.2%). However, less than half (45%) of the participants recognized more than 25% of the total late effects for which they were at risk. The highest levels of awareness were reported for endocrine problems (49%), neurocognitive impairment (44%) and secondary cancers (43%), and the lowest for peripheral neuropathy (21%) and vision problems (23%). Compared with survivors of haematological malignancies, those of central nervous system (CNS) tumours (standardized estimate [B] = -9.33, 95% confidence interval [95% CI]: -13.41 to -5.26) and non-CNS solid tumours (B = -8.47, 95% CI: -12.39 to -4.94) had less knowledge about their diagnosis. Retaining medical records (P < .0001) and better medical information-seeking habits (P = .048) were associated with better awareness., Conclusions: Survivors of childhood cancer in Hong Kong have deficient awareness of their personal health risks. They may benefit from the provision of a survivorship care plan and personalized education regarding treatment-related late effects., Patient Contribution: Patients contributed in designing the study tools. Results were presented at a non-governmental organization., (© 2021 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Objectives: Parents of children diagnosed with critical illnesses face multiple challenges during their caregiving experience. However, relevant studies have been limited in the Chinese context. Guided by the stress and coping model, we conducted a qualitative study to identify the stressors, coping strategies, and adjustment experiences of Hong Kong parents of children with cancer or hematological disorders., Methods: We recruited 15 parents of children with cancer or hematological disorders requiring bone marrow transplantation and were currently >2 years post-treatment. They participated in a 30-min semi-structured interview. Thematic analysis was performed using the grounded theory approach., Results: The stressors reported by parents included a high caregiving burden during their children's diagnosis and treatment stages. The fear of recurrence, the need for information, and concerns about late effects were also common among the parents during their children's transition/survivorship stage. To cope with these stressors, the parents commonly used problem-focused (e.g., seeking help from professionals and support groups) and emotion-focused (e.g., behavioral distractions, venting, and crying) strategies. Despite these stressors, parents reported positive changes through the caregiving experience, such as improved family relationships, developing health-protective habits, and the reprioritization of different aspects of life., Conclusions: Parents encounter different stressors during the cancer care continuum. Using different coping strategies, parents experience positive changes amidst caregiving. Future studies should explore culturally relevant adaptive coping strategies to enhance parents' psychosocial adjustment.

Purpose: Survivors of childhood cancer often experience treatment-related chronic health conditions. Given its vast population, China shares a large proportion of the global childhood cancer burden. Yet, screening and treatment of late effects in survivors of childhood cancer remain underaddressed in most regions of China. This study aimed to identify high-priority late effects for harmonizing screening guidelines within the Chinese Children's Cancer Group (CCCG), as well as barriers and enablers of the implementation of surveillance recommendations in local practice., Methods: To establish clinical consensus, 12 expert panelists who represent major institutions within the CCCG completed a Delphi survey and participated in a focus group discussion. The survey solicited ratings of the prevalence, severity, and priority for screening of 45 late effects. Major themes identified from the focus group were analyzed using thematic analysis., Results: The Delphi survey identified eight high-priority late effects for harmonization within CCCG: osteonecrosis, osteoporosis, left ventricular dysfunction, secondary brain tumors, treatment-related myeloid leukemia, gonadal dysfunction, growth hormone deficiency, and neurocognitive deficits. The common barriers to implementing survivorship programs include lack of support and resources for clinicians to provide follow-up care. Patients were also concerned about privacy issues and lacked awareness of late effects. Many institutions also lacked rehabilitation expertise and referral pathways., Conclusion: By identifying obstacles related to the professional setting, patient behavior, and organization of care, our study identified resources and a framework for establishing collaborative strategies to facilitate follow-up care of childhood cancer survivors in China.

Objectives: Children with cancer are exposed to repeated painful and invasive procedures. This study examines Chinese parents' stress and perception toward their children's procedural pain control., Methods: We recruited 265 parents of children (aged <18 years) diagnosed with hematological cancer (74.7%) and solid tumors (25.3%) from two major public hospitals. Parents used a scale (0-10) to rate perceived pain experienced by their child when undergoing lumbar puncture (LP), bone marrow aspirate, or/and biopsy. They reported their stress level and attitudes toward analgesics using the adapted Pain Flexibility Scale for Parents and Parental Medication Attitude Questionnaire. General linear modeling was used to identify factors associated with perception outcomes., Results: Parents (72.8% mothers, age 36.5 [6.8] years) expressed that they were worried (31.7%) and had difficulty with concentration (57.7%) when the child was in pain. Among parents whose children had undergone LP (n = 207), 39.1% perceived that their child still experienced severe pain (pain score >7) even with existing pain control measures. Parents reported concerns over side effects of analgesics (69.4%) and addiction (35.1%). Half of the parents (47.2%) perceived that analgesics should only be reserved for severe pain. Parents who were older (estimate = 2.07, SE = 0.87; P = 0.0054) and had lower education attainment (estimate = -3.38, SE = 1.09; P = 0.0021) had a more negative attitude toward analgesics use. Higher parental distress was associated with avoidance of analgesics use (r s  = 0.17, P = 0.0052)., Conclusion: Our findings suggested that subgroups of Chinese parents demonstrated distress with their child's pain and harbored misconceptions over analgesics use. Future work includes devising targeted psychoeducation interventions for these parents., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Septicemia is an important cause of treatment-related mortality and treatment failure in pediatric acute lymphoblastic leukemia (ALL) in developing countries. A multicenter CCCG-ALL-2015 study was conducted in China and factors associated with septicemia and mortality were studied., Methods: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included. Patients with documented septicemia were identified from the Data Center and additional data were collected., Results: A total of 4080 patients were recruited in the study and 527 patients with septicemia were identified (12.9%, 95% CI 11.9%-13.9%). The intermediate risk (IR)/high risk (HR) group had significantly higher incidence of septicemia as compared with low risk (LR) group, 17.1% vs 9.1% (OR 2.07, 95% CI 1.71-2.49, P < .001). Induction phase was the period with majority of septicemia episodes happened, 66.8% in LR and 56.1% in IR/HR groups. Gram-positive bacteria accounted for 54.1%, gram-negative bacteria 44.5%, and fungus 1.4% of positive cultures. Multidrug-resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.4% (95% CI 1.9%-4.9%). Multiple logistic regression identified female gender, comorbid complications, and fungal infection as risk factors associated with mortality. Gram-negative septicemia was associated with higher mortality, 4.9% vs 1.4% (OR 0.28, 95% CI 0.09-0.88, P = .02). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%., Conclusion: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to the reports of western countries. The septicemia-related mortality rate was low. There was marked variation in the incidence of septicemia among the centers., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To investigate the effect of long-term exposure of nitrogen dioxide on the incidence of hypertension. Methods: From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow-up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self-report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO 2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO 2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO 2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results: The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m(2). During an average follow-up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m(3). After adjusting for age, sex, BMI, family history of hypertension, socio-economic information, and lifestyle, the hazard ratio ( HR ) of incident hypertension with a 10 μg/m(3) increase of NO 2 was 1.21 (95 %CI : 1.18-1.25). Compared with residents aged 60 years and over ( HR =1.19, 95 %CI : 1.14-1.26), former and current smoking ( HR =1.20, 95 %CI : 1.14-1.25), and high-frequency fruit consumption ( HR =1.17, 95 %CI : 1.13-1.21), residents younger than 60 years ( HR =1.28, 95 %CI : 1.25-1.32), non-smoker ( HR =1.23, 95 %CI : 1.19-1.27), and low-frequency fruit consumption ( HR =1.27, 95 %CI : 1.20-1.35) had stronger interaction effect with NO 2 (all P values for interaction < 0.05). Conclusion: NO 2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low-frequency fruit consumption.

Objectives: Before 2003, most children with acute lymphoblastic leukaemia (ALL) abandoned treatment, with only approximately 30% treated in China. With the development of national insurance for underprivileged patients, we assessed the current frequency and causes of treatment abandonment among patients with ALL who were enrolled in the Chinese Children's Cancer Group ALL protocol between 2015 and 2016., Methods: Demographic, clinical and laboratory data on patients who abandoned treatment, as well as economic and sociocultural data of their families were collected and analysed. General health-related statistics were retrieved from publicly accessible databanks maintained by the Chinese government., Results: At a median follow-up of 119 weeks, 83 (3.1%, 95% CI 2.5% to 3.8%) of the 2641 patients abandoned treatment. Factors independently associated with abandonment included standard/high-risk ALL (OR 2.62, 95% CI 1.43 to 4.77), presence of minimal residual disease at the end of remission induction (OR 3.57, 95% CI 1.90 to 6.74) and low-income economic region (OR 3.7, 95% CI 1.89 to 7.05). According to the family members, economic constraints (50.6%, p=0.0001) were the main reason for treatment abandonment, followed by the belief of incurability, severe side effects and concern over late complications., Conclusions: The rate of ALL treatment abandonment has been greatly reduced in China. Standard/high-risk ALL, residence in a low-income region and economic difficulties were associated with treatment abandonment., Clinical Trial Registration Number: ChiCTR-IPR-14005706, pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To analyze the mortality and years of life lost (YLL) trends of cervical cancer in Tianjin, and provide references for the research and prevention programs of cervical cancer. Methods: Mortality rate, standard mortality rate, cumulative rate (0-74 years-old) and truncated rate (35-64 years-old) of cervical cancer from 1999 to 2015 were calculated. The annual percentage change of the mortality rate and YLL rate were analyzed by using Joinpoint regression analysis, and the trend in different age-groups were analyzed. Results: From 1999 to 2015, 1 741 cases died of cervical cancer in Tianjin, the average crude mortality rate was 2.15/100 000. The average age-standardized rate of (ASR) China and ASR world were 1.47/100 000 and 1.50/100 000 respectively. The average YLL was 3 347.97 person-years. Deaths occurred in those aged 0-34 years, 35-64 years and 65 years and over accounted for 3.10 % , 57.84 % and 39.06 % of the total, respectively. The mortality rate of cervical cancer in urban area was higher than that in rural area, with a ratio of 1.37∶1 between urban area and rural area. The age-specific mortality rate of cervical cancer during 1999-2015 increased with age. Two peaks of mortality rate were observed in those aged 50 years and aged 75 years, during 2014-2015. From 1999 to 2011, the mortality rate of cervical cancer was stable (APC=-0.2 % , P =0.80), but there was a rapid increase from 2011 to 2015 (APC=21.6 % , P <0.01). But group aged 20-49 years, it showed an upward trend from 1999 to 2015 (APC=6.9 % , P <0.01). For group aged 50-69 years, it showed a downward trend from 1999 to 2007 (APC=-9.2 % , P <0.01), and an upward trend from 2007 to 2015 (APC=14.5 % , P <0.01). For group aged 70 years and over, it showed a downward trend from 1999 to 2009 (APC=-10.2 % , P <0.01), but the difference in the mortality were not significant from 2009 to 2015 (APC=7.8 % , P =0.10). Since 2008, the YLL rate of cervical cancer in group aged 50-70 years had exceeded that in group aged >70 years and the gap gradually widened. Conclusions: There had been a rapid increase trend of cervical cancer mortality since 2011 in Tianjin. Women aged 50-70 years were the main group of life loss.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)-ALL 2008 was a prospective clinical trial designed to improve treatment outcome of childhood ALL through the first nation-wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical-biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25%-50% dose reduction during intensification phases in the SR group. Patients in high risk (HR) group received a more intensive maintenance treatment. Minimal residual disease (MRD) monitoring with treatment adjustment was performed in two hospitals (the MRD group). Complete remission (CR) was achieved in 2100 patients (94.1%). At five years, the estimate for overall survival (OS) and event-free survival (EFS) of the whole group was 85.3% and 79.9%, respectively. The cumulative incidence of relapse (CIR) was 15.3% at five years. The OS, EFS and CIR for the SR group were 91.5%, 87.9%, and 9.7%, respectively. The outcome of the MRD group is better than the non-MRD group (5y-EFS: 82.4% vs 78.3%, P = .038; 5y-CIR: 10.7% vs 18.0%, P < .001). Our results demonstrated that the large-scale multicenter trial for pediatric ALL was feasible in China. Dose reduction in the SR group could achieve high EFS. MRD-based risk stratification might improve the treatment outcome for childhood ALL., (© 2018 Wiley Periodicals, Inc.)

A fetus of Chinese descent presented with ultrasound features of anemia at 20 weeks' gestation. Father had low a mean corpuscular volume (MCV) level. Multiplex gap-polymerase chain reaction (gap-PCR) excluded common α-thalassemia (α-thal) deletions and mutations and PCR sequencing of the α1- and α2-globin genes were negative. The fetus had a normal karyotype. Array comparative genomic hybridization (aCGH) showed a single copy loss of 189.87 kb in chromosome 11p15.4, involving the whole β-globin gene cluster, inherited from the father. Multiplex ligation-dependent probe amplification (MLPA) confirmed the deletion included the ε-globin gene, confirming the diagnosis of heterozygous (εγδβ) 0 -thalassemia [(εγδβ) 0 -thal], also inherited from the father. The fetus had a worsening anemic condition in utero and required a transfusion at 26 weeks' gestation, raising the hemoglobin (Hb) level from 5.3 to 12.6g/dL. A cesarean-section was subsequently performed at 32 weeks' gestation because of reduced fetal movements, and a 1650g baby girl with good Apgar scores was delivered. Hemoglobin at birth was 12.8g/dL, gradually dropping to 6.8 g/dL, requiring three neonatal transfusions. Her condition gradually stabilized after 2 months with Hb stable at 8.0 g/dL. Family screening by MLPA showed that the paternal grandmother carried the same deletion. The deletion in this case is distinct and is the reported first case. The deletion transmitted across three successive generations with great phenotypic variation. The final adult phenotype of (εγδβ) 0 -thal is usually mild, therefore, with accurate prenatal diagnosis this condition is salvageable by in utero and early neonatal transfusions, preventing adverse pregnancy and neonatal outcomes.

Thalassaemia is the most common monogenic disorder worldwide. It is common in areas with prevalent malaria as thalassaemic red cells provide immunity against the parasite. The incidence of thalassaemia carriers is high in regions such as Mediterranean, Middle East, Indian subcontinent, Southeast Asia and South China. In the past few decades, migrants from the thalassaemia prevalent countries to non-prevalent countries, mainly North America and Central and North Europe, are rapidly increasing in number. The non-prevalent countries may not have established pre-natal screening system for thalassaemia. The genetic subtypes among the different ethnic groups vary; this may pose challenges in prenatal diagnosis. Genetic counselling on the postnatal course of thalassaemia may be affected by the genotype-phenotype correlation and coinheritance of other genetic diseases. New treatment methods improve the survival of patient with thalassaemia major, but some late complications that occur with longer survival have been recently discovered., (Copyright © 2016. Published by Elsevier Ltd.)

The management of central nervous system tumors in children below the age of 3 years represents a special challenge to pediatric oncologists with distinctive epidemiology, treatment considerations, and prognosis. Population-based epidemiological data on this particular patient group is lacking in Chinese. We reviewed the population-based pediatric tumor registry in Hong Kong between 1999 and 2011. Eighty-one children with primary central nervous system tumors from 0 to 3 years of age were identified (annual incidence: 4.16 cases per 100,000). Forty-one (50.6%) were male and the mean duration of follow-up was 94 months (±8.1). Primary tumors were infratentorial in 43 (53.1%). The tumor types in decreasing frequency were astrocytoma (n=17), medulloblastoma (n=16), ependymoma (n=13), choroid plexus tumor (n=7), primitive neuroectodermal tumor (n=7), atypical teratoid rhabdoid tumor (n=6), germ cell tumor (GCT, n=5), craniopharyngioma (n=4), and ganglioglioma (n=3). Three patients presented antenatally. Treatment included surgery in 82.7%, chemotherapy in 50.6%, and radiotherapy in 25.9%. There were 29 deaths (35.8%) and 19 relapses (23.5%) during the review period with the 1-year overall survival (OS), 5-year OS, 1-year event-free survival (EFS), and 5-year EFS being 79.4% (±4.6), 63.5% (±5.9), 68.9% (±5.3), and 52.5% (±5.9), respectively. Significantly better OS and EFS were observed in patients who received gross total resection, but those with high-grade tumors, antenatal diagnosis, or atypical teratoid rhabdoid tumor/primitive neuroectodermal tumor had worse outcome. Survival did not differ with age. Comparison with statistics from other studies revealed higher rates of embryonal tumor, GCT, and craniopharyngioma in Hong Kong Chinese. Disease outcome appeared to be better in our cohort comparing to previous reports probably due to the higher proportion of GCT locally.

Inherited metabolic diseases (IMDs) are a large group of rare genetic diseases. The spectrum and incidences of IMDs differ among populations, which has been well characterised in Caucasians but much less so in Chinese. In a setting of a University Hospital Metabolic Clinic in Hong Kong, over 100 patients with IMDs have been seen during a period of 13 years (from 1997 to 2010). The data were used to define the spectrum of diseases in the Southern Chinese population. Comparison with other populations revealed a unique spectrum of common IMDs. Furthermore, the incidence of the common IMDs was estimated by using population carrier frequencies of known recurrent mutations. Locally common diseases (their estimated incidence) include (1) glutaric aciduria type 1 (∼1/60,000), (2) multiple carboxylase deficiency (∼1/60,000), (3) primary carnitine deficiency (∼1/60,000), (4) carnitine-acylcarnitine translocase deficiency (∼1/60,000), (5) glutaric aciduria type 2 (∼1/22,500), (6) citrin deficiency (∼1/17,000), (7) tetrahydrobiopterin-deficient hyperphenylalaninaemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency (∼1/60,000), (8) glycogen storage disease type 1 (∼1/150,000). In addition, ornithine carbamoyltransferase deficiency and X-linked adrenoleukodystrophy are common X-linked diseases. Findings of the disease spectrum and treatment outcome are summarised here which may be useful for clinical practice. In addition, data will also be useful for policy makers in planning of newborn screening programs and resource allocation.

Background: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales are commonly used to assess health-related quality of life of healthy children and pediatric patients. Validation of the Generic Core Scales among Chinese pediatric cancer patients has not been reported in the literature. The scales can serve to measure different quality-of-life domains that are not captured by the PedsQL Cancer Module., Objective: Psychometric properties of the Chinese version of the PedsQL 4.0 among pediatric cancer patients and their caretakers were examined., Methods: The Generic Core Scales were administered to 335 pairs of pediatric cancer patients (aged 8-18 years) and their caretakers in Hong Kong., Results: A 5-factor structure (physical, emotional, social, school-related cognitive function, and missed school) was identified in the patient and proxy versions of the scales using confirmatory factor analysis. Both versions of the total scale reported Cronbach α's of .90 or greater, with almost all subscales reporting α's of .70 or greater. Test-retest reliability at 2 weeks was acceptable (intraclass correlations ≥0.60) for a majority of subscales. Agreement between patients' and caretakers' ratings was medium., Conclusions: The scales demonstrated acceptable psychometric properties and construct validity., Implications for Practice: This study validated the Chinese version of the Generic Core Scales among pediatric cancer patients and their caretakers, which supports the future use of the scales in clinical settings. The Generic Core Scales can also be supplementary to the PedsQL Cancer Module for measuring multiple domains of quality of life in cancer population.

Background: Childhood cancer survivors were at risk of development of second malignant neoplasms. The aim of this study is to evaluate the incidence, risk factors and outcome of second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China., Methods: We performed a retrospective review of patients with childhood cancer treated in Children's Cancer Centre in Prince of Wales Hospital, Hong Kong, China between May 1984 and June 2009. Case records of patients who developed second malignant neoplasms were reviewed., Results: Totally 1374 new cases aged less than 21-year old were treated in our centre in this 25-year study period. Twelve cases developed second malignant neoplasms with 10-year and 20-year cumulative incidence of 1.3% (95% confidence interval 0.3% - 2.3%) and 2.9% (95% confidence interval 1.1% - 4.7%) respectively. Another 4 cases were referred to us from other centres for the management of second malignant neoplasms. In this cohort of 16 children with second malignant neoplasms, the most frequent second malignant neoplasms were acute leukemia or myelodysplastic syndrome (n = 6) and central nervous system tumor (n = 4). Median interval between diagnosis of primary and second malignant neoplasms was 7.4 years (range 2.1 - 13.3 years). Eight patients developed second solid tumor within the previous irradiated field. Radiotherapy significantly increased the risk of development of second solid tumor in patients with acute lymphoblastic leukemia (P = 0.027). Seven out of 16 patients who developed second malignant neoplasms had a family history of cancer among the first or second-degree relatives. Nine patients died of progression of second malignant neoplasms, mainly resulted from second central nervous system tumor and osteosarcoma., Conclusions: Cumulative incidence of second cancer in our centre was comparable to western countries. Radiotherapy was associated with second solid tumour among patients with acute lymphoblastic leukemia. Patients who developed second brain tumor and osteosarcoma had a poor outcome.

With the use of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT), the prognosis of childhood acute myeloid leukemia (AML) improved over the last 2 decades. Survival data of Chinese pediatric patients were seldom reported. The authors adopted modified UK Medical Research Council (MRC) AML protocols for treatment of childhood AML since 1994. From 1994 to 2008, the outcomes of Chinese AML patients were studied. Sixty-eight patients were studied. The median age at diagnosis was 9.9 years. Twenty-five patients (36.8%) had favorable cytogenetic karyotypes, including t(15;17), t(8;21) and inv(16). Complete remission (CR) rate was 91.2%. The relapse rate was 29.4%. For non-M3 patients, the 5-year overall survival (pOS) was 64% ± 7% and event-free survival (pEFS) was 53% ± 7%. For those non-good-risk patients who achieved CR, there were no significant differences in outcomes between patients who received HSCT in CR1 and those received chemotherapy alone (5-year pOS 80% ± 13% and 69% ± 9%, P = .52), 5-year pEFS 69% ± 15% and 55% ± 10%, P = .40). The pOS of the 20 relapsed patients was 29% ± 11%. Sixteen patients with t(8;21) and inv(16) had similar outcome with those without favorable cytogenetics (pOS 66% ± 12% versus 65% ± 7%, P = .39; pEFS 60% ± 11% versus 54% ± 8%, P = .45). Patients who achieved CR after 2 or more courses of chemotherapy and presenting white blood cell count (WBC) ≥ 100 × 10(9)/L had poorer outcome (pOS 40% versus 80%P < .01; 43% versus 70%, P = .02, respectively). Intensified chemotherapy improved outcome of Chinese AML children. CR after first course of chemotherapy and WBC at diagnosis were important prognostic factors.

Beta thalassaemia major is a common hereditary haematological disease in southern Chinese. Advances in transfusion and iron chelation improve survival but haematopoietic stem cell transplantation (HSCT) is still the only curative treatment. Due to repeated blood transfusion and iron overload, thalassaemia patients undergoing HSCT are at a higher risk of graft rejection and transplant-related mortality. The prognostic factors identified to be affecting transplant outcome include hepatomegaly, hepatic fibrosis, and compliance to chelation therapy. Patients can be classified into three classes and conditioning regimens are modified according to the risk. Early stage patients have 85 to 90% chance of disease-free survival, whereas advance stage only has 60% disease-free survival. Mixed chimerism is common after HSCT but majority have satisfactory erythropoiesis without need for further transfusion. Sibling cord blood and bone marrow transplantation has similar outcome. Recently alternative donor transplant has been performed in patients without human leukocyte antigen (HLA)-identical siblings. The result of unrelated-donor bone marrow transplantation is in general inferior but extended HLA matching may improve outcome. The use of unrelated cord blood transplant from a single-centre study showed promising result. The survivors require iron depletion to remove excessive iron store and some may require hormonal replacement therapy. Most of the patients have good quality of life after successful HSCT.

Background: To evaluate the prevalence of chronic kidney disease (CKD) in Chinese HIV-infected population., Methods: This was a cross-sectional point prevalence study. All Chinese HIV-infected patients who were followed up in a tertiary referral center in Hong Kong were recruited. Spot urine was saved for each patient to calculate urine protein-to-creatinine ratio (urine P/Cr). Those with urine P/Cr > 0.3 would have 24-h urine collection to determine the exact amount of proteinuria. Glomerular filtration rate (GFR) was estimated using MDRD formula. CKD was defined as GFR <60 ml/min/1.73 m2 and/or urine P/Cr > 0.3. Baseline demographic and clinical data were extracted from patients' records., Results: In total 322 patients were recruited. The mean age was 45.2 +/- 11.7 years. The duration of follow up was 6.0 +/- 4.0 years. There were 264 male and 58 female patients. The prevalence of hypertension, diabetes mellitus and CKD were 7.4%, 10.6% and 16.8%, respectively. Eighteen patients (5.6%) had GFR < 60 ml/min/1.73 m2 while 44 patients (13.7%) had spot urine P/Cr > 0.3. Among those with urine P/Cr > 0.3, 38 patients had 24-h urine collection. Using univariate analysis, CKD was found to be significantly (P < 0.05) associated with age, hypertension, diabetes, use of indinavir, lower CD4 count and peak viral load. Multivariate logistic regression revealed older age (P < 0.001), lower CD4 count (P = 0.02) and use of indinavir therapy (P = 0.04) were associated with development of CKD., Conclusion: CKD is prevalent in Chinese HIV-infected patients. Patients with CKD were more likely to be older, associated with use of indinavir and CD4 nadir less than 100 cells/mul.

This paper reports a statistical study on the sequence of strokes of 61 commonly encountered Chinese radicals and characters written by 372 invited subjects. The distribution of different writing sequence of these Chinese radicals and characters was examined. Comparison of the sequence of strokes executed by the subjects with the standard rule of writing these Chinese radicals and characters revealed that around 60% of the subjects wrote in the correct sequence. Pair comparison of sequences of strokes in Chinese handwriting among the 372 subjects was also performed. The results demonstrated that no two individuals wrote all the 61 radicals and characters with the same sequence of strokes. The findings indicate that, despite some basic rules governing the writing sequence of Chinese characters, writers tend to develop their own habits. The findings also support the hypothesis that the handwriting of experienced writers is individual.

We describe a case of coexisting BCR-ABL negative myeloproliferative disorder and precursor T-cell lymphoblastic lymphoma associated with t(8;13) involving FGFR1 at 8p11 in a 14-year-old boy who presented with generalized lymphadenopathy and an abdominal mass. JAK2 mutation and FIP1L1-PDGFRalpha were not detected. RT-PCR revealed the ZNF198-FGFR1 fusion transcript in both the bone marrow (BM) and lymph node (LN) of the patient at diagnosis. Of interest, reciprocal FGFR1-ZNF198 fusion transcript was demonstrated in the BM but not LN. Also differential clonal TcRgamma gene rearrangements in the BM and LN samples were observed. These findings provide novel insights into the genetic pathogenesis.

Osteoporosis and osteopenia affect up to half of patients with thalassaemia major (TM). We investigate the effects of acquired factors and BMT on bone mineral density (BMD) in these patients. In all, 53 patients on regular transfusion (BT group) and 33 patients at 5.7+/-1.9 years post transplant (BMT group) were recruited. BMD was measured by dual energy X-ray absorptiometry. Serum concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta-crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z-score <-2.5) at spine and hip were noted in 62 and 35% of BT group. Serum osteocalcin (beta=-0.463; P=0.006) was predictive of spine BMD, whereas age (beta=-0.843; P=0.007) and urine DPD (beta=-0.439; P=0.037) were associated with hip BMD in BT group. Among BMT patients, post transplant duration (beta=0.450; P=0.009) and serum bone-specific ALP (beta=-0.495; P=0.013) were associated with spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs 35%; P=0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4 (72.7) microg and 68.9 (40.3) microg/l, respectively (P=0.037). In conclusion, severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD deficit in these patients., (Bone Marrow Transplantation (2005) 36, 331-336.)

To evaluate factors affecting outcome of sibling umbilical cord blood transplantation in Chinese children with thalassemia. The authors conducted a retrospective review of all patients undergoing such transplants in a single institution. Nine children with thalassemia major were diagnosed at a median age of 12 months. They received irregular blood transfusions and suboptimal iron chelation therapy before transplant. Sibling cord blood transplant was performed at a median of 5.5 years (range 3.5-10 years). Six donors were HLA-identical; three were one- to three-antigen mismatched. The mean number of nucleated cells infused was 6.6 x 10(7)/kg (range 3.4-12.7); the mean number of CD34+ cells infused was 3.8 x 10(5)kg (range 0.6-11.7). Seven patients had engraftment of donor cells. The median number of days to achieve a neutrophil count of > 0.5 x 10(9)/L was 19 days (range 10-25); the median number of days to achieve a platelet count of > 20 x 10(9)/L was 33 days (range 19-63). Of the six patients who received HLA-identical transplants, one developed grade 2 and two developed grade 1 acute graft-versus-host disease. Two of the three patients receiving mismatched cord blood did not achieve engraftment, and the other one engrafted but developed grade 4 acute graft-versus-host disease. Two patients subsequently developed secondary graft rejection and had autologous marrow regeneration before day 60 posttransplantation. With a median follow-up of 49 months (range 38-64), eight patients survived but only four were transfusion-independent. Umbilical cord blood transplant appears to have a higher chance of nonengraftment and secondary rejection. A more intensive immunosuppressive conditioning regimen may be required.

Isolated sulfite oxidase deficiency is a rare autosomal recessive disease, characterized by severe neurological abnormalities, seizures, mental retardation, and dislocation of the ocular lenses, that often leads to death in infancy. There is a special demand for prenatal diagnosis, since no effective treatment is available for isolated sulfite oxidase deficiency. Until now, the cDNA sequence of the sulfite oxidase (SUOX) gene has been available, but the genomic sequence of the SUOX gene has not been published. In this study, we have performed a DNA-based diagnosis of isolated sulfite oxidase deficiency in a Chinese patient. To do so, we designed oligonucleotide primers for amplification of the predicted exons and intron-exon boundaries of the SUOX gene obtained from the completed draft version of the human genome. Using overlapping PCR products, we confirmed the flanking intronic sequences of the coding exons and that the entire 466-residue mature peptide is encoded by the last exon of the gene. We then performed mutation detection using denaturing high-performance liquid chromatography (DHPLC). The DHPLC chromatogram of exon 2b showed the presence of heteroduplex peaks only after mixing of the mutant DNA with the wild-type DNA, indicating the presence of a homozygous mutation. Direct DNA sequencing showed a homozygous base substitution at codon 160, changing the codon from CGG to CAG, which changes the amino acid from arginine to glutamine, i.e., R160Q. The DNA-based diagnosis of isolated sulfite oxidase deficiency will enable us to make an accurate determination of carrier status and to perform prenatal diagnosis of this disease. The availability of the genomic sequences of human genes from the completed draft human genome sequence will simplify the development of molecular genetic diagnoses of human diseases from peripheral blood DNA., ((C)2002 Elsevier Science (USA).)

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.

Teratoma is a rare tumour in children accounting for about 3% of all childhood malignancy. A case of immature mediastinal teratoma in a young Chinese girl is reported.

We report here a family of patients with coexistent hereditary spherocytosis and alpha-thalassaemia. The different clinical presentations of the family members were affected by the severity of the alpha-thalassaemia. The haemolytic effect of hereditary spherocytosis was modulated by the increased osmotic resistance of thalassaemia in the patients with both disorders. Coexistence of haemoglobin H disease and hereditary spherocytosis resulted in an asymptomatic state. In contrast, coexistence of alpha-thalassaemia trait and hereditary spherocytosis was still haemolytic. The different shapes of the osmotic curves in the family members correlated with the severity of their symptoms.

We report a case of transient myeloproliferative disorder (TMD) involving the megakaryocytic lineage in a cytogenetically normal newborn infant. Prominent megakaryocytic phagocytosis in the bone marrow was observed. This finding might suggest that TMD was due to a self-limiting malignant clone in myelopoiesis.