1.The Analysis of Influencing Factors of Progressive Hearing Loss in Children with Large Vestibular Aqueduct Syndrome
Lin DENG ; Xiaohua CHENG ; Lihui HUANG ; Hui LIU ; Dongxin LIU ; Cheng WEN ; Yue LI ; Xiaozhe YANG ; Junfang XIAN
Journal of Audiology and Speech Pathology 2024;32(6):500-506
Objective To study the prognostic factors of progressive hearing loss among children with large vestibular aqueduct syndrome(LVAS).Methods The clinical data of 49 children(95 ears)with LVAS who re-ceived at least two hearing tests from January 2017 to January 2023 in our hospital were retrospectively analyzed,and they were divided into two groups according to the progression of hearing loss:the stable group(55 ears)and the progressive group(40 ears).The effects for progressive hearing loss of initial age,gender,laterality,imaging features,audiometric data,and incomplete partition type Ⅱ(IP-Ⅱ)and SLC26A4(type A,B,C,D)genotypes were analyzed by univariate and multivariate Cox regression analysis.The potential prognostic factors were further verified by Kaplan-Meier survival analysis.Results Each dB decrease in the initial average hearing threshold in-creased the expected hazard by 7.03%(P=0.02).Incomplete partition type Ⅱ(IP-Ⅱ)was associated with 5.11 hazard ratio(95%CI,1.81 to 14.45,P=0.002).Genotype C was associated with 6.13 hazard ratio for progressive hearing loss(95%CI,2.07 to 18.13,P=0.001).Conclusion The initial average hearing threshold,IP-Ⅱ,and SLC26A4 genotype C were significant effect factors of progressive hearing loss in patients with LVAS.This could predict the progression of hearing loss in children with LVAS and help identify patients at high risk for progressive hearing loss.
2.Analysis of the difference between genotype and hearing phenotype in 142 infants with biallelic allele variant in GJB2
Yu RUAN ; Cheng WEN ; Xiaohua CHENG ; Wei ZHANG ; Jinge XIE ; Yue LI ; Lin DENG ; Lihui HUANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(9):569-573
OBJECTIVE To analyze the difference of genotypes and hearing phenotypes in infants with biallelic allele variant in GJB2,and to provide reference for clinical practice. METHODS One hundred and forty-two subjects with biallelic allele variant in GJB2 were recruited in Beijing Tongren Hospital from August 2012 to March 2024. All subjects received universal newborn hearing screening(UNHS),neonatal deafness genetic screening and audiological tests. The subjects were divided into three groups according to the genotypes:T/T groups(truncated/truncated mutations,59 cases),T/NT group(truncated/non-truncated mutations,50 cases) and NT/NT group(non-truncated/non-truncated mutations,33 cases). Three groups of genotypes,newborn hearing screening results,age at first diagnosis and hearing diagnosis results were analyzed. RESULTS The homozygous mutation of c.235delC/c.235delC was the dominant in T/T group(57.63%),the compound heterozygous mutation of c.235delC/c.109G>A was the dominant in T/NT group(74.00%),and the homozygous mutation of c.109G>A/c.109G>A was the dominant in NT/NT group(96.97%). The overall refer rate of UNHS was 80.28%,and the refer rate of T/T group was 89.83%,which was significantly higher than that of T/NT group 70.00%(P=0.009). The age of first diagnosis of 142 cases was (3.70±1.56) months,there was no significant difference between the three groups(P>0.05). In 142 cases,104 cases with hearing loss accounted for 73.24%,38 cases with normal hearing accounted for 26.76%. The proportion of confirmed hearing loss in T/T group was 100.00%,which was significantly higher than that in T/NT group 52.00%(P<0.001) and NT/NT group 57.58%(P<0.001). In side of hearing loss,of the 104 patients with hearing loss,86 cases(82.69%) had bilateral hearing loss and 18 cases(17.31%) had unilateral hearing loss. The proportion of bilateral hearing loss in T/T group was 100.00%,which was significantly higher than that in T/NT group 57.69%(P<0.001) and NT/NT group 63.16%(P<0.001). Among 190 ears of 104 patients with hearing loss,the degree of hearing loss was predominantly mild to moderate(63.16%),followed by profound(24.74%) and severe(12.10%). Among them,the T/T group was mainly marked by severe to profound hearing loss(58.47%),while both the T/NT group and the NT/NT group were mainly characterized by mild hearing loss(58.54% and 74.19%),and the differences among the three groups were statistically significant(P<0.001). CONCLUSION In the T/T group,all patients were diagnosed as bilateral hearing loss at first diagnosis,and was mainly severe and profound hearing loss. The bilateral and unilateral hearing loss were 52.00% and 57.58% in the T/NT group and NT/NT group at first diagnosis respectively,and was mainly mild hearing loss.
3.Analysis of sequential chemotherapy efficacy in ovarian epithelial carcinoma, fallopian tube carcinoma and primary peritoneal carcinoma
Xiaoyan SHEN ; Xiaoping LI ; Yue WANG ; Yan WU ; Yi LI ; Yingchao YANG ; Lihui WEI ; Yuan FAN ; Ziqian TANG
Chinese Journal of Obstetrics and Gynecology 2024;59(5):383-390
Objective:To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma.Methods:A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel′s Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups.Results:(1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups ( Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions:Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.
4.Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone and construction of prediction model
Jianlong LI ; Ping YUE ; Xianzhuo ZHANG ; Yong ZHANG ; Ling'en ZHANG ; Lihui ZHAO ; Hengwei ZHANG ; Yanyan LIN ; Longlong YIN ; Xun LI ; Wenbo MENG
Chinese Journal of Digestive Surgery 2023;22(7):899-908
Objective:To investigate the risk factors of acute biliopancreatic complica-tions in patients of pregnancy combined with gallbladder stone and construction of prediction model.Methods:The retrospective case-control study was constructed. The clinical data of 98 patients of pregnancy combined with gallbladder stone who were admitted to the First Hospital of Lanzhou University from September 2011 to October 2022 and 53 patients of pregnancy combined with gallbladder stone who were admitted to Gansu Provincial Hospital May 2014 to October 2021 were collected. The age of 151 patients was 29(25,32)years. Observation indicators: (1) situations of patients of pregnancy combined with gallbladder stone; (2) risk factors of acute biliopancreatic com-plications in patients of pregnancy combined with gallbladder stone; (3) construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multi-variate analyses were conducted using the Logistic regression model. Nomogram prediction model was conducted, and the receiver operating characteristic (ROC) curve was used to evaluate discri-mination of the nomogram predic-tion model. The calibration curve and clinical decision curve were used to evaluate calibration and net clinical benefit of the nomogram prediction model. Internal validation of the prediction model was performed by applying 10-fold cross-validation. Results:(1) Situations of patients of pregnancy combined with gallbladder stone. The total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), gesta-tional period (early, mid, late), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were (4.9±1.4)mmol/L, 1.88(1.22,2.93)mmol/L, 1.48(1.22,1.83)mmol/L, (2.8±0.9)mmol/L, 13, 75, 58, 37, 45, 69, 86, 65, 37, 114, 89, 62, 38, 113 in the 151 patients of pregnancy combined with gallbladder stone. Of the 151 patients, the age, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were 31(28,37)years, 3, 30, 36, 29, 40, 32, 37, 26, 43, 4, 65 in 69 cases without symptom, versus 27(24,31)years, 10, 45, 22, 57, 25, 5, 77, 63, 19, 34, 48 in 82 cases combined with acute biliopancreatic complications, showing significant differences in the above indicators between them ( Z=?3.636, ?2.385, χ2=11.544, 32.862, 23.729, 25.310, P<0.05). Five of the 82 patients of pregnancy combined with gallbladder stone missed data of prepregnancy body mass index. Of the 82 patients, there were 42 patients of simple acute cholecystitis, 40 patients of common bile duct stone and/or acute biliary pancreatitis including 18 cases of common bile duct stone, 13 cases of acute biliary pancreatitis and 9 cases of common bile duct stone combined with acute biliary pancreatitis. (2) Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Results of multivariate analysis showed that primipara, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone ( odds ratio=3.102, 6.305, 3.674, 6.686, 95% confidence interval as 1.280?7.519, 1.886?21.080, 1.457?9.265, 1.984?22.528, P<0.05). Results of multivariate analysis in further analysis showed that primipara, non solitary stone, gallbladder wall thickness ≥4 mm were independent risk factors of simple acute cholecystitis in patients of pregnancy combined with gallbladder stone ( odds ratio=3.671, 8.905, 7.137, 95% confidence interval as 1.386?9.723, 2.332?34.006, 1.902?26.773, P<0.05), and age, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of common bile duct stone and/or acute biliary pancreatitis in patients of pregnancy combined with gallbladder stone ( odds ratio=0.883, 5.361, 5.472, 8.895, 95% confidence interval as 0.789?0.988, 1.062?27.071, 1.590?18.827, 2.064?38.325, P<0.05). (3) Construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The nomogram prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone was constructed based on the clinical factors of age, primipara, stone type, diameter of stone and gallbladder wall thickness. The area under the curve (AUC) of ROC curve of prediction model was 0.869 (95% confidence interval as 0.813?0.923), indicating that the prediction model with good predictive ability. Results of Hosmer-Lemeshow test showed a good fit ( χ2=5.680, P>0.05), indicating that the prediction model with good calibration. Results of decision curve analysis showed the prediction model with high net clinical benefit. Results of internal validation of the prediction model based on 10-fold cross-validation showed the AUC of ROC curve for the cross-validation sample was 0.833, indicating that the prediction model with good stability. Conclusions:Primigravida, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm are independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The prediction model for acute biliopancreatic complications has good predictive ability.
5.Research progress on platelet rich plasma in management of patients with knee osteoarthritis
Yachong YANG ; Shichao SHUAI ; Lihui YUE ; Jing HAN ; Yong WANG ; Xichun ZHU
Chinese Journal of Blood Transfusion 2023;36(1):90-92
Knee osteoarthritis (KOA) is a common chronic degenerative disease of cartilage, which often occurs in middle-aged and elderly patients. It can cause joint swelling, pain and limited movement. With the aging population gradually increasing in China, the prevalence of KOA is also increasing, imposing burdens on patients, families and society. At present, the clinical treatment methods for KOA mainly include physical exercise therapy, non-steroidal analgesic drug therapy, intra-articular hormone injection therapy and surgical treatment, which can improve symptoms and reduce pain but cannot effectively cure KOA. With the development of medicine, platelet-rich plasma (PRP) therapy, as a new treatment method, has the effects of nerve repair and pain relief, and has become a new choice for the treatment of KOA. This article reviews the application of PRP in KOA, so as to provide a new perspective for clinical treatment of knee osteoarthritis KOA.
6.A brief analysis of the American Cancer Society′s Clinical Practice Guideline—Head and Neck Cancer Survivorship Care Guideline
Yu LI ; Lihui LIU ; Zengxia SHI ; Chunxiang SU ; Zhiqi CHEN ; Zipan WANG ; Jing WANG ; Shujin YUE
Chinese Journal of Practical Nursing 2019;35(3):161-165
With the construction and development of head and neck tumor, diagnosis and treatment technology and survival rate of patients have been improved in different degrees. Nurses play an important role as managers and practitioners in the treatment and rehabilitation of patients with head and neck tumors, and it is very important to evaluate and manage the treatment and prognosis of head and neck tumor patients scientifically. In this context, the American Cancer Society launched the Head and Neck Cancer Survivorship Care Guideline in 2017 and was endorsed by the American Society for Clinical Oncology. This paper mainly discusses the forming process of the guidelines, the main points of the consensus of experts, the guiding role of the guidelines in clinical work and the obstacles and limitations of the guidelines.
7.Survey of the acceptance status of HPV self-sampling screening in female population for cervical cancer
Yun ZHAO ; Qi LIAO ; Xin MI ; Mingzhu LI ; Chao ZHAO ; Shuhui CUI ; Jingran LI ; Yue WANG ; Jianliu WANG ; Lihui WEI
Chinese Journal of Obstetrics and Gynecology 2019;54(5):312-317
Objective To investigate the acceptance of HPV self-sampling mode in cervical cancer screening population and explore its feasibility. Methods From March 5 to 15, 2018, researchers investigated women who participated in cervical cancer screening organized by Beijing Shunyi Women's and Children's Hospital in the form of questionnaires. Questionnaires were conducted on their acceptance status and the factors that affect the self-sampling experience. The specific contents of the questionnaires were as follows: (1) the experience of using self-sampling included operability, comfortable, sample time-consuming, bleeding or not after sampling; (2) psychological changes after self-sampling, including the willingness to accept self-sampling again, the worrying problems during self-sampling process. According to whether or not have operating video guidance, the self-sampling experience and psychological changes after self-sampling were compared. Results (1) There were 1 375 women participated in the questionnaire survey, and 86.55% (1 190/1 375) of them thought the self-sampling was convenient, 78.40% (1 078/1 375) thought it was not uncomfortable, 88.58% (1 218/1 375) thought the sampling time was fast (less than 5 minutes), 94.04% (1 293/1 375) self-sampling without bleeding; and 83.27% (1 145/1 375) were willing to self-sampling for cervical cancer screening again, 85.82% (1 180/1 375) were afraid of inaccurate sampling. (2) Among the 1 375 women, 1 202 were in the video guidance group and 173 were in the non-guidance group. The self-sampling experience of women in video guidance group was better than those of non-guidance group in operability, comfortable, sampling time-consuming and bleeding after sampling. The proportion of women who willing to self-sampling again was higher than that of non-guidance group (86.69% vs 59.54%, respectively). The proportion of women who worried operating incorrectly was lower than that of non-guidance group (11.23% vs 32.37%, respectively). The differences were significant (all P<0.05). Conclusions Self-sampling for HPV testing in cervical cancer screening is easy to operate and has little discomfort complaint. It is feasible in cervical cancer screening. Operational video guidance during the screening process could effectively improve the women's experience and willingness to self-sampling again in the future.
8.A brief analysis of Clinical Best Practice Guidelines:Assessment and Management of Pain(Third Edition)by Registered Nurses'Association of Ontario in 2013
Qi LIU ; Dongqin KANG ; Zipan WANG ; Jing WANG ; Shujin YUE ; Yu LI ; Lihui LIU ; Hong GUO ; Zhiqi CHEN
Chinese Journal of Modern Nursing 2018;24(34):4093-4097
With the continuous development of health care, people's awareness of health care is gradually enhanced. Pain has become an important part of disease rehabilitation and nursing. The research and evidence of pain assessment and management are increasing year by year. As the most direct assessor and manager of patients' pain, it is particularly important for nurses to identify and effectively manage different types of pain as soon as possible. In this background, the Registered Nurses' Association of Ontario (RNAO) released Clinical Best Practice Guidelines:Assessment and Management of Pain(Third Edition)in 2013. This article mainly introduces the development, application scope, methodology, main content, quality evaluation and subsidiary information of the guide.
9.Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-Rand in diabetic KKmice.
Quan LIU ; Shuainan LIU ; Lihui GAO ; Sujuan SUN ; Yi HUAN ; Caina LI ; Yue WANG ; Nan GUO ; Zhufang SHEN
Acta Pharmaceutica Sinica B 2017;7(4):461-469
Refined-JQ (JQ-R) is a mixture of refined extracts from(Ranunculaceae),(Leguminosae) and(Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKmice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKmice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-B p65), inhibitor of NF-B (IB), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKmice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.
10.Study on clinical management of HPV+/Pap-during cervical cancer screening
Aijuan HUANG ; Yun ZHAO ; Xiaolian ZOU ; Jin YAN ; Chao ZHAO ; Shuhui CUI ; Yanyan LI ; Lihua REN ; Jingran LI ; Mingzhu LI ; Yue WANG ; Jianliu WANG ; Lihui WEI
Chinese Journal of Obstetrics and Gynecology 2017;52(11):745-750
Objective To study the clinical management way for HPV+/papanicolaou (Pap)-during cervical cancer screening.Methods To analyze retrospectively the data from the patients who had loop electrical excision procedure (LEEP) for biopsy confirmed cervical intraepithelial neoplasia (CIN)Ⅱ in Peking University People's Hospital from Jan.2010 to Dec.2014.Results (1) For biopsy confirmed CINⅡ,HPV positive rate was 98.5% (135/137),Pap test positive [≥atypical squamous cell of undetermined significance (ASCUS)] rate was 69.3% (95/137),there was significant difference between them (x5=43.32,P<0.01).(2) For the 42 patients with HPV+/Pap-,whose cytology slides were reviewed again.Among them,the interpretations of there were 16 cases confirmed as the same before,while 26 cases were changed to abnormal (≥ASCUS).Cytology be misdiagnosed was 19.0% (26/137) at the first review.Among the 26 cases,13 (50.0%) cases were missed for the little amount of abnormal cells,8 (30.8%) cases for mild atypical morphology changed;the other 5 (19.2%) cases missed for stain problems.(3) For the cervical LEEP samples,37 cases of the pathology diagnosis were upgrade to CIN Ⅲ+,among them,2 cases of microinvasive cervical carcinoma,1 case of invasive cancer,34 cases of CIN Ⅲ;37 cases were CINⅠ or no lesion found;63 cases were still CIN Ⅱ.Four to six months later after LEEP,the cytology abnormal rate was 11.7% (16/137),and the HR-HPV positive rate was 34.3% (47/137).Conclusions Compared with cytology alone,cytology combined with HPV testing increase the sensitivity of cervical high grade lesion.For the cases of HPV+/Pap-cases,the cytology slides should be reviewed.The quality control of cervical exfoliate sample collection and interpretation should be strengthened.LEEP procedure is not only a treatment method,but also it could provide samples to confirm the diagnosis.

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