1.The Role of Impulsivity in Cognitive Impairment in Manic Episodes of Bipolar Ⅰ Disorder
Jie LI ; Mi-liang SHI ; Gen-xiang PEI ; Xu-dong LI ; Ai-hong ZHANG
Progress in Modern Biomedicine 2025;25(15):2511-2516,2529
Objective:To observe the role of impulsivity in cognitive impairment in manic episodes of bipolar Ⅰ disorder(BPDTI)patients.Methods:180 cases of patients with BPDTI manic episodes admitted to our hospital from February 2024 to December 2024 were selected as the manic group,and another 180 cases of volunteers who were psychologically tested as normal during the same period were selected as the healthy group.The impulse Barratt-11 scale(BIS-11)and the MATRICS Consensus Cognitive Test(MCCB)were used to investigate and evaluate impulsivity and cognitive function,and correlation analysis and risk factor analysis were conducted.Results:In the BIS-11 scale,there was no statistically significant difference between the two groups in the unplanned factor(P>0.05),but there were significant differences compared between the two groups in cognitive,motor factors,and total score(P<0.05).The MCCB scores of the manic group in information processing speed,working memory,word learning,visual learning,social cognition,reasoning and problem solving,and attention vigilance were significantly lower than those of the healthy group(P<0.05).The relationship between BIS-11 total score and cognitive impulsivity factor and MCCB total score and word learning showed there were negative correlation(P<0.05);The exercise factor in the BIS-11 scale were negatively correlated with the MCCB total score and working memory factor(P<0.05);The unplanned factor in the BIS-11 scale showed there were negative correlation with the MCCB total score,word learning(P<0.05),and information processing speed.BIS-11,the number of years of education was an influencing factor for BPDTI mania(P<0.05).Conclusion:BPDTI mania patients had high impulsivity and cognitive impairment,high impulsivity and number of years of education were influencing factors for mania,high impulsivity affected cognitive function through corresponding brain regions,aggravating the condition.
2.The Role of Impulsivity in Cognitive Impairment in Manic Episodes of Bipolar Ⅰ Disorder
Jie LI ; Mi-liang SHI ; Gen-xiang PEI ; Xu-dong LI ; Ai-hong ZHANG
Progress in Modern Biomedicine 2025;25(15):2511-2516,2529
Objective:To observe the role of impulsivity in cognitive impairment in manic episodes of bipolar Ⅰ disorder(BPDTI)patients.Methods:180 cases of patients with BPDTI manic episodes admitted to our hospital from February 2024 to December 2024 were selected as the manic group,and another 180 cases of volunteers who were psychologically tested as normal during the same period were selected as the healthy group.The impulse Barratt-11 scale(BIS-11)and the MATRICS Consensus Cognitive Test(MCCB)were used to investigate and evaluate impulsivity and cognitive function,and correlation analysis and risk factor analysis were conducted.Results:In the BIS-11 scale,there was no statistically significant difference between the two groups in the unplanned factor(P>0.05),but there were significant differences compared between the two groups in cognitive,motor factors,and total score(P<0.05).The MCCB scores of the manic group in information processing speed,working memory,word learning,visual learning,social cognition,reasoning and problem solving,and attention vigilance were significantly lower than those of the healthy group(P<0.05).The relationship between BIS-11 total score and cognitive impulsivity factor and MCCB total score and word learning showed there were negative correlation(P<0.05);The exercise factor in the BIS-11 scale were negatively correlated with the MCCB total score and working memory factor(P<0.05);The unplanned factor in the BIS-11 scale showed there were negative correlation with the MCCB total score,word learning(P<0.05),and information processing speed.BIS-11,the number of years of education was an influencing factor for BPDTI mania(P<0.05).Conclusion:BPDTI mania patients had high impulsivity and cognitive impairment,high impulsivity and number of years of education were influencing factors for mania,high impulsivity affected cognitive function through corresponding brain regions,aggravating the condition.
3.Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study.
Huai ZHANG ; Rafael S RIOS ; Jerome BOURSIER ; Rodolphe ANTY ; Wah-Kheong CHAN ; Jacob GEORGE ; Yusuf YILMAZ ; Vincent Wai-Sun WONG ; Jiangao FAN ; Jean-François DUFOUR ; George PAPATHEODORIDIS ; Li CHEN ; Jörn M SCHATTENBERG ; Junping SHI ; Liang XU ; Grace Lai-Hung WONG ; Naomi F LANGE ; Margarita PAPATHEODORIDI ; Yuqiang MI ; Yujie ZHOU ; Christopher D BYRNE ; Giovanni TARGHER ; Gong FENG ; Minghua ZHENG
Chinese Medical Journal 2023;136(3):341-350
BACKGROUND:
Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.
METHODS:
Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL).
RESULTS:
A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P < 0.001, P = 0.026 and P = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal.
CONCLUSION
This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans
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Non-alcoholic Fatty Liver Disease/diagnosis*
;
Keratin-18
;
Biomarkers
;
Biopsy
;
Hepatocytes/pathology*
;
Apoptosis
;
Liver/pathology*
4.Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research.
Wei XU ; Shu Hua YI ; Ru FENG ; Xin WANG ; Jie JIN ; Jian Qing MI ; Kai Yang DING ; Wei YANG ; Ting NIU ; Shao Yuan WANG ; Ke Shu ZHOU ; Hong Ling PENG ; Liang HUANG ; Li Hong LIU ; Jun MA ; Jun LUO ; Li Ping SU ; Ou BAI ; Lin LIU ; Fei LI ; Peng Cheng HE ; Yun ZENG ; Da GAO ; Ming JIANG ; Ji Shi WANG ; Hong Xia YAO ; Lu Gui QIU ; Jian Yong LI
Chinese Journal of Hematology 2023;44(5):380-387
Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female
;
Humans
;
Male
;
Aged
;
Middle Aged
;
Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy*
;
Prognosis
;
Lymphoma, B-Cell
;
Immunohistochemistry
;
Immunoglobulin Heavy Chains/therapeutic use*
5.Factors associated with significant liver fibrosis in chronic hepatitis B patients with non-alcoholic fatty liver disease
Rui ZENG ; Liang XU ; Ping MA ; Xiaowen GONG ; Ping LI ; Feinan LYU ; Youfei ZHAO ; Ruifang SHI ; Yonggang LIU ; Yuqiang MI
Chinese Journal of Infectious Diseases 2020;38(7):426-431
Objective:To investigate the influencing factors of significant liver fibrosis in patients with chronic hepatitis B (CHB) concurrent with non-alcoholic fatty liver disease (NAFLD).Methods:Those who underwent liver pathological examination and confirmed diagnosis of CHB and NAFLD in Tianjin Second People′s Hospital from August 2014 to September 2017 were enrolled. Data regarding their demographic information, laboratory tests results, and liver pathology results were analyzed. The latter results were used to categorize the patients either in non-significant liver fibrosis group (Metavir stage
6.Study of reactive oxygen species and adiponectin for chronic HBV infection combined with nonalcoholic fatty liver diseases
Liang XU ; Yan ZHONG ; Shuting SU ; Yonggang LIU ; Feinan LYU ; Xiaoli ZHOU ; Jinqing REN ; Ping LI ; Ruifang SHI ; Yong JIANG ; Jiangao FAN ; Yuqiang MI
Chinese Journal of Hepatology 2020;28(3):247-253
Objective:To investigate the application value of reactive oxygen species (ROS) and adiponectin (ADPN) in the judgment of liver inflammation in chronic hepatitis B virus infection combined with nonalcoholic fatty liver disease (NAFLD).Methods:A total of 159 cases with NAFLD (21 cases), chronic hepatitis B virus infection (57 cases), and chronic hepatitis B virus infection combined with NAFLD (81 cases) were collected between June 2016 to December 2018, and the visited patients diagnosis were confirmed by histopathological examination of the liver. ROS and ADPN level retained in serum was determined by enzyme-linked immunosorbent assay. Histopathological examination of liver tissue was used as the gold standard to discuss the diagnostic value of the serum in patients with chronic hepatitis B virus infection combined with NAFLD for the occurrence of nonalcoholic steatohepatitis. One-way analysis of variance was used for the comparison among multiple groups, and LSD-t test was used for pairwise comparison between groups. Measurement data for non-normal distributions were expressed as M (P25, P75). Comparisons between groups were performed using the Mann-Whitney U or Kruskal-Wallis H test. Chi-square test was used to compare the count data between groups. Correlation analysis was performed using Spearman correlation analysis. Histopathological grouping of liver tissue was used as the gold standard, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the regression formula.Results:(1) In patients with chronic hepatitis B virus infection combined with NAFLD, the levels of ROS in the non-hepatic steatosis group and the mild hepatic steatosis group were significantly lower than those in the moderate and severe hepatic steatosis group, while the ADPN level in the non-hepatic steatosis group was significantly higher than liver steatosis group, P < 0.05. (2) The results of correlation analysis showed that ROS was significantly correlated with NAS score, change in the degree of fatty liver and lobular inflammation (all P < 0.05).There was a significant negative correlation between ADPN and the change in the degree of fatty liver ( P < 0.05). (3) Logistic regression analysis results showed that the diagnostic formula for chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis was 0.02 × controlled attenuation index + 0.584 × white blood cells/10 9 + 0.587 × ROS-10.982. The area under receiver operating characteristic curve of the subject was = 0.896. The sensitivity, specificity, positive and negative predictive value were 97.1%, 71.2%, 64.2%, and 97.9%. Conclusion:ADPN and ROS have certain reference value in differentiating the change in the degree of fatty liver and inflammation in chronic hepatitis B virus infection combined with NAFLD and the diagnostic formula has higher application value in the diagnosis and exclusion of chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis.
7.Clinical trial of nalbuphine hydrochloride injection on analgesia after cesarean section and its preventive effect on postpartum depression
Dun-Liang WANG ; Mi-Qun WANG ; Rong SHEN ; Jian-Wen SHI ; Peng ZHANG
The Chinese Journal of Clinical Pharmacology 2017;33(9):782-785
Objective To observe the clinical efficacy and safety of nalbuphine hydrochloride injection on cesarean section analgesia and its preventive effect on postpartum depression.Methods A total of 400 term pregnancy maternal with cesarean section were randomly divided into groups A,B,C,D with 100 cases per group.Group A was treated with sufentanil 100 μg.Groups B,C,D were treated with hydrochloric nalbuphine 1.5,2.0 and 2.5 mg · kg-1,respectively.Four groups received patient-controlled intravenous analgesia.The visual analogue scale (VAS) and Ramsay sedation scores (RSS) of 6,12,24 h after operation,depression status and adverse drug reactions were compared between four groups.Results 6,12,24 h after operation,in group A,VAS were (3.21 ± 0.44),(3.15 ± 0.49),(2.06 ± 0.49) points,RSS were (2.08 ± 0.37),(2.05 ± 0.35),(1.85 ± 0.23) points;in group B,VASwere (2.17±0.35),(2.00±0.38),(1.45 ± 0.38) points,RSS were (2.01 ±0.19),(1.91±0.21),(1.72 ± 0.18) points;in group C,VAS were (2.08 ± 0.22),(1.53 ± 0.26),(0.75 ± 0.13)points,RSS were (1.71±0.15),(1.75±0.12),(1.46±0.15)points;in group D,VAS were (2.10±0.21),(1.52 ±0.21),(0.72 ± 0.11) points,RSS were (1.64 ± 0.22),(1.62 ± 0.15),(1.43 ± 0.21) points,there were significant differences in VAS score and RSS score at different times between groups C,D and groups A,B (P < 0.05).3 d postpartum,the depression rates in groups A,B,C,D were 35.00% (35/100 cases),27.00% (27/100 cases),12.00% (12/100 cases),26.00% (26/100 cases),with significant differences between group C and groups A,B,D (P < 0.05).The adverse drug reactions in group A were heart rate,vomiting,diarrhea and rash,which in group B and C were rapid heartbeat,nausea,vomiting and urinary retention,in group D were rapid heartbeat,nausea,vomiting,diarrhea and rash.The incidences of adverse drug reactions were 14.00%,10.00%,11.00%,21.00%,with significant differences between group D and groups A,B,C (P < 0.05).Conclusion Nalbuphine 2.0 mg · kg-1 has a definitive clinical efficacy on analgesic and sedative after cesarean section,with low postpartum depression rate and adverse reactions rate.
8.Value of controlled attenuation parameter in diagnosis of fatty liver using FibroScan.
Liang XU ; Ping LI ; Wei LU ; Qiyu SHI ; Ruifang SHI ; Xiaoying ZHANG ; Yonggang LIU ; Qiujing WANG ; Jangao FAN ; Yuqiang MI
Chinese Journal of Hepatology 2016;24(2):108-113
OBJECTIVETo investigate the value of controlled attenuation parameter (CAP) in the diagnosis of fatty liver using FibroScan in patients with chronic liver disease (CLD).
METHODSA prospective cohort study was performed for the patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) who underwent liver pathological examination followed by CAP measurement within 1 week in The Second People's Hospital of Tianjin from February 2013 to May 2014. According to related guidelines, hepatocyte steatosis was classified as S0: <5%, S1: 5%-33%, S2: 34%-66%, or S3: ≥67%. The receiver operating characteristic (ROC) curves were plotted with positive results as the diagnostic criteria, and the optimal cut-off values were determined at the maximum Youden index. Single linear regression and multiple stepwise regression were applied to analyze the influencing factors for CAP.
RESULTSA total of 427 patients were enrolled, consisting of 19 patients (4.4%) with NAFLD, 383 (89.7%) with CHB, and 25 (5.9%) with CHC. The optimal cut-off values for CAP in the diagnosis of steatosis ≥5%, ≥34%, and ≥67% were 230 dB/m, 252 dB/m, and 283 dB/m, respectively, and the areas under the ROC curve were 0.803, 0.942, and 0.938, respectively (Z = 14.194, 28.385, and 16.486, respectively, all P < 0.01). CAP differentiated S0 from S1, S1 from S2, S0 from S2, S0 from S3, and S1 from S3 (Z = 10.109, 10.224, 47.81, 29.917, and 10.999, all P < 0.01), but was not able to differentiate S2 from S3 (Z = 0.656, P = 0.5116). The single linear regression and multiple stepwise regression analyses showed that only body mass index (BMI; B = 4.001, P < 0.01) and hepatic steatosis (B = 33.015, P = 0.000) were correlated with CAP. The coincidence rates between CAP and liver pathological diagnosis were 77.4%, 81.0%, and 96.2% for S0, S3, and ≥S2, respectively.
CONCLUSIONCAP has a good value in the diagnosis of fatty liver in CLD patients, and can well differentiate between all stages of fatty liver except S2 and S3. CAP is influenced by BMI, but is not found to be associated with liver fibrosis, inflammation, liver stiffness measurement, and etiology.
Area Under Curve ; Biopsy ; Body Mass Index ; Cell Differentiation ; Elasticity Imaging Techniques ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Inflammation ; complications ; Linear Models ; Liver Cirrhosis ; complications ; Multivariate Analysis ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; Prospective Studies ; ROC Curve
9.Effect of Acupuncture Combined Physical Training and Relearning on Stroke Rehabilitation: a Multi-center Randomized Controlled Clinical Study.
Xiao-liang WU ; Zhong-ping MI ; He-sheng WANG ; Dao-ming XU ; Li-xia PEI ; Jing LIU ; Wen SHI ; Wei-chao PAN ; Li-xia ZHANG ; Li-ping CHEN ; Yin ZHANG ; Jian-hua SUN
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(5):549-554
OBJECTIVETo observe the effect of acupuncture combined physical training and relearning on stroke patients.
METHODSA multi-center, randomized controlled trial design was adopted. A total of 364 stroke patients were recruited and randomly assigned to the experimental group (184 cases) and the control group (180 cases). Patients in the experimental group received acupuncture combined with physical training and relearning, while those in the control group only received physical training and relearning. All received four weeks of treatment. Effects on Fugl-Meyer motor function, neurological impairment, activities of daily living difference were compared before treatment, after treatment, 2 and 5 months after follow-ups between the two groups.
RESULTSTotally 353 patients completed this trial, 179 in the experimental group and 174 in the control group. (1) compared with before treatment, brief Fugl-Meyer motor functions scores and FIM scored obviously increased, and scores for neurological impairment obviously decreased in the two group. Besides, the increment of brief Fugl-Meyer motor functions scores and FIM scores was obviously higher in the experimental group than in the control group at month 2 and 5 of follow-ups; scores for neurological impairment was obviously lower in the experimental group than in the control group. The increment of FIM scores was obviously higher in the experimental group than in the control group at month 5 of follow-ups (P < 0.05, P < 0.01). (2) There was statistical difference in inter-group comparison of total Fugl-Meyer motor functions scores and FIM scores, or scores for neurological impairment (P < 0.01). The improvement of Fugl-Meyer motor functions grading and neurological impairment grading was obviously superior in the experimental group at month 2 and 5 of follow-ups. The distribution of FIM grading was also better in the experimental group at month 5 of follow-ups (P < 0.05, P < 0. 01).
CONCLUSIONSBoth acupuncture combined exercise training and relearning and physical training and relearning could effectively promote the rehabilitation of stroke patients, reduce their neurological impairment degrees, improve motor functions and independent capacities. Better long-term efficacy could be obtained by acupuncture combined exercise training and relearning.
Activities of Daily Living ; Acupuncture Therapy ; Biomedical Research ; Exercise Therapy ; Humans ; Research Design ; Stroke Rehabilitation ; Treatment Outcome
10.Impact of liver steatosis on the curative effect of pegylated interferon-alpha-2a in patients with chronic hepatitis B.
Liang XU ; Ping LI ; Qiyu SHI ; Yuqiang MI
Chinese Journal of Hepatology 2015;23(2):99-102
OBJECTIVETo investigate the impact of hepatic steatosis on virologic response to treatment with pegylated interferon-alpha-2a (PEG-IFNα-2a) in chronic hepatitis B (CHB) patients.
METHODSWe retrospectively analyzed 50 biopsy-proven cases of CHB in patients who had been administered a 48-week course of PEG-IFNα-2a in our hospital between 2005 and 2009. The patients were stratified according to presence of steatosis confirmed by pathological findings, with 28 in the non-steatosis group and 22 in the steatosis grouP(21 with mild steatosis,and 1 with moderate steatosis).
RESULTSfrom blood routine test,hepatic and renal function tests, fasting blood glucose test, thyroid function test and blood lipid test were collected for analysis, as were results from hepatitis B viral load test and detection of hepatitis B virus (HBV) markers and autoantibodies. The efficacy of antiviral treatment and side effects were compared between the stratified groups by statistically comparing the results from before and after the 48 weeks of treatment.
RESULTSAt the end of treatment, the non-steatosis group had 42.9% of patients with undetectable HBV-DNA ( less than 500 copies/ml), a hepatitis B e antigen (HBeAg) seroconversion rate of 31.6% and a complete response rate of 39.3%. The steatosis group had a lower rate of patients with undetectable HBV-DNA (40.9%) and higher rates of HBeAg seroconversion (33.3%) and complete response (40.9%), but none of the differences reached the threshold for statistical significance (x2=0.012, 0.019, 0.014 and P=0.560,0.600,0.568 respectively). Both groups showed significant increases in triglyceride levels after treatment (steatosis group:t =-2.164, P=0.040; non-steatosis group:t =-2.863, P=0.009), and there was a significant difference between the two groups (t=2.41, P=0.020).
CONCLUSIONOur study did not show that mild hepatic steatosis affected the efficiency of a 48-week course of PEG-IFNα-2a treatment for patients with CHB.
Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Fatty Liver ; pathology ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; drug therapy ; pathology ; Humans ; Interferon-alpha ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Retrospective Studies

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