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Time-reversal imaging struggles to detect plate-like structures due to interference from Lamb wave mode conversion and the processing demands, leading to less effective outcomes. This paper proposes a sign coherence factor and time reversal fusion (SCF-TR) imaging method based on amplitude and phase estimation. This method removes the coherence of array signals during signal reversal and refocusing. It reintroduces the sign coherence component to reduce interference from non-target scattered waves and partially overcome the constraints imposed by the Rayleigh criterion. The method allows imaging at a resolution smaller than the wavelength of Lamb and enhances the quality of the resulting images. In addition, a sparse array design utilizing the White Shark Optimisation Algorithm (WSO) is proposed to streamline the SCF-TR calculation process. This design utilizes sparse full matrix data to improve imaging efficiency. The experimental results show that for single blind hole defects, the SCF-TR method improves the array performance metrics and signal-to-noise ratio by 22.46% and 42.50%, respectively, compared to the TR method. For multiple asymmetric blind hole defects, when the defect size exceeds the resolution threshold, SCF-TR accurately reflects the position and morphology of defects smaller than the wavelength. When the defect size is below the resolution threshold, SCF-TR achieves super-resolution imaging. The sparse array designed using the White Shark Optimization algorithm demonstrates good sidelobe characteristics, effectively reducing sidelobe noise without reducing the array aperture. Moreover, the SCF-TR imaging time is reduced by approximately half while maintaining imaging accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

From the perspective of philology, this study is the first to explore the author information,manuscript content,and literary value of the unpublished and unique manuscript He Yao Zong Bu. Firstly, by examining the physician's birth year, residence, social interactions and handwriting style, it can be determined that the manuscript's author is Yang Shoushan, a renowned doctor of the Shicai School of the Wumen Medical School during the Qing Dynasty. He Yao Zong Bu is one of the two traceable manuscripts currently known that have been handed down by Yang. Secondly,the main content of this book is Yang Shoushan's compilation of nearly 400 surgical formulas and their preparation methods drawn from previous medical experts in Suzhou. The book is concise in structure and rich in formulas,providing a substantial amount of reference material for future generations to study the characteristics of surgical diagnosis and treatment in the Wumen Medical School and summarize surgical thought. Thirdly, the manuscript He Yao Zong Bu contributes rich documentary material to the analysis of the academic thought of Yang Shoushan, a physician of the Shicai School of the Wumen Medical School, medicine. It also provides solid documentary evidence for elucidating the style and pattern of Chen Xintian's surgical formulas,a famous surgeon of the Wumen Medical School.

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated. Results: 666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion: CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t -test, or Log-Rank test according to the data. Results: 593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores. Conclusion: After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Purpose: Periprosthetic fracture (PPF) is one of the severe complications in patients with osteosarcoma and carries the risk of limb loss. This study describes the characteristics, treatment strategies, and outcomes of this complication., Methods: Patients were consecutively included who were treated at our institution between 2016 and 2020 with a PPF of distal femur. The treatment strategies included two types: 1) open reduction and internal fixation with plates and screws and 2) replacement with long-stem endoprosthesis and reinforcement with wire rope if necessary., Results: A total of 11 patients (mean age 12.2 years (9-14)) were included, and the mean follow-up period was 36.5 (21-54) months. Most fractures were caused by direct or indirect trauma (n = 8), and others (n = 3) underwent PPF without obvious cause. The first type of treatment was performed on four patients, and the second type was performed on seven patients. The mean Musculoskeletal Tumor Society (MSTS) score was 20 (17-23). All patients recovered from the complication, and limb preservation could be achieved., Conclusion: PPF is a big challenge for musculoskeletal oncologists, particularly in younger patients. Additionally, PPF poses a challenge for orthopedic surgeons, as limb preservation should be an important goal. Hence, internal fixation with plates and endoprosthetic replacement are optional treatment strategies based on fracture type and patient needs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jin, Su, Du, Hou, Lu, Dai, Lei, Chen and Li.)

Background: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA N 6 -methyladenosine (m 6 A) modification plays a critical role in influencing RNA fate. However, the biological significance of m 6 A modification and its potential regulatory mechanisms in the development of OS remain unclear., Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect m 6 A levels. Western blotting, quantitative real-time PCR (RT-qPCR) and immunohistochemistry (IHC) were used to investigate METTL14 expression levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen the target genes of METTL14. RNA pull-down and RNA immunoprecipitation (RIP) assays were conducted to explore the specific binding of target genes and relevant m 6 A "readers". RNA stability and polysome analysis assays were used to detect the half-lives and translation efficiencies of the downstream genes of METTL14. IHC and clinical data were applied to explore the clinical correlations of METTL14 and its downstream target genes with the prognosis of OS., Findings: We observed the abundance of m 6 A modifications in OS and revealed that METTL14 plays an oncogenic role in facilitating OS progression. MeRIP-seq and RNA-seq revealed that MN1 is a downstream gene of METTL14. MN1 contributes to tumor progression and all-trans-retinoic acid (ATRA) chemotherapy resistance in OS. Mechanistically, MN1 is methylated by METTL14, specifically in the coding sequence (CDS) regions, and this modification is recognized by the specific m 6 A reader insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to prevent MN1 mRNA degradation and promote it translation efficiency. IHC showed that MN1 expression was positively correlated with METTL14 and IGF2BP2 expression in OS tissues. The METTL14-IGF2BP2-MN1 panel demonstrated more promising prognostic value for OS patients than any of these molecules individually., Interpretation: Our study revealed that METTL14 contributes to OS progression and ATRA resistance as an m 6 A RNA methylase by regulating the stability and translation efficiency of MN1 and thus provides both an underlying biomarker panel for prognosis prediction in OS patients., Funding: This work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864)., Competing Interests: Declaration of interests No potential conflicts of interest were disclosed., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism., Methods: CCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects., Results: Notably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway., Conclusions: In brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma., (© 2021. The Author(s).)

Objective: To study the effect of outer membrane vesicles (OMVs) derived from Salmonella typhimurium (ST) on the ultrastructural features and immune function of dendritic cells (DC)., Methods: Mice bone marrow cells were collected aseptically, and myeloid DC were generated by the combined induction and amplification with recombinant mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant mouse interleukin-4 (rm IL-4). Cell morphology was observed under inverted phase contrast microscope and the phenotype was identified with flow cytometry. ST-OMVs were isolated through ultracentrifugation. The survival rate of DC was assessed with CCK-8 assay, and the stimulus concentration of OMVs was henceforth determined. The ultrastructural characteristics of DC loaded with OMVs were observed with transmission electron microscopy. The cytokine secretion, surface molecule expression and phagocytic capacity of DC were examined with flow cytometry., Results: The DC induced and amplified in vitro displayed typical DC phenotype in morphological analysis and the purity of DC exceeded 85%. Transmission electron microscopy showed that there were large numbers of protrusions on the cell surface. After stimulation with ST-OMVs, it was observed that the dendritic structures on the surface of DC were reduced and a large number of phagolysosomes were found in the cytoplasm. In addition, increased numbers of mitochondria, swelling and typical apoptosis were observed. After treatment with ST-OMVs at 5 μg/mL and 10 μg/mL, the secretion of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) of DC increased significantly ( P <0.05). Furthermore, the immature DC could differentiate into mature DCs after stimulation with ST-OMVs, which were characterized by a decrease in phagocytic capacity ( P <0.05) and an upregulation of phenotypic markers ( P <0.05)., Conclusion: ST-OMVs can stimulate DC to produce TNF-α and IL-1β and promote DC maturation and antigen presentation., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Rationale: Drug-induced liver injury (DILI) has a relatively low incidence, whereas the incidence of herb-induced liver injury (HILI) is still under investigation. As a special type of DILI, the diagnosis of drug-induced autoimmune-like hepatitis presents a persistent challenge, because this condition has partial characteristics of both DILI and autoimmune hepatitis (AIH), such as a certain history of medication use and histology that similar is to AIH. Thus, the differential diagnosis between DILI and AIH can be confusing., Patient Concerns: A 67-year-old woman taking xiang-tian-guo for 6 months was admitted to our hospital with a complaint of experiencing jaundice for 2 weeks., Diagnosis: A liver biopsy exhibited interface inflammation, foam cells, and "rosette" -like hepatocytes. She was diagnosed with herb-induced liver injury (hepatocellular and acute), a RUCAM score of 7 (probable), a severity for grade 4 liver injury, and accompanied autoimmune-like changes., Interventions: The patient was instructed to cease the administration of suspicious drugs. The patient also received liver protection and albumin transfusion., Outcomes: After 25 days of hospitalization, the patients aminotransferase levels returned to normal. No recurrence was observed after the administration of the treatments and a close follow-up., Lessons: We must to be vigilant about the safety of xiang-tian-guo as a herbal medicine. When faced with the difficulty of distinguishing between AIH and DILI, long-term follow-up observations for recurrence can aid clinicians in making a judgment., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis., Methods: A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (-174G > C, -572G > C, and -597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment., Results: For IL-6 -174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25-6.19, P = .01, I = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29-5.90, P = .009, I = 3%) models, IL-6 -174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92-3.54, P = .09, I = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95-2.32, P = .08, I = 68%) models, IL-6 -174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 -174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29-4.65, P < .00001, I = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48-4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 -572G>C and -597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed., Conclusion: This meta-analysis indicated that IL-6 -174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 -572G>C and -597G>A polymorphisms and HCC susceptibility.

Objective: To study the effect of Listeria monocytogenes (LM) infection on dendritic cell (DC) immune function, and to compare the difference of immune activation ability on DC cell between bacterial form (WT) and L-form., Methods: C57BL/6 mice were randomly divided into 3 groups and infected intravenously with LM WT, LM L-form or PBS respectively. The ultrastructural characteristics of splenic DC were observed by transmission electron microscopy (TEM). The number of splenic DC, the expression of costimulatory molecules, the secretion of cytokine and the activation of splenic T lymphocyte were detected by flow cytometry., Results: TEM observation found that there were a large number of filamentous pseudopodia on the surface of splenic DC cells. The cytoplasm of DC was homogeneous and its nucleus was large. After phagocytosis of bacteria, the number of pseudopodia on the surface decreased and vacuoles in the cytoplasm increased. The number of splenic DC did not show significant changes at 1 d post infection ( P >0.05). However, the expression of mature phenotypic molecules were significantly up-regulated ( P < 0.05), in L-form infection group, both CD80 and CD86 molecules expressed on DC surface were higher than WT group ( P < 0.05). Compared with control group, the proportion of TNF-α + DC were elevated after LM infection, and the average percentage of TNF-α + DC of L-form infection group was significantly higher than that of WT group ( P < 0.05). At 7 d after infection, the average percentage of CD69 + T cells of L-form group was significantly higher than that of WT group ( P < 0.05)., Conclusion: LM L-form can induce relatively high levels of TNF-α and promote DC maturation so that to enhance their antigen presenting ability., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Rationale: Primary sclerosing cholangitis (PSC) is recognized as an autoimmune-mediated liver disease characterized by progressive biliary inflammation and fibrosis. Some PSC cases with elevated immunoglobulin G4 (IgG4) levels are likely to be misdiagnosed with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC). Thus, distinguishing these 2 diseases is particularly important., Patient Concerns: A 34-year-old male presented with right hypochondrium abdominal intermittent pain and jaundice lasting for 1 month. Here, we present a case of PSC with increased IgG4 levels with improvement of quality of life upon liver transplantation (LT)., Diagnosis: The diagnosis of PSC was confirmed based on clinical symptoms, laboratory test results, imaging findings, pathologic results and a lack of response to steroid therapy., Interventions: LT surgery was performed successfully when his vital parameters were stabilized. Immunosuppressive agents were routinely used after LT., Outcomes: Three years after LT, liver function values show that alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were in the normal range. An abdominal ultrasonography showed no obvious abnormalities., Lessons: There are similar biochemical characteristics and cholangiographic findings between PSC and IgG4-SC. Therefore, distinguishing these 2 diseases is particularly important. LT remains the only option for end-stage PSC. Early diagnosis and effective treatment can achieve a good prognosis.

Rationale: Hereditary hemochromatosis (HH) is a frequent autosomal recessive disease. The pathogenesis of disease is excessive intestinal absorption of dietary iron, resulting in pathologically high iron storage in tissues and organs. As a systemic disease, it has several manifestations including cirrhosis, diabetes mellitus, cardiomyopathy, joint disease. However, a proportion of patients are asymptomatic., Patient Concerns: A 34-year-old man who had abnormal liver function for 9 months without specific symptoms. He underwent various tests, including liver biopsy and genetic testing, which eventually ruled out common liver diseases and identified iron metabolic abnormalities. In addition, we confirmed the pathogenic genes by sequencing the genes of him and his families., Diagnosis: Combined with the symptoms, auxiliary examinations and sequencing results, the patient was diagnosed as HH., Interventions: The patient was given a low iron diet and phlebotomy therapy interval 2 weeks until the ferritin is <100 mg/L., Outcomes: The patient' condition is stable during the follow-up period., Lessons: When clinicians are confronted with unexplained liver dysfunction, the possibility of the HH should be considered. Liver biopsy and gene sequencing are helpful in diagnosis. Phlebotomy treatment is the most economical and practical treatment for HH at present, but it should vary from person to person.

Introduction: Glycogen storage disease (GSD) type IX, characterized by liver enlargement and elevated aminotransferase levels, is the most frequent type of GSD. The global incidence of GSD type IXa is only about 1/100,000 individuals. Case reports of GSD type IX are rare in China. We present the first case report of GSD type IXa in Northeast China caused by mutation of PHKA2., Patient Concerns: An 11-year-old boy was referred to our hospital because of liver enlargement with consistently elevated transaminase levels over 6 months., Diagnosis: Histopathological results following an ultrasound-guided liver biopsy confirmed a diagnosis of GSD. Further genetic testing showed that the patient had GSD type IXa caused by the c.133C>T mutation in PHAK2., Interventions: We placed the patient on a high-protein and high-starch diet and provided hepatoprotective and supportive therapy., Outcomes: The patient's transaminase levels decreased significantly and were nearly normal at 10-month follow-up., Conclusion: This is the first reported case of GSD type IXa in Northeast China. We hope that the detailed and complete report of this case will provide a reference for the diagnosis of liver enlargement of unknown etiology in future clinical practice.

Background: Benzbromarone is a uricosuric agent that reduces proximal tubular reabsorption of uric acid. Because of hepatotoxicity, it has been withdrawn from the market in Europe. Recently, some benefit-risk assessments of benzbromarone suggest that benzbromarone has greater benefits than risks, and the application of benzbromarone in the treatment of gout and hyperuricemia is still under debate., Case Summary: A 39-year-old man was admitted to the hospital for icterus and nausea, and he was treated with benzbromarone (100 mg/d) for 4 mo because of hyperuricemia. He had a 10-year history of beer drinking (alcohol: about 28 g/d). Laboratory data showed severe liver injury and serious coagulation dysfunction; tests for autoimmune antibodies, viral hepatitis, and human immunodeficiency virus were negative. Despite administration of liver function-protecting drugs and efficient supportive treatment, the patient deteriorated quickly after hospitalization and developed grade II encephalopathy within a few days. The patient accepted continuous plasma exchange six times; however, his condition did not improve. Based on suggestions from multidisciplinary consultation, the patient underwent liver transplantation 26 d after admission. Liver specimen pathology results showed massive necrosis consistent with drug-induced liver injury, supporting the diagnosis of acute liver failure associated with benzbromarone. The patient recovered quickly thereafter., Conclusion: This case highlights that clinicians should be on the alert for the severe hepatotoxicity of benzbromarone. Before prescribing benzbromarone, physicians should evaluate the high-risk factors that may lead to liver injury and provide suggestions for monitoring benzbromarone's hepatotoxicity during treatment., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest, and no additional data are available.

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion: Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Li Shicai, a famous physician of Ming Dynasty had a large number of students. Shen Langzhong, who was a student of Li Shicai, was the teacher of Ma Yuanyi, and one of Ma's student was You Zaijing. This inheritance pedigree was called "Li Shicai School" in academic communities. There were little of study on its later physicians after You Zaijing. This paper collated the medical works, genealogy, local chronicles and medical records of Li Shicai and doctors of different generations. We clarified the academic inheritance genealogy of the past four hundred years. Up to now, there have been twelve generations totally.

Rationale: Madelung disease (MD), a rarely reported disease, also known as benign symmetric lipomatosis, a disorder resulting from alcoholic abuse. It's largely under-recognized and under-reported, possibly because of unawareness of the condition by physicians., Patient Concerns: A 45-year-old Chinese man presented with intermittent fatigue and abdominal distension and progressive bilateral breast enlargement. He has been a heavy drinker for ten years before onset of the disease with an average daily alcohol intake of more than 120 g/day., Diagnosis: Due to the patient's symptoms, laboratory test results, radiographic findings, he was diagnosed with MD., Interventions: We treated him with abstinence from alcohol and supportive therapy., Outcomes: The patient is now in stable condition, with improvement in symptoms during follow-up., Lessons: Doctors, confronted with progressive bilateral breast enlargement in a patient with alcoholic liver disease, should be aware of the underreported MD. Recognition of this syndrome could help doctors establish diagnosis and emphasize the importance of alcohol abstinence as the mainstay of management.

Rationale: Renal tubular acidosis (RTA) represents a class of metabolic disorders characterized by metabolic acidosis with a normal plasma anion gap. As a rare complication of primary biliary cirrhosis (PBC), RTA is easily overlooked, likely leading to misdiagnosis., Patient Concerns: A 32-year-old woman who had been diagnosed with PBC at our hospital was found to have hypokalemia due to repeated fatigue for 2 years, and the etiology was unknown., Diagnoses: Due to the laboratory test results, radiographic findings, and pathologic results, she was diagnosed with PBC associated with RTA., Interventions: She was then treated with ursodeoxycholic acid, potassium citrate, and calcium supplements together with activated vitamin D., Outcomes: Thus far, the patient showed a good response to ursodeoxycholic acid, and the clinical symptoms and liver function were significantly improved., Lessons: Physicians that encounter refractory hypokalemia in a patient with PBC should be aware of the presence of RTA. The early diagnosis and treatment of such patients are of paramount importance to alleviate clinical symptoms and delay disease progression.

Rationale: Zieve syndrome, a rarely reported disease resulting from alcohol abuse, consists of a triad of symptoms: hemolytic anemia, cholestatic jaundice, and transient hyperlipidemia. It is largely under-recognized and under-reported, possibly because of unawareness of the condition by physicians. Here, we report a case of Zieve syndrome managed at the Jilin University First Bethune Hospital., Patient Concerns: A 30-year-old Chinese woman presented with a 4-month history of fatigue, yellowish discoloration of the eyes, and tea-colored urine. She had been a heavy drinker for 2 years prior to onset of the disease with an average daily alcohol intake of 60 g/d and more than 80 g/d for the previous 6 months., Diagnosis: The diagnosis of Zieve syndrome was confirmed based on hemolysis and cholestatic jaundice secondary to alcoholic liver disease and heavy drinking. Bone marrow biopsy and liver biopsy both supported the diagnosis., Interventions: We treated her with abstinence from alcohol and supportive therapy., Outcomes: The patient was discharged 14 days after admission with an improvement in symptoms, which continued to subside during the 2-month follow-up period., Lessons: Doctors confronted with hemolysis in a patient with alcoholic liver disease should be aware of the under-reported Zieve syndrome. Recognition of this syndrome could help doctors avoid unnecessary invasive procedures and emphasize the importance of alcohol abstinence as the mainstay of management. Glucocorticoids may not be useful in treating hemolytic anemia in Zieve syndrome., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

A delignification method was employed to extract the polysaccharide from the fruiting body of Phellinus baumii. The three parameters, processing temperature, ratio of water to raw material and amount of acetic acid every time were optimized using the Box-Behnken design. As a result, the optimal extraction conditions were: processing temperature 70.3°C, ratio of water to raw material of 34.7mL/g and amount of acetic acid of 0.32mL every time. Under these conditions, the highest yield of polysaccharide (10.28%) was obtained. The main fraction (PPB-2) purified from PPB was composed of fucose, arabinose, galactose, glucose, xylose and mannose, while glucose was the predominant monosaccharide. PPB-2 exhibited noticeable antioxidant activity and strong protection against oxidative DNA damage. These findings implied that acid-chlorite delignification was a superior method to extract the polysaccharide from P. baumii and PPB-2 may be useful for cancer chemoprevention., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance. The aim of this study was to identify associations between estrogen receptor (ESR) gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population., Methods: Thirty-six patients with PBC (case group) and 35 healthy individuals (control group) from the First Hospital of Jilin University were studied. Whole genomic DNA was extracted from all the participants. Three single-nucleotide polymorphisms (rs2234693, rs2228480, and rs3798577) from ESR1 and two (rs1256030 and rs1048315) from ESR2 were analyzed by a pyrosequencing method. Demographic data and liver biochemical data were collected., Results: Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele (odds ratio [OR] = 2.1277, 95% confidence interval [CI] = 1.1872-4.5517). Haplotypes TGC of ESR1 rs2234693, rs2228480, and rs3798577 were risk factors for having PBC. The C allele at ESR1 rs2234693 was associated with abnormal alkaline phosphatase (OR = 5.2469, 95% CI = 1.3704-20.0895) and gamma-glutamyl transferase (OR = 3.4286, 95% CI = 1.0083-13.6578) levels in PBC patients., Conclusions: ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC. Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC.

Three polysaccharides (PPB-MB, PPB-MW and PPB-MM) were obtained from the fruiting body of Phellinus baumii growth on different culture substrates (mulberry branches, mixed wood sawdust and an equal combination of the two materials) and their chemical composition was investigated. PPB-MM contained the highest contents of neutral sugar (66.59%) and uronic acid (23.38%), followed by PPB-MW and PPB-MB, with PPB-MW having the highest protein content. The three polysaccharides were all composed of six kinds of monosaccharides, namely fucose, mannose, glactose, xylose, arabinose and glucose. The antioxidant activities of the three polysaccharides were determined using lipid peroxidant inhibition, ABTS radical scavenging, and Fe(2+)-chelating assay. Results showed that PPB-MM exhibited the highest antioxidant properties in all the assays. As a result, an equal combination of mulberry branches and mixed wood sawdust serves as a good culture substrate for producing such antioxidant polysaccharides., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Transforming growth factor (TGF)-β, type I receptor (TβRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1-4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients., (© 2013 British Society for Immunology.)

Aim: To explore the effects of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils or polymorphonuclear cells (PMNs) in tuberculosis patients., Methods: The fresh peripheral blood samples from TB patients and healthy adults were incubated with M.tb labeled with FITC, and the percentages of phagocytosis of M.tb by PMNs was measured by flow cytometry (FCM). The fresh peripheral blood samples were incubated with DCFH-DA, and with or without M.tb for different times, the percentage of activation and the ROS production of PMNs were measured by FCM. Whole blood samples were pretreated with IL-12, the changes of phagocytosis, activation and ROS production of PMNs were measured by FCM., Results: The percentages of phagocytosis by PMNs, activation and ROS production of PMNs in both TB patients and healthy adults increased dependent on the time of incubation with M.tb. Only the phagocytosis of M.tb by PMNs at 5 min in TB patients of tuberculosis patients (51.82±6.93)% was obviously higher than that in healthy adults (47.20±4.26)%, (P<0.05). Pretreatment of whole blood with IL-12 before incubation with M.tb, the percentages of phagocytosis, activation and ROS production of PMNs in both TB patients and healthy adults increased in dose dependent manner, but no significant difference was found between both groups., Conclusion: The results indicated that the phagocytosis of M.tb and ROS production by PMNs in TB patients were almost the same as that in healthy controls, except for phagocytosis is higher at early stage. Furthermore, IL-12 can enhance the responsiveness to the phagocytosis and ROS production of PMNs.

No specific treatment can reverse the liver injury in cirrhosis. This study aims to characterize immune status and correlations between cirrhosis induced by HBV and HCV. Phenotypes of peripheral blood lymphocyte subsets (T, NK, regulatory T cells) and Th cytokine secretion were analyzed using flow cytometry in 42 HBV-cirrhotic and 40 HCV-cirrhotic patients. Cirrhotic patients had a lower proportion of CD3(+)CD8(+)T cells and NK cells, while the proportion of CD3(+)CD4(+)T cells and Treg cells were higher than those of healthy controls. The levels of Th2 cytokine (IL-6) in cirrhotic patients were increased, while only the Th1 cytokine (IFN-gamma) increased in HBV-cirrhotic patients. These findings show that there is no difference between the cirrhotic groups except in the IFN-gamma level. In cirrhosis, defects in innate, adaptive immune cells are likely regardless of which virus is involved. A cytokine imbalance may play a role in the development of posthepatitic cirrhosis.

Although it has been known that gammadelta T cells may play an important role in the immune response to infection of Mycobacterium tuberculosis (M. tb), the mechanisms by which the gammadelta T cells participate in the innate and/or acquired immunity to tuberculosis (TB) have not been full elucidated. In the present study, 27 patients with active pulmonary TB and 16 healthy donors (HD) were performed. We found that proportion of IL-17-producing cells among lymphocyte was similar between TB patients and HD, whereas the proportions of gammadelta T cells in IL-17-producing cells (59.2%) and IL-17-producing cells in gammadelta T cells (19.4%) in peripheral blood were markedly increased in TB patients when compared to those in HD (43.9% and 7.7%, respectively). In addition, the proportions of IFN-gamma-producing gammadelta T cells in TB patients were obviously lower than that in HD. Upon re-stimulated with M. tb heat-treated antigen (M. tb-HAg) in vitro, fewer IL-17-producing gammadelta T cells were generated from HD and TB patients, whereas IFN-gamma-producing gammadelta T cells were increased in TB patients compared to that in HD. Our findings in TB patients and healthy human were consistent with other murine investigation that the IL-17-producing gammadelta T cells were main source of IL-17 in mouse model of BCG infection, suggesting that gammadelta T cells might be involved in the formation of tubercular granuloma in pulmonary TB patients, but need further identification.

Objective: To determine the advantage of U1 small nuclear RNA as a ribozyme vector (U1-Rz) to inhibit HCV replication in vivo., Methods: The 3rd stem-loop was substituted by HCV core specific ribozyme to construct an U1-Rz eucaryotic expression plasmid. Then it was co-transfected with pCMV/T7-NCRC Delta-luc into Huh7 cell line mediated by lipofectin. The cell lysis supernatant was subjected to Western blot and lumenometer to determine the luciferase levels., Results: A U1 snRNA chimeric ribozyme was constructed successfully. Both Rz and U1-Rz inhibited luciferase expression in Huh7 by 48.64% and 87.46%, respectively., Conclusion: Rz has more efficacy in cells when using U1 snRNA delivery system. U1 can be an efficient vector for HCV specific ribozyme.

Hypersensitive reaction and pathogenicity (hrp) genes are required for Pseudomonas syringae pv. tomato (Pst) DC3000 to cause disease in susceptible tomato and Arabidopsis thaliana plants and to elicit the hypersensitive response in resistant plants. The hrp genes encode a type III protein secretion system known as the Hrp system, which in Pst DC3000 secretes HrpA, HrpZ, HrpW, and AvrPto and assembles a surface appendage, named the Hrp pilus, in hrp-gene-inducing minimal medium. HrpA has been suggested to be the Hrp pilus structural protein on the basis of copurification and mutational analyses. In this study, we show that an antibody against HrpA efficiently labeled Hrp pili, whereas antibodies against HrpW and HrpZ did not. Immunogold labeling of bacteria-infected Arabidopsis thaliana leaf tissue with an Hrp pilus antibody revealed a characteristic lineup of gold particles around bacteria and/or at the bacterium-plant contact site. These results confirm that HrpA is the major structural protein of the Hrp pilus and provide evidence that Hrp pili are assembled in vitro and in planta.

Bacterial surface appendages called pili often are associated with DNA and/or protein transfer between cells. The exact function of pili in the transfer process is not understood and is a matter of considerable debate. The Hrp pilus is assembled by the Hrp type III protein secretion system of Pseudomonas syringae pv. tomato (Pst) strain DC3000. In this study, we show that the hrpA gene, which encodes the major subunit of the Hrp pilus, is required for secretion of putative virulence proteins, such as HrpW and AvrPto. In addition, the hrpA gene is required for full expression of genes that encode regulatory, secretion, and effector proteins of the type III secretion system. hrpA-mediated gene regulation apparently is through effect on the mRNA level of two previously characterized regulatory genes, hrpR and hrpS. Ectopic expression of the hrpRS gene operon restored gene expression, but not protein secretion, in the hrpA mutant. Three single amino acid mutations at the HrpA carboxyl terminus were identified that affect the secretion or regulatory function of the HrpA protein. These results define an essential role of the Hrp pilus structural gene in protein secretion and coordinate regulation of the type III secretion system in Pst DC3000.

HarpinPss can induce hypersensitive reaction (HR) in tobacco leaves. As superoxide dismutase can inhibit but catalase can not inhibit the development of HR induced by harpinPss, superoxide anion is required for this response. HarpinPss can also induce the release of active oxygen and extracellular alkalinization, two early defence responses in tobacco suspension culture. Diphenylene iodoium, can completely inhibit the induction of HR in tobacco leaves, and the release of active oxygen in the suspension culture system, superoxide anion in these system may be produced by the activation of NADPH oxidase. Ethyleneglycol-bis (beta-aminoethyl) N, N, N'N'-tetraacetic acid (EGTA) can inhibit the development of harpinPss-induced HR and these two early defence responses in suspension culture system. Adding Ca2+ into the medium again, these responses can return to normal level in a short time. Lanthanum chloride, verapamil, neomycin, U-73122, and LiCl can also inhibit these harpinPss-induced responses. Therefore, the influx of Ca2+ mediated by calcium channel and the release of Ca2+ from internal Ca2+ pool may be involved in the two early defense responses induced by harpinPss. Cycloheximide and actinomycin D have no effect on the release of active oxygen but can inhibit harpinPss-induced HR even added them in the intermediate process for inducing HR. It indicates superoxide is just a trigger for HR, and HR is a more complex process that needs the sustained expression of some genes.

No matter when anion channel inhibitors, DIDS (4, 4'-diisothiocyanatostilbene-2, 2'-disulfonic acid) and A9C (anthracene-9-carboxylic acid) added (before, at the same time of or after harpinPss treatment), they can inhibit harpinPss-induced hypersensitive response in tobacco seedlings and release of active oxygen and extracellular alkalinization in tobacco suspension cells. DIDS and A9C also inhibit harpinPss-induced Ca2+ influx. In all these cases, DIDS is more efficient than A9C. It is postulated that anion channel positively regulates calcium channel in plasma membrane, and harpinPss may function through signal transduction mediated by anion channel and calcium channel to regulate cellular Ca2+ concentration and defense responses.

A case of hyaline membrane disease was treated successfully with pulmonary surfactant (PS) isolated from human amniotic fluid. Dosage was 150 mg phospholipid/kg. The exogenous surfactant was instilled into the airway via a tracheal cannula. Clinical symptoms, PO2 and FiO2 improved evidently 24 hours after administration. L/S ratio and phosphatidylglycerol recovered gradually in aspirates. Lung X-ray film manifested "white lung" before instillation of surfactant and showed a striking improvement 3 days after treatment. The duration of mechanical ventilation was 6 days. During the period of recovery complications of patent ductus arteriosus and bacterial pneumonia developed. However, the patient recovered completely and was discharged 32 days after admission.