[Research and Application of Stem Cell-Based Therapy in Idiopathic Pulmonary Fibrosis: A Review].

Idiopathic pulmonary fibrosis (IPF) is a type of pulmonary disease that progresses acutely or slowly into irreversible pulmonary diseases, resulting in the end severe damages to patients' lung functions, as well as deaths. At present, the pathogenesis of pulmonary fibrosis is still not clear and there is no effective therapeutic measure available to control the progression of the disease. Research findings indicate that stem cells, being the origin of all cells of organisms, participate in the development of individuals at various stages and play an important role in repairing pulmonary tissue damage. Stem cells are attracting growing attention in the field of regenerative medicine, providing new ideas for treating IPF with transplanted stem cells. Herein, in order to better explore the potential applications of stem cell transplantation in treating IPF, we attempt to summarize preliminary studies of stem cell-mediated pulmonary remodeling after IPF, as well as cutting-edge clinical trials in stem cell-based IPF therapy.

64-Slice spiral double-low CT to evaluate the degree of stenosis and plaque composition in diagnosing coronary artery disease.

This study examined the application of 64-slice spiral double-low computed tomography (CT) to evaluate the degree of coronary artery stenosis. We examined 45 patients with coronary heart disease by 64-slice spiral double-low CT and coronary angiography (CAG) to determine CT accuracy in evaluating coronary artery stenosis. Imaging analysis from 64-slice spiral double-low CT identified 199 segments with coronary stenosis from 45 patients, including 46 segments with mild stenosis, 38 with moderate stenosis and 115 with severe stenosis or artery occlusion. CT analysis agreed with CAG on the identification of the degree of stenosis in 122 segments, with an overall accuracy of 61.3%. The accuracy for serious stenosis or occlusion was the highest at 69.6%. We also found a strong correlation between coronary plaque compositions and the degree of stenosis. Correspondence analysis showed that the presence of soft plaques closely correlated with severe stenosis, whereas mixed plaques closely correlated with moderate stenosis. Overall, 64-slice spiral double-low CT imaging can effectively assess the degree of coronary artery stenosis in patients with coronary heart disease and accurately detect plaque composition. Thus, 64-slice spiral double-low CT imaging can predict the risk of coronary heart disease and the degree of coronary artery stenosis, which is helpful for early diagnosis and treatment of coronary heart disease.

Simple nucleos(t)ides as HBV prophylaxis regime of post-liver transplantation: Six-year followed up.

A combination of nucleos(t)ides and hepatitis B immunoglobulin (HBIg) has been found to be effective for the prevention of hepatitis B viral (HBV) reinfection after liver transplantation (LT), but its administration is costly, and not always available. We report the case of a male, 33-year-old cirrhotic patient who has tested positive for serum HBsAg, and HBeAg, with 9.04 × 10(7) copies/mL of HBV DNA. He suffered from acute liver failure and was near death before undergoing emergency LT. No HBIg was available at the time, so only lamivudine was used. He routinely received immunosuppression medication. Serum HBV DNA and HBsAg still showed positive post-LT, and the graft re-infected. Hepatitis B flared three months later. Adefovir dipivoxil was added to the treatment, but in the 24(th) mo of treatment, the patient developed lamivudine resistance and a worsening of the hepatitis occurred shortly thereafter. The treatment combination was then changed to a double dosage of entecavir and the disease was gradually resolved. After 60-mo of post-LT nucleos(t)ide analogue therapy, anti-HBs seroconverted, and the antiviral was stopped. By the end of a 12-mo follow-up, the patient had achieved sustained recovery. In conclusion, the case seems to point to evidence that more potent and less resistant analogues like entecavir might fully replace HBIg as an HBV prophylaxis and treatment regimen.

[Imaging diagnosis of small hepatocellular carcinoma using ultrasound, contrast-enhanced ultrasound and multislice spiral CT].

OBJECTIVE: To evaluate the value of gray-scale ultrasound, contrast-enhanced ultrasound and multislice spiral CT in early and differential imaging diagnosis of small hepatocellular carcinoma (SHCC). METHODS: This study included 35 patients with space-occupying lesions in the liver identified by routine ultrasound examination. The hemodynamics of the patients was recorded during the arterial, portal and lag phases using contrast-enhanced ultrasound. The enhancement features of the 3 phases were observed using multislice spiral CT. All the cases were confirmed by pathological examinations. RESULTS: For SHCC diagnosis, gray-scale ultrasound, contrast-enhanced ultrasound and multislice spiral CT showed a sensitivity of 77.8%, 94.4%, and 100%, specificity of 88.2%, 100%, and 94.1%, positive predictive value of 87.5%, 100%, and 94.7%, negative predictive values 78.9%, 94.4%, and 100%, concordance rate of 82.9%, 97.1%, and 97.1% and Younden index of 0.66, 0.94, and 0.94, respectively. CONCLUSIONS: Contrast-enhanced ultrasound and multislice spiral CT have significantly greater diagnostic efficacy than gray-scale ultrasound in early and differential diagnosis of SHCC. But in some atypical cases, gray-scale ultrasound, contrast-enhanced ultrasound and multislice CT have to be combined to establish a diagnosis.

Model consisting of ultrasonographic and simple blood indexes accurately identify compensated hepatitis B cirrhosis.

BACKGROUND AND AIM: Several models for significant fibrosis or cirrhosis have been introduced for hepatitis C, but are seldom for hepatitis B. The present study retrospectively evaluates the relationship between ultrasonography, blood tests, and fibrosis stage, and constructs a model for predicting compensated cirrhosis. METHODS: A total of 653 patients with chronic hepatitis B who underwent liver biopsies, ultrasonographic scanning, and routine blood tests were retrospectively analyzed. The patients were divided into the model set and validation set. Blood tests and ultrasonographic indexes were analyzed statistically. An ultrasonographic scoring system consisting of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly was introduced. RESULTS: There were significant differences between cirrhosis and other fibrosis stages in ultrasonographic indexes of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly. Ultrasonographic scores were significantly different between F4 and other fibrosis, and significantly correlated with fibrosis stage. Apart from alanine aminotransferase and alkaline phosphatase, blood tests and patients' age were correlated with fibrosis, and were significantly different between patients with and without cirrhosis. The model for cirrhosis indexes consisting of ultrasonographic score, patient's age, and variables, including platelet, albumin, and bilirubin predicted cirrhosis with area under receiver-operator curve of 0.907 in the model set and 0.849 in the validation set. Using proper cut-off values, nearly 81% patients could be accurately assessed for the absence or presence of cirrhosis. CONCLUSION: The model consisting of ultrasonographic score, patients' age, blood variables of platelet, albumin, and bilirubin can identify hepatitis B cirrhosis with a high degree of accuracy. The application of this model would greatly reduce the number of biopsies.

[Factors influencing the success rate and stability of transient elastography for liver fibrosis evaluation].

OBJECTIVE: To investigate the factors influencing the success rate and stability of transient elastography(FibroScan)for assessment of liver fibrosis. METHODS: Liver stiffness was assessed using transient elastography in totally 637 subjects including healthy subjects, asymptomatic hepatitis B virus (HBV) carriers, patients with chronic hepatitis B and patients with HBV-related cirrhosis. Of these subjects, 302 received 2 examinations and totalling 939 examinations were performed. In each case, one operator performed 2 consecutive series of 10 validated measurements, or 2 operators performed a series of 10 validated measurements. The factors including gender, age, body mass index (BMI) and the state of diseases were analyzed for their association with the success of the examination. Intraclass correlation coefficient (ICC) was used to evaluate the reproducibility of the operation. RESULTS: Failure of the measurement occurred in 14 cases (2.2%), which was not associated with the age of the subjects and the state of diseases. The success rate of measurement decreased as the BMI increased (t=3.112, P=0.002), and was lower in female subjects (t=-2.193, P=0.029). The intra- and inter-operator stability of liver stiffness measurement was satisfactory, with ICC of 0.970 and 0.847, respectively. But for healthy subjects and asymptomatic HBV carriers, the stability was lower, with ICC of 0.736 and 0.639, respectively. Liver stiffness in patients with liver cirrhosis was positively correlated to complications and Child-Turcotte-Pugh (CTP) score. CONCLUSION: Liver stiffness measurement has high stability with FibroScan, and high BMI could lower success rate of the measurement. Liver stiffness as measured by FibroScan allows prediction of the liver function and presence of complications in patients with liver cirrhosis.

[Study of the relapse of patients with chronic hepatitis B undergoing first and repeated recombinant interferon-alpha therapy during long-term follow up].

OBJECTIVE: To investigate the relapse of patients with chronic hepatitis B (CHB) undergoing first and repeated recombinant interferon-alpha (rIFN-alpha) therapy during long-term follow up. METHOD: Five hundred and twenty three patients with chronic hepatitis B including 403 hepatitis B e-antigen (HBeAg) positive patients and 120 HBeAg negative ones were treated with 5MU recombinant interferon-alpha 1b (rIFN-alpha1b) subcutaneously thrice weekly for 6 - 25 (median 10) months. For each patient, serum alanine aminotransferase (ALT) was measured biochemically and serum HBV DNA level was detected by fluorescent-quantitative PCR, HBeAg with enzyme immunoassay every 1 - 3 month during therapy and every 3 - 6 month during the follow up period. Some of the individuals who relapsed during the follow-up period were treated with interferon-alpha repeatedly. RESULTS: Ratios of early response to interferon-alpha were similar in HBeAg positive patients (55.8%, 225/403), and HBeAg negative patients (64.2%, 77/120) at the end of naive treatment (chi(2) = 2.633, P = 0.105). 39.4% (119/302) of early responders relapsed during 39 +/- 22-month follow up, and relapse rates in HBeAg negative group (55.8%, 43/77) were higher than those in HBeAg positive group (33.8%, 76/225) at the end of follow up (chi(2) = 19.335, P = 0.000). Divided the follow-up period into six fragments as 1 - 12 months, 13 - 24 months, 25 - 36 months, 37 - 48 months, 48 - 60 months and > or = 61 months, we found that the differences of relapse incidence were significant (chi(2) = 73.518, df = 5, P = 0.000), and accumulative relapse rates were significant too (chi(2) = 32.167, df = 5, P = 0.000) in all follow-up periods. Constituent ratios of HBeAg in relapsed patients of every follow-up period were similar. 57 relapsed individuals (25 in HBeAg positive group and 32 in HBeAg negative group) were retreated with interferon-alpha, and complete response were achieved in all cases at the end of repeated therapy. The relapse rates in HBeAg positive group (52.0%, 13/25) were higher than in HBeAg negative group (21.9%, 7/32) during the follow-up period after the end of retreatment (chi(2) = 5.592, P = 0.018). CONCLUSION: Rates of early response to interferon-alpha therapy were similar in HBeAg positive and HBeAg negative patients at the end of nave treatment, and relapse rates in HBeAg negative group were higher than in HBeAg positive group during long term follow-up. Combined response was achieved in all relapse cases received repeated interferon-alpha therapy at the end of retreatment. The relapse rates in HBeAg positive group were higher than in HBeAg negative group during the follow-up period after repeated therapy.

[Factors related to chronic hepatitis B relapse after interferon-alpha treatment: a follow-up study].

OBJECTIVE: To investigate the related to relapse of chronic hepatitis B (CHB) after recombinant interferon-alpha (rIFN-alpha) treatment. METHODS: This investigation involved 523 pathologically confirmed CHB patients including 403 HBeAg-positive and 120 HBeAg-negative patients, who were treated with 5 MU rIFN-alpha subcutaneously thrice a week for 6-25 months. For each patient, serum alanine aminotransferase (ALT) was measured biochemically, serum HBV DNA level detected with quantitative fluorescent PCR, and HBeAg level with enzyme immuoassay every 1-3 months during therapy and every 3-6 months during the follow-up period. RESULTS: Early response to rIFN-alpha treatment was observed in 302 (57.7%) patients at the end of treatment, among whom 39.4% (119/302) suffered relapse during the follow-up for 39.2-/+21.5 months. Age, HBeAg status before treatment, and follow-up duration were the predictive factors for post-treatment relapse. The mean age of patients with CHB relapse was significantly higher than that of the sustained responders (P<0.001), and the relapse rates in HBeAg-negative group (55.8%, 43/77) were significantly higher than that in HBeAg-positive group (33.8%, 76/225) at the end of follow up (P<0.001). The relapse rate and accumulative relapse rates at each year during the follow-up (for 5 years as the longest) differed significantly (P<0.001, P=0.000), but the accumulative relapse rates differed little between the years after the initial 2 of the follow-up (P=0.670). The relapse was not related to the patient's gender, pretreatment serum ALT, HBV DNA, grade of liver inflammation, stage of liver fibrosis, or duration of treatment. In HBeAg-positive patients, however, the mean HBV DNA was significantly higher in relapse group than in sustained response group (P=0.017). CONCLUSION: Age, pretreatment HBeAg status, and follow-up duration are independent predictive factors for post-treatment CHB relapse. In HBeAg positive patients, pretreatment serum HBV DNA is also one of the risk factors for relapse.

[Viral breakthrough and neutralizing anti-interferon antibody production in chronic hepatitis B patients treated with recombinant interferon-alpha].

OBJECTIVE: To investigate the relationship of virological breakthrough and production of neutralizing anti-interferon antibody (NAb) in chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha). METHOD: Four hundred eighty-five patients with histological proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha1b) thrice weekly for 6-37 months (median 10). Serum HBV DNA, HBeAg and NAb levels of the patients were detected by fluorescent-quantitative PCR, enzymoimmunoassay and antiviral neutralizing biological assay respectively during the therapy. RESULTS: Virological breakthrough occurred in 66 patients (13.6%), and NAb was found in 98 patients (20.2%) of the total 485 patients. The rate of NAb positivity was higher in patients with viral breakthrough than those without it (68.2%, 45/66, vs 12.6%, 53/419, chi(2)=109.06, P < 0.01), and viral breakthrough occurred more in patients with positive NAb than with negative NAb (45.9%, 45/98, vs 5.4%, 21/387, chi(2)=109.06, P < 0.01). The time of the viral breakthrough occurrence and the time of NAb production had a significant correlation (P < 0.01). The occurrence of viral breakthrough was also influenced by the age of patients (P < 0.05) and HBeAg status (P < 0.01) before they were treated. CONCLUSION: Viral breakthrough occurred in 13.6% of our 485 chronic hepatitis B patients treated with recombinant interferon-alpha. Their viral breakthrough and production of NAb production had a significant correlation.

[A study of the causes of poor antiviral responses in male chronic hepatitis B patients treated with recombinant interferon-alpha].

OBJECTIVE: To study the causes of poorer antiviral response to neutralizing anti-interferon-alpha antibodies (NA) in male chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha). METHODS: Two hundred sixty-nine patients (198 males and 71 females) with histologically proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha 1b) subcutaneously thrice weekly for 6-37 (median 10.0) months. For each patient, serum HBV DNA levels were detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay, and NA with an antiviral neutralizing biological assay during therapy. RESULTS: NA was found in 70 (35.4%) of the 198 males and in 15 (21.1%) of the 71 females during treatment (x2 = 4.894, P = 0.027). At the end of treatment combined-response was achieved in 21 (24.7%) of the 85 NA-positive patients and in 100 (54.3%) of the 184 NA-negative cases (x2 = 20.642). Stratification analysis by NA showed that combined-response rate was significantly lower in males than in females (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among NA-positive patients while it was similar in males and in females (50.8%, 65/128, vs. 62.5%, 35/56, x2 = 2.156) among NA-negative patients. In stratification analysis by gender, it was significantly lower in NA-positive patients than in NA-negative ones (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among males but there was no significant difference between combined-response rates among females. CONCLUSION: The poorer antiviral response to recombinant interferon-alpha in male chronic hepatitis B patients than in female patients is related to the neutralizing anti-interferon antibodies.

[Efficacy of interferon-alpha therapy for HBeAg-negative chronic hepatitis B and its influencing factors].

OBJECTIVE: To investigate the efficacy of interferon-alpha (IFN-alpha) therapy for HBeAg-negative chronic hepatitis B. METHODS: Sixty-five Chinese HBeAg-negative chronic hepatitis B patients were treated with 5 MU recombinant rIFN-alpha 1b subcutaneously thrice weekly for 5 to 24 months, followed by 12 months of treatment-free follow-up; one hundred and eighty-eight Chinese HBeAg-positive patients served as controls. For each patient, serum alanine transaminase (ALT) was measured biochemically and serum HBV DNA level was detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay every 1 to 3 months during therapy and during the follow-up period. HBeAg loss (only for HBeAg-positive cases), HBV DNA undetectable, and ALT normalization: the three together were considered a combined response. RESULTS: Rates of combined response were similar in HBeAg-negative patients (58.5%, 38/65) or HBeAg-positive ones at the end of treatment (weighted chi square test, chi2 = 1.878, P<0.05), but were higher at the end of the follow-up period in the HBeAg-negative cases (75.4%, 49/65) (weighted chi square test, chi2 = 4.796, P<0.05). Furthermore, relapse rates at the end of the follow-up period, were also similar in HBeAg-negative patients (15.8%, 6/38) or HBeAg positive (chi2 = 0.205, P>0.05). Combined response was achieved at a median of 6.0 months (2-16 months) of treatment course in HBeAg-negative patients while at a median of 6.0 months (1-22 months) in HBeAg-positive cases (Z = -0.186, P>0.05, by the Wilcoxon rank sum test). The only factor predictive of combined response, by binary logistic regression analysis, was inflammatory activity in the liver biopsy. Gender, age, baseline ALT level, baseline HBV DNA level, and anti-HBe were not predictive factors. CONCLUSION: Interferon-alpha therapy induces a similar primary and sustained response in HBeAg-negative and in HBeAg-positive chronic hepatitis B patients.

[Evaluation of non-invasive indices for liver histology in patients with chronic hepatitis B].

OBJECTIVE: To assess the correlation of routine blood and serum biochemical indices with liver histology, and identify the sensitive non-invasive ones indicative of liver inflammation and fibrosis in patients with chronic hepatitis B. METHODS: A total of 252 patients were enrolled in this retrospective analysis. The indices including the patients' age, gender, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, globulin, total bilirubin, prothrombin time (PT) and its activity (PTA), WBC, and platelet count were analyzed statistically. RESULTS: The status of liver inflammation was correlated to patients' routine blood indices (P<0.05). Serum AST, total bilirubin, WBC, and platelet count was related significantly to the degree of liver inflammation, but serum ALT and AST alone did not describe exactly the degree of liver inflammation. The status of liver fibrosis was independent of patients' serum ALT, but correlated to other routine blood indices (P<0.05). The patients' age, serum AST, total bilirubin and platelet count had significant relation to the stage of liver fibrosis, and the age, blood PT, total bilirubin and platelet count were significant relevant indices for early liver cirrhosis, and their sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 31.5%, 94.4%, 60.7%, 83.3% and 80.7%, respectively. CONCLUSIONS: Single examination of serum ALT and AST does not help much to predict the status of liver test in patients with chronic hepatitis B. Serum AST, total bilirubin, WBC and platelet count are associated with the degree of liver inflammation. The patients' age, serum total bilirubin, AST and platelet count are relevant indices for liver fibrosis, and patients' age, serum total bilirubin, PT, and platelet count provide valuable assistance in confirmation of early liver cirrhosis with high specificity, but not so for screening purpose.

[Epidemiological investigation of nosocomial infection of SARS in medical staff of a hospital].

OBJECTIVE: To investigate the epidemiological features of nosocomial infection of severe acute respiratory syndrome (SARS) in the medical staff of a hospital. METHODS: The medical staff associated with nosocomial infection of SARS in a hospital were investigated with standard procedures of epidemiological survey. RESULTS: The source of SARS infection was identified as the husband of a tumor patient who received chemotherapy in the Department of Oncology, during which they maintained intimate contact for at least two weeks when the husband had typical symptoms of SARS. The tumor patient had no any signs of SARS before her death. The mean latent period of SARS was 12.6 days in the 8 nurses transferred temporarily from other departments to assist in the management of the tumor patient. All 57 persons with close contact with the 12 medical staff suffering SARS in the latent period or with one having early-stage SARS did not show any signs of SARS during one month for observation in isolation. CONCLUSION: SARS patients may have no or very limited infectivity during the latent period. Infection of SARS might be concerned with the intensity and persistence of contact with the infectious sources. The pathogenesis of SARS might involve the immune status of the potential patients, and immunodeficient individuals are at the risk of becoming asymptomatic carriers of SARS virus and the infectious sources.

[Screening and evaluation of non-invasive diagnosis markers for compensated liver cirrhosis in patients with chronic hepatitis B].

OBJECTIVE: To evaluate the diagnostic value of liver fibrosis markers and ultrasonic examination for determining compensated liver cirrhosis in patients with chronic hepatitis B, and screen applicable non-invasive diagnostic marker for compensated liver cirrhosis. METHODS: Serum hyaluronic acid (HA), Type III procollagen (PCIII), laminin (LN) and Type IV collagen (CIV) were measured from 350 patients with chronic hepatitis B, who were also detected with liver biopsy and ultrasonography. To determine the cut-off value of every serum liver fibrosis marker for diagnosing compensated liver cirrhosis, data was analysed with clinical epidemiology methods. Then evaluated and compared all the markers. RESULTS: 85 out of 350 patients were diagnosed as compensated liver cirrhosis by liver biopsy, and 81 had liver cirrhosis images by ultrasonic examination. HA achieved the biggest area under the ROC curve. The cut-off values with best sensitivity and accuracy of HA, PCIII, LN and CIV were 154.35 microg/L, 198.44 microg/L, 137.58 microg/L and 100.80 microg/L respectively. The related diagnostic sensitivities of HA, PCIII, LN and CIV were 82.4%, 63.5%, 57.3% and 70.6%, specificities were 79.3%, 54.0%, 56.8%, 68.3%, and accuracies were 80.0%, 56.3%, 56.9%, 68.9%, respectively. Parallel tests could increase the diagnostic sensitivity, but decreased specificity and accuracy accordingly. Compared with other non-invasive diagnostic methods, HA was the best marker (mu > or =1.814, P<0.05). The level of HA at 119.17 microg/L was suitable for determining compensated cirrhosis, with a 87.1% sensitivity, 67.6% specificity, 72.3% accuracy, 46.25% positive predictive value and 94.7% negative predictive value. CONCLUSION: Among the non-invasive serum diagnostic markers for liver fibrosis and ultrasonic examination for cirrhosis image, HA is the best marker for diagnosing compensated liver cirrhosis.