1.Initial clinical outcomes of the comprehensive debulking surgery for one-stage reconstruction of multiple toes macrodactyly in children
Guoqing CHEN ; Xiaofei TIAN ; Xionghui DING ; Jun XIAO ; Hai ZHU ; Ailian MEI ; Chao WEI
Chinese Journal of Plastic Surgery 2024;40(6):587-596
Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.
2.Initial clinical outcomes of the comprehensive debulking surgery for one-stage reconstruction of multiple toes macrodactyly in children
Guoqing CHEN ; Xiaofei TIAN ; Xionghui DING ; Jun XIAO ; Hai ZHU ; Ailian MEI ; Chao WEI
Chinese Journal of Plastic Surgery 2024;40(6):587-596
Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.
3.Observing the Changes of White Matter Microstructure in Moderate and Severe Obstructive Sleep Apnea-Hypopnea Syndrome via Synthetic MRI
Qing LIU ; Kun PENG ; Kaiyu WANG ; Ning ZHANG ; Ailian XIAO
Chinese Journal of Medical Imaging 2024;32(10):988-993
Purpose To study the changes of white matter microstructure in moderate and severe obstructive sleep apnea-hypopnea syndrome(OSAHS)via synthetic MRI.Materials and Methods A total of 30 patients with moderate and severe OSAHS diagnosed for the first time and 30 healthy controls were prospectively collected in General Hospital of Taiyuan Iron&Steel(Group)Co.,LTD from October 2022 to September 2023.Both groups underwent routine MRI,3D-T1 MPRAGE and synthetic MRI scans.The T1,T2 and proton density(PD)values of multiple white matter regions in the two groups were compared,and the correlation between T1,T2 and PD values in different brain regions and sleep parameters was analyzed.Results Compared with the control group,the T1 value were increased in various white matter regions,including the right cerebral peduncle,cingulate fasciculus,posterior thalamic radiation,external capsule,bilateral internal capsule,corona radiata,superior longitudinal fasciculus and superior frontal-occipital fasciculus(t/Z=-3.267-3.286,all P<0.05).The T2 value of the left inferior cerebellar peduncle was decreased(Z=2.114,P=0.035),and the T2 value of the right posterior thalamic radiation and bilateral external capsule were increased(Z=-2.410,-2.484,-2.306,all P<0.05).Furthermore,the PD value were increased in corpus callosum,left internal capsule,sagittal layer,hippocampus,right posterior thalamic radiation,cingulate fasciculus,bilateral corona radiata and superior longitudinal fasciculus(t/Z=-3.726-2.757,all P<0.05).The apnea hypopnea index of patients with moderate and severe OSAHS was positively correlated with the T1 value(r=0.387,P=0.035)and PD value(r=0.382,P=0.037)of the right cingulate bundle,and there was no correlation between the lowest oxygen saturation and the quantitative parameters in moderate and severe OSAHS(P>0.05).Conclusion Synthetic MRI can sensitively observe the changes of white matter relaxation values in moderate and severe OSAHS,and has high application value in evaluating the damage of white matter in OSAHS.
4.Efficacy of surgical treatment for 35 children with nail matrix nevi
Yan LIU ; Lin QIU ; Yuexian FU ; Xiaofei TIAN ; Xingang YUAN ; Jun XIAO ; Tianwu LI ; Xiaobo MAO ; Ailian MEI ; Yongqiang GUO ; Rong ZHOU
Chinese Journal of Dermatology 2022;55(5):430-433
Objective:To explore rational surgical treatment for childhood nail matrix nevi.Methods:A retrospective analysis was conducted on clinical data from 35 children with pathologically confirmed nail matrix nevi, who received surgical treatment in Children′s Hospital of Chongqing Medical University from September 2015 to March 2019. Different surgical approaches were adopted according to the site and width of lesions. For lesions with a width of ≤ 3 mm, the nail bed and nail matrix lesions were directly excised with 1-to-2-mm margins and sutured in 11 cases. For lesions with a width of > 3 mm, one of the following 3 surgical procedures was selected by the children′s parents: (1) shaving of nail bed and nail matrix lesions under a microscope at ×8 magnification (8 cases) ; (2) excision of lesions followed by full-thickness skin grafting on the periosteum of the phalanx (8 cases) ; (3) excision of lesions of the second to fifth fingers followed by transfer of skin flaps from the thenar muscle area and full-thickness skin grafting (5 cases) , or excision of lesions of the thumb followed by abdominal-wall flap transfer (3 cases) . The patients were followed up for 12 months, and clinical efficacy was evaluated.Results:During the follow-up, no recurrence occurred in the 11 cases receiving direct excision and suture, with good appearances and longitudinal linear scars on the nail. Among the 8 cases receiving shaving therapy under a microscope, 4 experienced relapse during the follow-up of 6 - 12 months, and the nail/toenail plates were rough and poor in lustrousness in the other 4 without recurrence. No recurrence was observed in the 8 cases receiving excision of the lesions and full-thickness skin grafting, of whom 1 experienced skin graft necrosis, and skin grafts survived with obvious pigmentation in the other 7 cases. Among cases receiving excision of the lesions combined with transfer of skin flaps from the thenar muscle area or abdominal-wall flap transfer, no recurrence was observed, and all transferred flaps survived; good appearances, nearly normal color and gloss of nails were obtained in the cases after transfer of skin flaps from the thenar muscle area, while the color and gloss of postoperative nails were markedly different from those of normal nails in the cases receiving abdominal-wall flap transfer.Conclusion:For nail matrix nevi with a width of ≤ 3 mm, direct excision and suture with 1-to-2-mm margins are recommended; for those with a width of > 3 mm, excision of lesions combined with full-thickness skin grafting, transfer of skin flaps from the thenar muscle area or abdominal-wall flap transfer is recommended; the shaving procedure under a microscope should be used with caution.
5.Antigen sparing with influenza virus vaccine formulated with crude polysaccharides from Cistanche deserticola Y. C.Ma adjuvant
Peng XIAO ; Bing ZHAO ; Danyang WANG ; Ailian ZHANG
Chinese Journal of Microbiology and Immunology 2022;42(3):216-223
Objective:To investigate the antigen-sparing effects of crude polysaccharides from Cistanche deserticola Y. C.Ma (CPCD) for influenza virus vaccine (IVV). Methods:ICR mice were immunized subcutaneously with CPCD combined with different doses of IVV (0.01 μg and 0.1 μg). Hemagglutinin inhibition (HI) assay was used to detect HI titers in serum samples. Indirect ELISA was performed to detect the levels of specific IgG antibodies and their subtypes in serum samples. The proliferation of splenic lymphocytes was detected by MTT assay. The percentages of CD4 + , CD8 + and CD44 + T cells and the levels of IFN-γ in splenic cells isolated from the vaccinated mice were analyzed by flow cytometry. Results:CPCD significantly increased HI titers (234.67±47.70 vs 149.33±47.70, P<0.05), promoted the production of IgG ( A450 value: 1.16±0.63 vs 0.30±0.21, P<0.05) and IgG1 ( A450 value: 1.09±0.60 vs 0.26±0.21, P<0.05) and enhanced splenic lymphocyte proliferation ( P<0.05). CPCD also significantly up-regulated the expression of CD4 + [(41.97±4.58)% vs (25.43±1.48)%, P<0.05], CD8 + [(12.67±0.33)% vs (9.02±1.07)%, P<0.05], CD4 + CD44 + [(11.77±0.69)% vs (8.64±0.71)%, P<0.05] and CD8 + CD44 + [(6.70±0.67)% vs (4.66±0.39)%, P<0.05] T cell subsets as well as the secretion of IFN-γ in CD4 + [(1.36±0.07)% vs (0.87±0.06)%, P<0.05] and CD8 + [(2.09±0.20)% vs (1.42±0.08)%, P<0.05] T cells. In addition, there was no significant difference between CPCD combined with low-dose IVV group and high-dose IVV alone group ( P>0.05), implying a 10-fold antigen sparing. Conclusions:CPCD, as an adjuvant for influenza virus vaccine, could enhance humoral and cellular immune responses and reduce antigen dose, which might be a potential adjuvant for seasonal or pandemic influenza vaccines.
6.Optimal dose analysis of Th1/Th2 immuno-enhancement effects of cultivated Artemisia rupestris crude polysaccharides on foot-and-mouth disease inactivated vaccine via intramuscular route
Ruziwanguli YIMAMU ; Xiang WENG ; Peng XIAO ; Daocheng WU ; Hui CAO ; Ailian ZHANG
International Journal of Biomedical Engineering 2022;45(4):294-300
Objective:To investigate the optimal dose of Th1/Th2 immuno-enhancement effects of cultivated Artemisia rupestris L. crude polysaccharides (CARCP) on foot-and-mouth disease vaccine (FMDV) via the intramuscular route. Methods:ICR mice were intramuscularly immunized twice with different concentrations of CARCP mixed with FMDV at 2-week intervals. FMDV-specific antibodies, isotypes, and IgE in serum were detected by ELISA. Splenocyte proliferation was detected by MTT. T lymphocyte subsets and cytokines in the spleen were detected by flow cytometry. Clinical signs and local reactions at the injection site were monitored daily, and the body weight of mice was weighed after immunization.Results:The medium dose of CARCP could significantly improve FMDV-specific IgG, IgG 1, and IgG 2a antibody levels and the IgG 2a/IgG 1 ratio ( P<0.05) and lead to significant splenocyte proliferative responses ( P<0.01). The medium dose of CARCP could also significantly increase the level of CD3 +CD4 + and CD3 +CD8 + T cells as well as CD4 +/CD8 + ratio ( P<0.05), elicited the higher levels of IFN-γ in CD4 + T cells and CD8 + T cells ( P<0.05). No local adverse reactions at the injection site were observed after immunization. There was no significant difference in body weight or growth between each group( P>0.05). CARCP did not significantly induce an IgE response ( P>0.05). Conclusions:CARCP as an FMDV adjuvant promotes Th1/Th2 immune responses, especially in favor of the Th1 response, and has a certain safety profile. The best immune enhancement is achieved with CARCP at medium doses.
7.Predictive role of clinical features in patients with coronavirus disease 2019 for severe disease.
Juan MO ; Jiyang LIU ; Songbai WU ; Ailian LÜ ; Le XIAO ; Dong CHEN ; Yun ZHOU ; Lu LIANG ; Xiaofang LIU ; Jinjin ZHAO
Journal of Central South University(Medical Sciences) 2020;45(5):536-541
OBJECTIVES:
Since the outbreak of coronavirus disease 2019 (COVID-19), it has spread rapidly in China and many other countries. The rapid increase in the number of cases has caused widespread panic among people and has become the main public health problem in the world. Severe patients often have difficult breathing and/or hypoxemia after 1 week of onset. A few critically ill patients may not only rapidly develop into acute respiratory distress syndrome, but also may cause coagulopathy, as well as multiple organs failure (such as heart, liver and kidney) or even death. This article is to analyze the predictive role of clinical features in patients with COVID-19 for severe disease, so as to help doctor monitor the severity-related features, restrain the disease progress, and provide a reference for improvement of medical treatment.
METHODS:
The clinical data of 208 patients with COVID-19 who were isolated and treated in Changsha Public Health Treatment Center from January 17, 2020 to March 14, 2020 were collected. All patients were the mild and ordinary adult patients on admission, including 105 males and 103 females from 19 to 84 (median age 44) years old. According to the "Program for the diagnosis and treatment of novel coronavirus (COVID-19) infected pneumonia (Trial version 7)" issued by the General Office of National Health Committee and Office of State Administration of Traditional Chinese Medicine as the diagnostic and typing criteria. According to progression from mild to severe disease during hospitalization, the patients were divided into a mild group (=183) and a severe transformation group (=25). The clinical features such as age, underlying disease, blood routine, coagulation function, blood biochemistry, oxygenation index, and so on were analyzed. Among them, laboratory tests included white blood cell (WBC), lymphocytes (LYM), neutrophil (NEU), hemoglobin (Hb), platelet (PLT), prothrombin time (PT), plasma fibrinogen (Fib), activated partial prothrombin time (APTT), thrombin time (TT), -dimer, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (Cr), creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP), and oxygen partial pressure in arterial blood. Partial pressure of oxygen in arterial blood/fractional concentration of inspiratory oxygen (PaO/FiO) was calculated. The variables with statistical significance were analyzed by logistic regression analysis.
RESULTS:
Patients in the severe transformation group had more combined underlying diseases than those in the mild group (<0.05). From the perspective of disease distribution, patients in the severe transformation group had more combined hypertension (<0.05). In the severe transformation group, PT was significantly longer, the levels of Fib, ALT, AST, CK, LDH, and CRP were significantly higher than those in the mild group (<0.05 or <0.001), while LYM, ALB, and PaO/FiO were significantly lower than those in the mild group (<0.05 or <0.001). Logistic regression analysis was performed on clinical features with statistically significant differences. Combined with hypertension, LYM, PT, Fib, ALB, ALT, AST, CK, LDH, and CRP as independent variables, and having severe disease or not was the dependent variable. The results show that combined hypertension, decreased LYM, longer PT, and increased CK level were independent risk factors that affected the severity of COVID-19 (<0.05).
CONCLUSIONS
The patients with mild COVID-19 who are apt to develop severe diseases may be related to combined hypertension, decreased LYM, and longer PT, and increased CK level. For the mild patients with these clinical features, early intervention may effectively prevent the progression to severe diseases.
Adult
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Aged
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Aged, 80 and over
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Betacoronavirus
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China
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Coronavirus Infections
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diagnosis
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physiopathology
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Disease Progression
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Female
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Hospitalization
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Humans
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Male
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Middle Aged
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Pandemics
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Pneumonia, Viral
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diagnosis
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physiopathology
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Retrospective Studies
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Young Adult
8.Development and systematical evaluation of an up-converting phosphor technology based lateral flow assay for quantitative detection of Burkholderia pseudomallei.
Fei HUA ; Pingping ZHANG ; Xiaoying WANG ; Lei ZHOU ; Yong ZHAO ; Xiao LIU ; Chunfeng LI ; Ruifu YANG ; Ailian YU
Chinese Journal of Preventive Medicine 2015;49(2):166-171
OBJECTIVETo develop an up-converting phosphor technology-based lateral-flow (UPT-LF) assay for rapid quantitative detection of Burkholderia pseudomallei on site.
METHODSThe strip Bps-UPT-LF strip was prepared with up-converting phosphor (UCP) particles as the bio-label using double-antibody sandwich method. Detection performance, including sensitivity, quantitative accuracy, precision, and specificity, were first evaluated using bacterial suspensions of Burkholderia pseudomallei, the related species and the strains which had similar routes of transmission with serial standard concentrations diluted by phosphate buffer, then biological and chemical reagents and simulated samples with series concentrations were employed for sample tolerance evaluation, while the operation error during on site detection was also evaluated through adjusting liquid measure.
RESULTSThe whole detection was accomplished within 20 minutes, and the sensitivity was 10(4) CFU/ml with linear quantitative range from 10(4) CFU/ml to 10(7) CFU/ml, which covered four orders of magnitude. Bps-UPT-LF strip demonstrated high specificity with the absence of any false-positive result even at 10(7) and 10(8) CFU/ml of non-specific bacterial contamination. Not only Bps-UPT-LF strip could tolerate to high concentration of the extreme acid and basic matter (pH 1-12), saline matter (≤ 2 mol/L mixture of NaCl and KCl), viscous materials (≤ 50 g/L of PEG 20000 and ≤ 20% of glycerol) and bio-macromolecule (≥ 400 g/L of bovine serum albumin or ≥ 80 g/L of casein), but also it can directly detect animal, environmental and powder specimen, such as ≥ 400 g/L of milk powder, flour powder, fruit juice, fresh and decomposed viscera, and ≤ 200 g/L of putty powder, sucrose, gourmet powder, and soil. Operation errors of liquid measure had few effects on sensitivity and specificity, including -50%-200% of sample, -22%-44% of sample-treating buffer and -30%-30% of loading mixture.
CONCLUSIONThe good detection performance and tolerance performance bring the bright future for Bps-UPT-LF strip to detect Burkholderia pseudomallei on site rapidly and quantitatively for nature foci surveillance and anti-bioterrorism.
Animals ; Burkholderia pseudomallei ; Immunochromatography ; Sensitivity and Specificity
9.National external quality assessment for HLA low-resolution molecular typing: 2005 -2008 activities
Ailian HEI ; Ziaoyang ZHOU ; Yao XIAO ; Dapeng DAI ; Jianping CAI
Chinese Journal of Laboratory Medicine 2009;32(6):701-704
Objective National external quality assessment (EQA) results from 2005 to 2008 for HLA class Ⅰ (A, B) and class Ⅱ (DRB1) low-resolution DNA typing were summarized with the goal of exploring strategies to assure and improve HLA DNA typing performance in clinical testing. Methods HLA allele results from the four consecutive years EQA events were analysed. Different kinds of errors were described and classified, and the possible causes were discussed. Results Participant laboratories were increasing in the four consecutive years with the number of 22, 28, 47 and 61 in 2005, 2006, 2007 and 2008,respectively. 2 844 HLA DNA typings were returned from the participants during the 4 years EQA surveys, and overall 30 errors (1.05%) were identified. These 30 errors were classified into two major types of errors including 25 technical genotyping errors and 5 human errors. The proportion of laboratory participants which made mistakes was 13. 6%, 10. 7%, 10. 6% and 16.4% in 2005, 2006, 2007 and 2008, respectively. Conclusions Above 10% of participant laboratories exhibited errors in the four consecutive years HLA molecular typing EQA surveys. Relevant important attentions should be greatly paid to clinical HLA molecular typing test.
10.Analysis of physical examinations and correlation factors in bank employees
Aizhong CHEN ; Ailian CHEN ; Lanxiang XIAO ; Hong XU
Chinese Journal of Practical Nursing 2008;24(15):14-15
Objective We aimed to analyze the results of physical examinations in bank employees and understand the self-health care consciousness of them in order to establish health education method for the employees.Methods We collected data of physical examinations for 904 bank employees and analyzed the results statisticaUy.Results There were 510 employees who got abnormal results,accounting for 56.4%.The first four diseases were ordered as follows:hyperlipoidemia,hepar adiposum,high blood pressure and hyperuricacidemia.Moreover,the incidence increased with the increasing ages.Besides,the incidence of illness was closely correlated with the employees'living styles. Conclusions We should strengthen the health education and behavior intervention for bank employees in order to urge them to drop off bad living habits self-consciously and establish benign living styles.

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