A study on epithelial cell adhesion molecule targeted nucleic acid aptamer drug conjugate in gastric cancer targeted treatment / 中华消化外科杂志

Objective:To investigate the affinity and toxicity of epithelial cell adhesion molecule (EpCAM) targeted nucleic acid aptamer drug conjugate SYL3C-MMAE on human gastric epithelial cells GES-1 (hereinafter referred to as GES-1 cells) and human gastric cancer cells AGS and MKN45 (hereinafter referred to as AGS cells and MKN45 cells).Methods:The experimental study was conducted. The expression level of EpCAM in gastric cancer tissues was detected using immunohistochemistry. The mRNA expression level of EpCAM in gastric cancer tissues was detected using real-time fluorescence quantitative PCR (RT-PCR). The expression level of EpCAM protein in GES-1, AGS and MKN45 cells was detected using Western blot. The affinity of SYL3C on GES-1, AGS and MKN45 cells was detected using flow cytometry. SYL3C-MMAE was synthesized through a thiol-maleimide reaction. The toxicity of drugs on GES-1, AGS and MKN45 cells was detected using CCK-8 assay. The cell cycle condition of GES-1, AGS and MKN45 cells after drug treatment was detected using propidium iodide (PI) staining. Observation indicators: (1) expression of EpCAM in gastric cancer; (2) affinity of antibodies targeting EpCAM and SYL3C on GES-1, AGS and MKN45 cells; (3) situation of drug synthesis; (4) drug toxicity and inhibition of cell cycle. Measurement data with normal distribution were represented as Mean± SD. One-way ANOVA was used for comparison among multiple groups, and pairwise comparison was conducted using the least significant difference test. Comparison of unequal variances was conducted using the Welch' t test. Measurement data with skewed distribution were represented as M(IQR), and comparison between groups was conducted using the paired rank sum test. Count data were described as absolute numbers, comparison between groups was conducted using the paired chi-square test. Results:(1) Expression of EpCAM in gastric cancer. Results of immunohistochemistry on tissue microarrays showed that the positive rate of EpCAM was 82.9%(29/35) and 22.9%(8/35) in the 35 pairs of gastric cancer and its adjacent tissues (normal tissues), respectively, showing a significant difference between them ( P<0.05). Results of RT-PCR showed that the mRNA relative expression levels of EpCAM was 1.23 (4.13) and 4.04 (1.72) in 12 pairs of gastric cancer and its adjacent tissues respectively, showing a significant difference between them ( Z=-2.67, P<0.05). Results of Western blot showed that the relative expression levels of EpCAM protein in GES-1, AGS, and MKN45 was 0, 1.00, and 0.27, respectively, with the expression level of EpCAM protein in AGS cells as the standard. (2) Affinity of antibodies targeting EpCAM and SYL3C on GES-1, AGS and MKN45 cells. Results of flow cytometry showed that antibodies targeting EpCAM and SYL3C had good affinity on AGS and MKN45 cells but no affinity on GES-1 cells. (3) Situation of drug synthesis. Results of mass spectrometry showed that the drug solution of compound formed by connecting SYL3C with monomethylorestatin E (VcMMAE) exhibited a strong peak at the molecular weight position of 16 355, consistent with the expected molecular weight of the SYL3C-MMAE complex, indicating that SYL3C-MMAE was successfully synthesized. (4) Drug toxicity and inhibition of cell cycle. Results of CCK-8 assay showed that the half maximal inhibitory concentration (IC 50) of VcMMAE on GES-1, AGS and MKN45 cells was 123.00, 30.48 and 51.83 nmol/L, respectively. The IC 50 of SYL3C-MMAE on GES-1, AGS and MKN45 cells was 241.80, 20.66 and 27.64 nmol/L, respectively. Results of PI staining and flow cytometry showed that both VcMMAE and SYL3C-MMAE could induce G2/M phase blockage in the cell cycle of GES-1, AGS and MKN45 cells. Conclusion:The SYL3C-MMAE has a good affinity on gastric cancer cells. Compared with VcMMAE, SYL3C-MMAE exhibits efficient inhibition on gastric cancer cells, but less influence on normal cells.

The latest research progress of the mechanism of drug resistance to TKIs in clinical treatment of gastrointestinal stromal tumor / 肿瘤

Gastrointestinal stromal tumor(GIST)is the most common mesenchymal tumor of the gastrointestinal tract.The pathogenesis of most GIST is driven by the gain-of-function mutations of KIT proto-oncogene receptor tyrosine kinase(c-KIT)or platelet-derived growth factor receptor alpha(PDGFRA)gene.The original clinical treatment for GIST was surgical resection only.With the advent of tyrosine kinase inhibitors(TKIs)represented by imatinib,GIST therapy has entered the era of targeted therapy.TKIs have achieved significant clinical efficacy in GIST treatment.To date,several TKI drugs have been approved for clinical application,which has greatly improved the survival time of GIST patients,but the ensuing drug resistance problem is a difficult problem that requires an urgent solution.Currently,it has been confirmed that the main reason for drug resistance to TKI in GIST is the secondary mutation of different exons of c-KIT or PDGFRA.However,even GIST patients with the same exon mutation still reacts very differently to TKIs,suggesting that there may be other mechanisms acting in parallel with c-KIT and PDGFRA.Thanks to the development and application of molecular biological technologies such as CRISPR gene editing technology,the genetic differences between TKI drug resistant and sensitive GIST are becoming clearer and clearer,and many more new mechanisms have been identified.This paper summarizes the latest research progress of the mechanism of drug resistance to the most commonly used TKIs in the clinical treatment of GIST.

From basic to clinical:Advances in research on ETV1 / 肿瘤

ETS variant gene 1(ETV1)is an oncogene that plays an important role in embryonic development and malignant progression of tumors.Chromosomal translocations,gene amplifications,and activation of the mitogen activated protein kinase(MAPK)signal pathways lead to the up-regulation of ETV1,and then ETV1,as a transcription factor,regulates the expression of downstream target genes by binding to their promoters or enhancers,thereby playing a pivotal role in the occurrence and development of prostate cancer,gastrointestinal stromal tumor(GIST)and breast cancer.ETV1 is also a potential tumor biomarker,which has clinical value in diagnosis and prognostic evaluation in various tumors,and strategies targeting ETV1 can provide new treatment options to tumor patients.This article discusses the mechanisms of ETV1 activation and pro-oncogenic mechanisms driven by ETV1,and summarizes and prospects the clinical application of ETV1 as a tumor biomarker and therapeutic target.

Analysis on formula of Mongolian medicine for prevention of COVID-19 / 中国中药杂志

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.

Application of imatinib plasma concentration monitoring in the whole process management of gastrointestinal stromal tumor patients / 中华胃肠外科杂志

Objective@#To investigate the significance of monitoring imatinib mesylate (IM) plasma concentrations in patients with gastrointestinal stromal tumor (GIST).@*Methods@#A retrospective descriptive study was carried out. Inclusion criteria: (1) patients with GIST confirmed by postoperative pathology or puncture pathology receiving maintenance therapy of IM; (2) administration of same dose of IM for at least 4 weeks (achieving steady - state plasma concentration). Patients who had severe organ dysfunction, received IM generics, or received IM simultaneously with other drugs significantly affecting IM pharmacokinetic were excluded. A total of 185 patients at the GIST Clinic of Renji Hospital, Shanghai Jiaotong University School of Medicine from August 2018 to May 2019 were enrolled, including 114 males (61.6%) and 71 females (38.4%) with a median age of 60 years old (range, 30-89 years), and 63 advanced cases. Patients receiving preoperative or postoperative adjuvant therapy were given IM 400 mg QD; patients with KIT exon 9 mutation or with disease progression during IM 400 mg QD treatment were given IM 600 mg QD. If the patient had adverse reactions such as myelosuppression during the medication, IM would be reduced or given BID per day. The peripheral venous blood was collected (22 to 24 hours after the last dose for patients who took IM QD and 2 hours before the first dose per day for those who took IM BID). IM plasma concentration was measured through high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Correlation analysis between IM plasma concentration results and clinical data was performed using linear regression analysis.@*Results@#A total of 241 stable blood samples of IM plasma concentration from 185 patients were finally collected. The IM plasma concentrations were significantly different between the doses of 300 mg/d and 400 mg/d [(942.4±433.5) μg/L vs. (1340.0±500.1) μg/L, t=6.317, P<0.001], and between 400 mg/d and 600 mg/d [(1340.0±500.1) μg/L vs. (2188.0±875.5) μg/L, t=3.557, P=0.004]. Among the blood samples of 57 patients receiving IM 300 mg/d, the IM plasma concentration of the advanced patients was significantly lower than that of the non-advanced patients [(795.6±225.8) μg/L vs. (992.2±484.4) μg/L, t=2.088, P=0.042]. Among the 137 blood samples of patients receiving IM 400 mg/d, the IM plasma concentration was higher in patients aged >60 years than those aged ≤60 years [(1461.0±595.3) μg/L vs. (1240.0±380.9) μg/L, t=2.528, P=0.013] and the IM plasma concentration of cases with diarrhea was significantly lower than that of those without diarrhea [(745.8±249.6) μg/L vs. (1382.0±486.9) μg/L, t=6.794, P<0.001]. Gender, primary location, surgical procedure, mutated gene, mutation type, or time of administration was associated with IM plasma concentration no matter in patients taking IM doses of 400 mg/d or 300 mg/d (all P>0.05). Regression analysis showed that body mass (P=0.004 and P=0.019), body mass index (P=0.016 and P=0.042), and body surface area (P=0.007 and P=0.028) were all negatively correlated with IM plasma concentrations in patients taking IM doses of 300 mg/d and 400 mg/d. Within the 137 patients who received a fixed oral dose of 400 mg/d IM, 17 patients received oral 200 mg BID, whose IM plasma drug concentration was not significantly different compared with that of 120 patients who received 400 mg IM QD [(1488.0±408.3) μg/L vs. (1319.0±509.7) μg/L, t=1.307, P=0.193].@*Conclusions@#Monitoring IM plasma concentration is significant throughout the whole process of management of GIST patients receiving IM treatment. In particular, regular monitoring IM plasma concentration and developing appropriate treatment strategies can bring better therapeutic benefits for patients with low doses, diarrhea, advanced condition and older age.

Minutes of the 103rd annual meeting of American College of Surgeons / 中华消化外科杂志

The 103rd annual meeting of American College of Surgeons (ACS) was held in Santiago on 22-26 October 2017.The annual meeting of ACS is not only the largest clinical surgical meeting in the world,but also a platform for global surgeons to learn from each other and enhance communication and friendship.The theme of this conference is to do what's right for the patients.This is not only the discussion in the field of surgical technology,but also the related contents,including medical education,professional ethics and humanities.This conference discussed the new progress of surgical treatment,which will have an aspiring impact on surgical practice and professional technology development,and further benefit the patients.

Protective effect of cornel iridoid glycoside on hepatocytes injured by D-galactosamine/tumor necrosis factor-α / 中国药理学通报

Aim To determine the effect of cornel iri-doid glycoside ( CIG ) on human hepatocyte cell line (L-02) injured by D-galactosamine (GalN) and tumor necrosis factor-α( TNF-α) .Methods Firstly, CIG was extracted , separated and purified . Cell lesion model injured by D-GalN/TNF-αwas tested by MTT method.T-AOC, SOD, MDA and calcium ion concen-tration were taken as indicators to study the effects of CIG on L-02 cell injured by D-GalN/TNF-α.The ex-pression of p-PERK, p-eIF-2α, caspase-3 protein were detected by Western blot .Results 44 mg · L-1 D-GalN and 100 μg · L-1 TNF-αwere suitable for L-02 cell lesion model.CIG high, middle, low concentra-tion group could significantly increase the L-02 cell ac-tivity by 21％, 13％, 8％, respectively and SOD activity and T-AOC ability as well compared with model group.At the same time, they markedly reduced the MDA activity except the low concentration .Three con-centrations of CIG could reduce the expression of endo-plasmic reticulum stress related protein PERK , eIF-2αand apoptosis-associated protein caspase-3. Conclu-sions CIG could protect L-02 cells injured by D-GalN/TNF-α.Increasing the cellular antioxidant abili-ty, reducing the damage of endoplasmic reticulum stress and the expression of apoptosis-associated protein may be the possible mechanism .

Clinicopathological classification and prognostic factors of gastrointestinal neuroendocrine neoplasms: an analysis of 119 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, pathological classification and prognostic factors of gastrointestinal neuroendocrine neoplasms (GI-NENs).</p><p><b>METHODS</b>Clinicopathological data of 119 GI-NENs patients at Shanghai Renji Hospital from November 2007 to December 2016 were analyzed retrospectively. According to the classification and grading criteria of the WHO Neuroendocrine Tumor 2010 edition, patients were classified pathologically to realize the malignant degree of tumors. The overall survival rate was calculated by Kaplan-Meier curve, the prognostic risk factors were analyzed by Cox regression model, and the factors including the platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) were included in the analysis in addition to the routine clinicopathological factors.</p><p><b>RESULTS</b>Of 119 patients with GI-NENs, there were 83 cases (69.7%) of male and 36 cases (30.3%) of female. The age of patients ranged from 24 to 86 (median 61) years. Tumor locations included the stomach(n=70, 58.8%), duodenum(n=10, 8.4%), small intestine(n=2, 1.7%), appendix(n=3, 2.5%), colon(n=12, 10.1%), and rectum(n=22, 18.5%). The tumor diameter was 0.6 to 20 cm, the mean diameter was 5.4 cm, and the median diameter was 4 cm. There were 25 cases of G1 neuroendocrine tumor (NET), 7 cases of G2 NET and 87 cases of G3 neuroendocrine carcinoma (NEC). Among the 119 patients, 113 cases (95%) had complete follow-up, and the median follow-up was 75 (1 to 112) months. The 5-years overall survival rate was 58.4%. The survival rate of G1 NET, G2 NET and G3 NEC were 100%, 71.4%, 44.4%, and the difference was statistically significant (P=0.000). Univariate analysis showed that age ≥61 years (P=0.000), tumor located in the stomach, duodenum and colon (P=0.041), tumor size ≥4 cm (P=0.002), pathology classification of G3 NEC (P=0.000), late TNM staging (P=0.000) and blood PLR ≥133 (P=0.017) were associated with lower 5-year survival rate, but blood NLR level was not(P=0.263). Multivariate analysis showed that the patient age (HR=3.036, 95%CI: 1.548 to 5.956, P=0.001), the pathology classification(HR = 1.852, 95%CI:1.099 to 3.122, P=0.021), lymph node metastasis (HR=2.635, 95%CI:1.198 to 5.797, P=0.016) and distant metastasis (HR=2.685, 95%CI:1.383 to 5.214, P=0.004) were independent risk factors affecting the prognosis of patients, but the blood PLR level was not (HR=1.735, 95%CI: 0.947 to 3.176, P=0.074).</p><p><b>CONCLUSIONS</b>The malignant degree of GI-NEN is quite high, and the prognosis of patients is relatively poor. The age, pathological type and TNM staging are closely related to the prognosis of patients. Preoperative blood PLR may play a role in the prediction of prognosis, but preoperative blood NLR is not related with the prognosis of patients.</p>

The application of longitudinal stepped case teaching in the geriatrics education / 中华医学教育探索杂志

Case teaching method has been widely used in clinical medicine teaching.Because of the complicated diseases in elderly patients and the individual differences,it is difficult to achieve the goal of teaching only through several cases.Typical cases of different level are selected according to students' different learning stages and difficulty degree in longitudinal stepped case teaching.The students can gradually understand and master the theoretical knowledge through this method.In addition,their clinical thinking and the ability of solving practical problems can also be trained continuously.Preliminary practice shows that this teaching method is more suitable for the development of modern medical education and the needs of teaching.

Effect and mechanisms of aspirin on rat cardial fibroblast proliferation induced by aldosterone / 军事医学

Objective To investigate the effects of aspirin(aspi) on rat cardiac fibroblasts (CFs) proliferation induced by aldosterone(ald) and the underlying molecular mechanisms .Methods Primary CFs from 1-3 day neonatal rats were digested by 0.08%trypsin and then purified by differential adhesion .The rats were divided into four groups:control group, DMEM medium ( free calf serum ) , ald group [ DMEM medium ( free calf serum ) +ald 1 ×10 -8 mol/L ] , aspi group [DMEM medium (free calf serum)+ald 1 ×10 -8 mol/L+aspi 1.11 ×10 -6 mol/L] and spiro group [DMEM medium (free calf serum)+ald 1 ×10 -8 mol/L +spiro 1 ×10 -6 mol/L].The morphology of CFs was assayed by HE staining methods .MTT Methods were used to measure cell proliferation .Western blotting was used to determine protein expression of TGF-β-Smad 2,3,4.Results HE Staining results showed that compared with the control group , ald activated cell proliferation and increased the cell division phase significantly (P<0.01).Compared with ald group, aspi+ald as well as spiro+ald could reduce cell division significantly ( P<0 .05 ) .MTT assay showed that compared with control group , ald could significantly improve the metabolism of MTT in CF (P <0.01).Compared with ald group, aspi +ald as well as spiro+ald could reduce the metabolism of MTT (P<0.01).Western blotting revealed that the expression levels of TGF-β-Smad 2, 3, 4 in CF were significantly increased by the stimulation of ald but were significantly reduced in aspi +ald and spiro+ald groups compared with ald group (P<0.01).Conclusion Aspi can inhibit the proliferation of CFs induced by ald,possibly by down-regulating the expression of Smad 2, Smad3 and Smad4.

Retrospective clinical analysis of heterotopic pancreas misdiagnosed as gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To improve the differential diagnosis and treatment between heterotopic pancreas and gastrointestinal stromal tumor.</p><p><b>METHOD</b>Clinical and follow-up data of 14 cases who were diagnosed preoperatively as gastrointestinal stromal tumor whereas were confirmed as heterotopic pancreas in the gastrointestinal tract by postoperative pathological results in Renji Hospital from January 2007 to June 2013 were analyzed retrospectively.</p><p><b>RESULT</b>There were 9 males and 5 females, aged ranged from 26 to 69 years old. Eight patients had upper abdominal pain, 2 presented with intestinal obstruction, and 4 were incidentally found on routine health check-up. The lesions located at the stomach in 11 cases, at the duodenum in 1 case, and at the jejunum in 2 cases. All the patients underwent operation. Postoperative pathology confirmed the diagnosis of heterotopic pancreas. Among these lesions, 10 cases presented with co-existence of pancreatic acinus and duct as main component with smooth muscle and few gastric mucosa tissues, 3 cases was mainly the pancreatic acinus and 1 case mainly the pancreatic duct and smooth muscle.</p><p><b>CONCLUSIONS</b>Heterotopic pancreas may be misrocognized at gastrointestinal stromal tumors due to non-specific clinical manifestations and effective examination methods. Surgical procedure is the only one and the most effective treatment. Postoperative pathology examination is the most difinitive for differential diagnosis.</p>

A Study of the Intervention of Children with Bilateral Severe Hearing Loss in Countryside of China / 听力学及言语疾病杂志

Objective To investigate the effects of the intervention,rehabilitation and speech development of children with severe hearing loss in some rural areas.Methods 61 children,including 35 males and 26 females,were diagnosed as severe hearing loss with ABR and 40 Hz-AERP from June 2004 to July 2008.All the children failed hearing screening or visited the hospital as outpatients.The ages ranged from 2 to 72 months with the average age of 17.59 months.During telephone follow-up,the questionnaire was used to gather the data regarding the usage of hearing aids,hearing and speech rehabilitation,speech development,and communication abilities.Results 33 (54.10%) children were fitted with hearing aids,and 2 (3.28%) received cochlear implants,while 26(42.62 %) neither had hearing aids nor cochlear implants.10 cases with hearing aids also had speech training,whereas 23 children with hearing aids did not receive the training.2 cases with cochlear implants and 2 cases with hearing aids were found to have good speech development and communication ability,while 31 cases with hearing aids had delayed speech development.26 cases without any devices had to rely on sign language for their commumication.Conclusion Children in rural area with severe hearing loss experience greater speech and communication difficulties because many of them have no access to intervention and speech training.The results suggest that it would be very important to increase public awareness and educate parents to have their children wear hearing aids and receive speech training.

Study on multi-area universal newborn hearing screening in countryside of China / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the feasibility of universal newborn hearing screening in countryside in order to provide reliable evidence in launching this program all over the countryside of China. Method:Subjects were 12 638 infants who were born in 9 counties from Jan 2004 to Dec 2005. TEOAE was used for the fast hearing screening. Infants were screened on the 2-7 days after the birth. The re-screening was conducted in 4-6 weeks if failed in the initial screening,and follow-up were provided continually if they also failed in the re-screening. Result; Ten thouand eight hundred and forty-five of 12 638(85. 8%) were screened including 9 963(91. 9%) normal newborns and 882(8. 1%) newborns with high-risk. Seven thouand four hundred and fifty (68. 7%) newborns passed the initial screening, and 3 395 (31. 3%) people failed. One thouand seven hundred and ninty-three (14. 2%) infants were refused to be screened.Only 2 536 (74. 7%) were re-screened on time, and 859(25. 3%) did not receive re-screening. One hundred and twenty were failed in the re-screening or first screening, and 79 (65. 8%)of them received diagnostic assessment. Among the infants received diagnostic assessment, 6(7.6%)ca-ses were found to have profound hearing loss in both ears, 9(11. 4%)cases were found to be severe hearing loss(7 in both ears and 2 in single ear) , 11(13. 9%)cases were found to be moderate hearing loss (5 in both ear and 6 in single ear), 26 (32. 9%) were found to have slight hearing loss (11 in both ear and 15 in single ears), and 27 (34.2%) were normal. Fifty-two infants were diagnosed as hearing loss with a prevalence of congenital hearing loss(in binaural and monaural) of 0. 5%(52/10845)and a prevalence of bilateral hearing loss of 0. 3%(29/10845). A prevalence of congenital hearing loss was 0. 2% (22/9 963) in well infants and 3. 4% (30/882) in high risk infants. Among the 13 cases of children with severe and profound hearing loss in both ears children, 8(61. 5%)cases were fitted with hearing aids and 1 (7. 7%) case was implanted with cochlear implants. Conclusion:It is necessary and feasible to conduct hearing screening program in the rural area. However, the suitable model to perform the program in the countryside needs to be set up as soon as possible in order to get more poor infants to participate into the hearing screening program for free and increase the screening rate.

A noninvasive model to predict histological liver cirrhosis in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To construct a noninvasive model to predict histological liver cirrhosis in patients with chronic hepatitis B.</p><p><b>METHODS</b>275 patients with chronic hepatitis B were divided into a training group (206 cases) and a validation group (69 cases). The constituent ratios of patients in the fibrosis stages S0-S3, fibrosis stage S4 (early cirrhosis) and active cirrhosis stage were calculated according to the liver biopsy results. 30 noninvasive variables, including age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), spleen-platelet ratio index (SRPI) and age-spleen-platelet ratio index (ASPRI), were analyzed by univariate analysis and multivariate logistic regression. Variables that were significantly different between patients with and without cirrhosis were used to construct a noninvasive prediction model, and the model was then tested in the validation group.</p><p><b>RESULTS</b>(1) Of the 275 patients with chronic hepatitis B, 193 (70.2%) were in the fibrosis stages S0-S3, 42 (15.3%) in fibrosis stage S4, 40 (14.5%) in active cirrhosis stage. (2) There were 23 variables that are significantly different between patients with and without cirrhosis by univariate analysis. The 23 variables were further analyzed by multivariate logistic regression, and 4 independent factors, including international normalized ratio (INR), gamma glutamyltranspeptidase (GGT), ASPRI, hepatitis B e antigen (HBeAg) were used to construct a noninvasive prediction model. (3) By receiver operating characteristic curves (ROC) analysis, to discriminate patients in stages S0-S3 from patients in stage S4 and patients in active cirrhosis stage, the area under ROC (AUROC), cut-off value, sensitivity, specificity and accuracy of the model were 0.871, 0.458, 84.4%, 75.7%, and 79.7% respectively. To discriminate patients in active cirrhosis stage from patients in other stages, the AUROC, cut-off value, sensitivity, specificity and accuracy were 0.753, 0.526, 81.8%, 62.9%, and 67.4% respectively. There was no significant difference in AUROC between the training group and the validation group (P less than 0.05).</p><p><b>CONCLUSION</b>INR, GGT, ASPRI and HBeAg are associated with early cirrhosis and active cirrhosis. Our model can be used to predict early cirrhosis and active cirrhosis.</p>

Study on multi-area universal newborn hearing screening in countryside of China / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the feasibility of universal newborn hearing screening in countryside in order to provide reliable evidence in launching this program all over the countryside of China.@*METHOD@#Subjects were 12,638 infants who were born in 9 counties from Jan 2004 to Dec 2005. TEOAE was used for the fast hearing screening. Infants were screened on the 2-7 days after the birth. The re-screening was conducted in 4-6 weeks if failed in the initial screening, and follow-up were provided continually if they also failed in the re-screening.@*RESULT@#Ten thousand eight hundred and forty-five of 12,638 (85.8%) were screened including 9,963 (91.9%) normal newborns and 882 (8.1%) newborns with high-risk. Seven thousand four hundred and fifty (68.7%) newborns passed the initial screening, and 3,395 (31.3%) people failed. One thousand seven hundred and ninety-three (14.2%) infants were refused to be screened. Only 2,536 (74.7%) were re-screened on time, and 859 (25.3%) did not receive re-screening. One hundred and twenty were failed in the re-screening or first screening, and 79 (65.8%) of them received diagnostic assessment. Among the infants received diagnostic assessment, 6 (7.6%) cases were found to have profound hearing loss in both ears, 9 (11.4%) cases were found to be severe hearing loss (7 in both ears and 2 in single ear), 11 (13.9%) cases were found to be moderate hearing loss (5 in both ear and 6 in single ear), 26 (32.9%) were found to have slight hearing loss (11 in both ear and 15 in single ears), and 27 (34.2%) were normal. Fifty-two infants were diagnosed as hearing loss with a prevalence of congenital hearing loss (in binaural and monaural) of 0.5% (52/10845) and a prevalence of bilateral hearing loss of 0.3% (29/10845). A prevalence of congenital hearing loss was 0.2% (22/9,963) in well infants and 3.4% (30/882) in high risk infants. Among the 13 cases of children with severe and profound hearing loss in both ears children, 8 (61.5%) cases were fitted with hearing aids and 1 (7.7%) case was implanted with cochlear implants.@*CONCLUSION@#It is necessary and feasible to conduct hearing screening program in the rural area. However, the suitable model to perform the program in the countryside needs to be set up as soon as possible in order to get more poor infants to participate into the hearing screening program for free and increase the screening rate.