Deficient chaperone-mediated autophagy in macrophage aggravates inflammation of nonalcoholic steatohepatitis by targeting Nup85.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.

[A protein complex recognition method based on spatial-temporal graph convolution neural network].

OBJECTIVE: To propose a new method for mining complexes in dynamic protein network using spatiotemporal convolution neural network. METHODS: The edge strength, node strength and edge existence probability are defined for modeling of the dynamic protein network. Based on the time series information and structure information on the graph, two convolution operators were designed using Hilbert-Huang transform, attention mechanism and residual connection technology to represent and learn the characteristics of the proteins in the network, and the dynamic protein network characteristic map was constructed. Finally, spectral clustering was used to identify the protein complexes. RESULTS: The simulation results on several public biological datasets showed that the F value of the proposed algorithm exceeded 90% on DIP dataset and MIPS dataset. Compared with 4 other recognition algorithms (DPCMNE, GE-CFI, VGAE and NOCD), the proposed algorithm improved the recognition efficiency by 34.5%, 28.7%, 25.4% and 17.6%, respectively. CONCLUSION: The application of deep learning technology can improve the efficiency in analysis of dynamic protein networks.

A systematic review and meta-analysis on the efficacy of probiotics for bacterial vaginosis.

OBJECTIVE: The current study aimed at assessing the overall efficacy of probiotics for the treatment of bacterial vaginosis (BV) through the review of relevant studies. MATERIALS AND METHODS: A systematic literature review was conducted based largely on the following electronic databases updated to May 2021: Embase, the Cochrane Library, and PubMed, with the use of keywords. The investigators also thoroughly reviewed key pertinent sources in the literature for further inclusion. RESULTS: Eighteen studies including 1651 patients were selected in the present meta-analysis. In comparison with antibiotics, antibiotics plus probiotics significantly decreased the recurrence rate of BV (at 1-3 months and overall analysis) and increased the cure/remission rate of BV (at 1-3 months and overall analysis). Compared with placebo, probiotics decreased the recurrence rate of BV (at 1-3 months and overall analysis) and increased the cure/remission rate of BV (at 1-3 months). Compared with antibiotics, probiotics significantly decreased the recurrence rate of BV (at <1 month, 1-3 months and overall analysis) as well as the incidence of adverse events (AEs) (at less than 1 month) and increased the cure/remission rate of BV (at 1-3 months). CONCLUSIONS: In comparison with short-term probiotics treatment (<1 month), long-term probiotics treatment (1-3 months) yields superior beneficial outcomes and efficacy in the treatment of BV.

Digital learning in medical education: comparing experiences of Malaysian and Japanese students.

BACKGROUND: Medical education has undergone a transformation from conventional to digital learning, enabling learning without any time and place restrictions. Nevertheless, the actual trends of usage and its impact on learning motivation among medical students between developed and developing nations are yet to be investigated. Hence, this study compares the effect of digital learning on learning motivation among Malaysian and Japanese medical students in Universiti Kebangsaan Malaysia (UKM) and Shiga University of Medical Science (SUMS) respectively. METHODS: A modified Students Motivation towards Science Learning (SMTSL) was used to assess the digital learning usage and learning motivation among 150 UKM and 147 SUMS medical students throughout Year 1 to 5. RESULTS: The frequency of digital learning usage and learning motivation among UKM medical students was significantly higher as compared to SUMS (p < 0.001). Electronic books (e-books) were the most preferred source of digital learning among UKM medical students as compared to SUMS medical students who used research articles, e-books, online courses and videos at similar frequencies. UKM medical students in the clinical phase exhibited a significantly higher learning motivation as compared to preclinical students (p < 0.05) but not among SUMS medical students. CONCLUSION: A suitable learning environment should be developed to encourage digital learning usage among different levels of medical students to enhance its complementary role in medical education and augment the level of motivation among medical students in continuous lifelong learning.

LC/MS-Based Global Metabolomic Identification of Serum Biomarkers Differentiating Hepatocellular Carcinoma from Chronic Hepatitis B and Liver Cirrhosis.

Chronic hepatitis B virus (CHB) infection is one of the primary risk factors associated with the development of hepatocellular carcinoma (HCC). Despite having been extensively studied, diagnosing early-stage HCC remains challenging, and diagnosed patients have a poor (3-5%) survival rate. Identifying new approaches to detect changes in the serum metabolic profiles of patients with CHB and liver cirrhosis (LC) may provide a valuable approach to better detect HCC at an early stage when it is still amenable to treatment, thereby improving patient prognosis and survival. In the present study, we, therefore, employed a liquid chromatography-mass spectrometry (LC-MS)-based approach to evaluate the serum metabolic profiles of 30 CHB patients, 29 LC patients, and 30 HCC patients. We then employed appropriate statistical methods to identify those metabolites that were best able to distinguish HCC cases from LC and CHB controls. A mass-based database was then used to putatively identify these metabolites. We then confirmed the identities of a subset of these metabolites through comparisons with the MS/MS fragmentation patterns and retention times of reference standards. The serum samples were then reanalyzed to quantify the levels of these selected metabolites and of other metabolites that have previously been identified as potential HCC biomarkers. Through this approach, we observed clear differences in the metabolite profiles of the CHB, LC, and HCC patient groups in both positive- and negative-ion modes. We found that the levels of taurodeoxy cholic acid (TCA) and 1,2-diacyl-3-ß-d-galactosyl-sn-glycerol rose with the progression from CHB to LC to HCC, whereas levels of 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid were gradually reduced with liver disease progression in these groups. The ROC analysis showed that taurodeoxy cholic acid (TCA), 1,2-diacyl-3-ß-d-galactosyl-sn-glycerol, 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid had a diagnosis performance with liver disease progression. These four metabolites have a significant correlation with alpha fetal protein (AFP) level and age. Our results highlight novel metabolic biomarkers that have the potential to be used for differentiating between CHB, LC, and HCC patients, thereby facilitating the identification and treatment of patients with early-stage HCC.

Mucoadhesive Low Molecular Chitosan Complexes to Protect rHuKGF from Proteolysis: In-vitro Characterization and FHs 74 Int Cell Proliferation Studies.

BACKGROUND: Recombinant Keratinocyte Growth Factor (rHuKGF) is a therapeutic protein used widely in oral mucositis after chemotherapy in various cancers, stimulating lung morphogenesis and gastrointestinal tract cell proliferation. In this research study, chitosan-rHuKGF polymeric complex was implemented to improve the stability of rHuKGF and used as rejuvenation therapy for the treatment of oral mucositis in cancer patients. OBJECTIVE: Complexation of rHuKGF with mucoadhesive low molecular weight chitosan to protect rHuKGF from proteolysis and investigate the effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells. METHODS: The interaction between chitosan and rHuKGF was studied by molecular docking. Malvern ZetaSizer Nano Zs and Fourier-Transform Infrared spectroscopy (FTIR) tests were carried out to characterize the chitosan-rHuKGF complex. In addition, SDS-PAGE was performed to investigate the interaction between chitosan-rHuKGF complex and pepsin. The effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells was studied by MTT assay. RESULTS: Chitosan-rHuKGF complex was formed through the hydrogen bonding proven by the docking studies. A stable chitosan-rHuKGF complex was formed at pH 4.5 and was protected from proteolysis and assessed by SDS PAGE. According to the MTT assay results, chitosan-rHuKGF complex increased the cell proliferation rate of FHs 74 Int cells. CONCLUSION: The developed complex improved the stability and the biological function of rHuKGF.

The regulation of skin pigmentation in response to environmental light by pineal Type II opsins and skin melanophore melatonin receptors.

Coupling skin colour with the light/dark cycle helps regulate body temperature in ectotherms. In X. laevis, nocturnal release of melatonin from the pineal complex induces pigment aggregation and skin lightening. This nocturnal blanching is initiated by a sensor (type II opsin) that triggers melatonin release when light intensity falls below a minimum threshold, and an effector (melatonin receptor) in the skin which induces pigment aggregation. The sensor/s and effector/s belong to two families of G-protein coupled receptors that originated from a common ancestor, but diverged with subsequent evolution. The aim of this work was to identify candidate sensor/s and effector/s that regulate melatonin-mediated skin colour variation. In X. laevis, we identified a developmental time (stage 43/44) when skin lightening depends on pineal complex photosensitivity alone. At this stage, the pineal complex comprises the frontal organ and pineal gland. A total of 37 type II opsin (14 duplicated) and 6 melatonin receptor (3 duplicated) genes were identified through a full genome analysis of the allotetraploid, X. laevis. These genes were grouped into subfamilies based on their predicted amino acid sequences and the presence of specific amino acids essential for their function. The pineal complex expresses mainly blue light sensitive opsins [pinopsin, parietopsin, opn3, and melanopsins (opn4 and opn4b)] and UV-light sensitive opsins (opn5 and parapinopsin), while visual opsins and va-ancient opsin are absent, as determined by RT-PCR and in situ hybridization. The photoisomerase retinal G-protein coupled receptor, and an uncharacterized opn6b opsin, are also expressed. The spectral sensitivity that triggers melatonin secretion, and therefore melanophore aggregation, falls in the visible spectrum (470-650 Î·m) and peaks in the blue/green range, pointing to the involvement of opsins with sensitivities therein. The effector-melatonin receptors expressed in skin melanophores are mtnr1a and mtnr1c. Our data point to candidate proteins required in the neuroendocrine circuit that underlies the circadian regulation of skin pigmentation, and suggest that multiple initiators and effectors likely participate.

[Role and implementation experience of splints in pediatric burn rehabilitation].

The maintenance of posture and anti-contracture treatment are the critical elements of comprehensive burn rehabilitation in the overall treatment period of pediatric burns. Although domestic experts in burn discipline have formulated guidelines for burn rehabilitation, the maintenance of posture and design and manufacture of splints for anti-scar contractures in children with burns are different from that for adults with burns in many ways. Starting with paying the attention to the rehabilitation problems in pediatric burns, especially considering the anatomical, psychological, and social behavior characteristics of children in developmental period, the author's team effectively applies splints to maximize the prevention of contractures in children and maintain and improve the range of their joint movements. The splints designed to prevent contractures in pediatric burns shall fit the small limb and meet their expected goals of rehabilitation. In each aspect of the production and use of splints, it is necessary to fully evaluate and consider the scar characteristics, growth and development status, activity level, and compliance of children, and adaptability and fixation methods of the splints, so as to select the appropriate splint type and formulate the wearing plan.

Real-Life State of Anti-Hepatitis B Virus Drug Choice in Child-Bearing Age Male Patients and Effect on Fertility and Fetal Safety.

Research on effects of anti-hepatitis B virus (HBV) nucleoside analogs on male fertility and birth defects is limited and safety of nucleoside analogs in pregnancy is still a concern. Chronic hepatitis B (CHB) patients in Guangdong province were surveyed using a structured questionnaire. We collected data including medication type, fertility, and birth defects. Moreover, a survey of the knowledge of antiviral nucleoside analogs safety in fertility of male patients was conducted among physicians nationwide. Semen samples of 30 patients were collected. We screened 1050 HBV-positive male patients. Reasons for not receiving antivirals in 150 patients were "did not meet criteria for antiviral therapy," fertility, and financial. Furthermore, 900 participants received antivirals (85.71%, 900/1050), including 792 patients with children and 15.15% (120/792) took anti-HBV treatment when preparing for pregnancy. Based on whether they received antiviral therapy during conception or not, we divided patients into two groups. In the child-bearing age group, 88.33% (106/120) of patients received telbivudine (LDT), whereas the other group mainly received entecavir (ETV) (87.20%, 586/672). No significant difference occurred in birth defect incidence rates between both groups. Furthermore, 558 physicians completed questionnaires. Reasons that influenced drug selection were "patient's condition," "fertility demand," "financial condition," and "compliance." Telbivudine was the first-choice drug (32.80%, 183/558) while tenofovir (TDF) was the second (2.69%, 15/558). Additionally, 61.47% of physicians considered telbivudine or tenofovir as the first choice for male patients who met antiviral criteria, whereas 19% suggested delayed therapy and follow-up until childbirth. No significant changes occurred in semen volume, concentration, mobility, and percentage before and after administration of anti-HBV nucleoside analogs, which did not affect male fertility and birth defect incidence while the desire for pregnancy influenced drug selection and timing of administration. Further research on the effects of analogs on male fertility and fetal safety is required.

De Novo Hepatitis B Virus Infection After Liver Transplantation in Hepatitis B Core-positive Recipients Using Hepatitis B Core-negative Grafts.

BACKGROUND: Hepatitis B core antibody-positive (HBcAb+) graft is known as a risk for de novo hepatitis B virus (HBV) infection in recipients after liver transplantation (LT). However, little is known about the possibility or incidence of de novo HBV infections after LT in hepatitis B surface antigen-negative (HBsAg-)/HBcAb+ recipients using HBsAg-/HBcAb- grafts. The study aimed to evaluate the prevalence of de novo HBV infection in HBsAg-/HBcAb+ recipients using HBsAg-/HBcAb- grafts. A retrospective review was performed with the records of 1129 adult patients who underwent primary LT at a single institution in an HBV endemic area between January 2000 and December 2013. A total of 78 patients (6.9%) were reviewed for de novo HBV infection after LT. De novo HBV infection was developed in 1 patient (1.28%). The patient was a 65-year-old woman who underwent LT due to alcoholic liver cirrhosis. De novo HBV was not related to graft loss or death and well treated with tenofovir. In conclusion, de novo HBV infections may occur in HBsAg-/HBcAb+ recipients using HBsAg-/HBcAb- grafts, and caution is needed in these patients.

Urinary Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Renal Injury in Liver Transplant Recipients Using Calcineurin Inhibitors.

BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early biomarker of renal injury. We examined the feasibility of using uNGAL as an early predictor of renal impairment in patients under calcineurin inhibitors in liver transplant recipients. METHODS: From urine samples obtained from liver transplant recipients, the glomerular filtration rate (GFR) at the time of urine sampling was compared with that at 5 to 7 months later. Patients were divided into 3 groups according to initial GFR and then divided into 2 groups according to the uNGAL level of 25 ng/mL. Progression of renal injury (PRI) was defined as a decrease in the GFR of more than 5 mL/min/1.73 m2 in the mild or moderate groups, or if a normal group patient shifted to the mild or moderate group. RESULTS: Fifty-one patients were enrolled. The mean uNGAL level was higher in the moderate group than in the normal and mild groups (18.38 ± 14.31 vs 7.74 ± 8.13; P < .01). A proportion of uNGAL-high was also higher in the moderate group than in the mild group (40% vs 5%; P = .03). uNGAL-high was a risk factor for 6-month PRI (odds ratio, 60.375; 95% confidence interval, 1.283-4088.25; P = .037) and 1-year PRI (odds ratio, 21.311; % confidence interval, 0.947-479.578; P = .054). CONCLUSIONS: A uNGAL of >25 ng/mg can be a marker for moderate renal impairment (GFR of 30-59 mL/min/1.73 m2) and a predictor of PRI at 6 months in patients using calcineurin inhibitors. Renal protection strategies should be considered in liver transplant recipients with a uNGAL of >25 ng/mg in spot urine sampling.

Challenging Alveolar Hemorrhage Complicating Pneumonia After Liver Transplantation: A Case Report.

Alveolar hemorrhage is a life-threatening clinical syndrome often initially thought to be atypical pneumonia. Association with hematopoietic stem cell transplantation is well studied, but not with solid organ transplantation. We report a case of a 54-year-old woman presented with fever and shortness of breath on the third posttransplant day after deceased donor liver transplantation. Imaging studies showed diffuse bilateral pulmonary infiltrates and a positive sequential bronchoalveolar lavage test was revealed during bronchoscopy. Cytomegalovirus antigenemia was present in 8/200,000 white blood cells; Aspergillus galactomannan and Pneumocystis jirovecii were also present. However, only Aspergillus hyphae were found in the sputum culture. Management strategy aimed to treat underlying infections, provide adequate respiratory support, and control inflammation. We proposed that diffuse alveolar hemorrhage should be considered as differential diagnosis in early pulmonary complications after liver transplantation. Early diagnosis and aggressive treatment protocol is the key for a good outcome.

Initial experience with purely laparoscopic living-donor right hepatectomy.

BACKGROUND: There may be concerns about purely laparoscopic donor right hepatectomy (PLDRH) compared with open donor right hepatectomy, especially when performed by surgeons accustomed to open surgery. This study aimed to describe technical tips and pitfalls in PLDRH. METHODS: Data from donors who underwent PLDRH at Seoul National University Hospital between December 2015 and July 2017 were analysed retrospectively. Endpoints analysed included intraoperative events and postoperative complications. All operations were performed by a single surgeon with considerable experience in open living donor hepatectomy. RESULTS: A total of 26 donors underwent purely laparoscopic right hepatectomy in the study interval. No donor required transfusion during surgery, whereas two underwent reoperation. In two donors, the dissection plane at the right upper deep portion of the midplane was not correct. One donor experienced portal vein injury during caudate lobe transection, and one developed remnant left hepatic duct stenosis. One donor experienced remnant portal vein angulation owing to a different approach angle, and one experienced arterial damage associated with the use of a laparoscopic energy device. One donor had postoperative bleeding due to masking of potential bleeding foci owing to intra-abdominal pressure during laparoscopy. Two donors experienced right liver surface damage caused by a xiphoid trocar. CONCLUSION: Purely laparoscopic donor hepatectomy differs from open donor hepatectomy in terms of angle and caudal view. Therefore, surgeons experienced in open donor hepatectomy must gain adequate experience in laparoscopic liver surgery and make adjustments when performing PLDRH.

Pure laparoscopic living donor hepatectomy: Focus on 55 donors undergoing right hepatectomy.

Although laparoscopic donor hepatectomy is increasingly common, few centers with substantial experience have reported the results of pure laparoscopic donor right hepatectomy (PLDRH). Here, we report the experiences of 60 consecutive liver donors undergoing pure laparoscopic donor hepatectomy (PLDH), with most undergoing right hepatectomy. None of the 60 donors who underwent PLDH had intraoperative complications and none required transfusions, reoperation, or conversion to open hepatectomy. Forty-five donors who underwent PLDRH between November 2015 and December 2016 were compared with 42 who underwent conventional donor right hepatectomy (CDRH) between May 2013 and February 2014. The total operation time was longer (330.7 vs 280.0 minutes; P < .001) and the percentage with multiple bile duct openings was higher (53.3% vs 26.2%; P = .010) in the PLDRH group. However, the length of postoperative hospital stay (8.4 vs 8.2 days; P = .495) and rate of complications (11.9% vs 8.9%; P = .733) and re-hospitalizations (4.8% vs 4.4%; P = 1.000) were similar in both groups. PLDH, including PLDRH, is feasible when performed by a highly experienced surgeon and transplant team. Further evaluation, including long-term results, may support these preliminary findings of comparative outcomes for donors undergoing PLDRH and CDRH.

Effects of microencapsulated Lactobacillus plantarum LIP-1 on the gut microbiota of hyperlipidaemic rats.

The in vivo effects of administering free and microencapsulated Lactobacillus plantarum LIP-1 cells (2·0×109 colony-forming units/d) were evaluated in high-fat-diet-induced hyperlipidaemic rats. Results from real-time quantitative PCR targeting to LIP-1 cells showed a higher colon colonisation count of LIP-1 in the rats receiving microencapsulated cells compared with free cells (P<0·05). Moreover, the microencapsulated LIP-1 treatment resulted in a more obvious lipid-lowering effect (P<0·05). Meanwhile, their faecal samples had significantly less lipopolysaccharide-producing bacteria (especially Bilophila, Sutterella and Oscillibacter) and mucosa-damaging bacteria (Bilophila and Akkermansia muciniphila), whereas significantly more SCFA-producing bacteria (P<0·05) (namely Lactobacillus, Alloprevotella, Coprococcus, Eubacterium and Ruminococcus) and bacteria that potentially possessed bile salt hydrolase activity (Bacteroides, Clostridium, Eubacterium and Lactobacillus), and other beneficial bacteria (Alistipes and Turicibacter). Further, Spearman's correlation analysis showed significant correlations between some of the modulated gut bacteria and the serum lipid levels. These results together confirm that microcapsulation enhanced the colon colonisation of LIP-1 cells, which subsequently exhibited more pronounced effects in improving the gut microbiota composition of hyperlipidaemic rats and lipid reduction.

[Effects of functional training combined with self-made hand flexing training band in treatment of scar contracture after burn injury of dorsal hand].

Objective: To observe the effects of functional training combined with self-made hand flexing training band in treatment of scar contracture after burn injury of dorsal hand. Methods: Forty-six patients with scar contracture after deep partial-thickness or full-thickness burn injury of dorsal hand hospitalized in our department from March 2013 to February 2015 were divided into routine training group (RT, n=18) and comprehensive training group (CT, n=28) according to their willingness. Two weeks after the wounds were healed, patients in group RT were treated with functional training of hands and self-made pressure gloves, while patients in group CT were treated with self-made hand flexing training band (consisting of nylon strap, flexing band, and velcro) on the basis of those in group RT. All patients were treated for 3 months. Before and after treatment, scar condition of affected hands was assessed with Vancouver Scar Scale (VSS). The range of motion of joints of affected hands was measured by Total Active Movement (TAM) Scale. The function of affected hands was evaluated by Carroll Upper Extremity Function Test. Data were processed with t test, chi-square test, and Mann-Whitney U test. Results: (1) The score of VSS in patients of group RT was (10.0±1.9) points before treatment and (4.4±1.4) points after treatment, with the improved score of (5.6±1.0) points. The score of VSS in patients of group CT was (10.5±1.8) points before treatment and (4.6±1.4) points after treatment, with the improved score of (5.9±1.2) points. There was no statistically significant difference in the improved score of patients between the two groups (t=0.834, P>0.05). The score of VSS in patients of groups RT and CT after treatment was significantly lower than that before treatment (with t values respectively 14.014 and 10.003, P values below 0.01). (2) Before treatment, the ratios of excellent and good results according to TAM were 2/9 in patients of group RT and 3/14 in group CT, with no statistical differences between them (χ(2)=2.140, P>0.05). After treatment, the ratio of excellent and good results according to TAM in patients of group CT (6/7) was higher than that in group RT (5/9, χ(2)=0.023, P=0.038). The ratios of excellent and good results according to TAM in patients of groups RT and CT after treatment were significantly higher than those before treatment (with Z values respectively -2.023 and -4.780, P values below 0.05). (3) The improved score of hand function in patients of group CT was (26±12) points, which was higher than (15±7) points in group RT (t=3.278, P=0.002). The score of hand function in patients of groups RT and CT after treatment was significantly higher than that before treatment (with t values respectively 2.628 and 6.125, P values below 0.05). There were no significant differences in grades of hand function of patients between the two groups before treatment (Z=-0.286, P>0.05). After treatment, the grade of hand function in patients of group CT was higher than that in group RT(Z=-1.993, P=0.046). The grades of hand function in patients of groups RT and CT after treatment were significantly higher than those before treatment (with Z values respectively -2.717 and -4.998, P values below 0.01). Conclusions: For patients with scar contracture after burn injury of dorsal hand, early functional training combined with hand flexing training band can improve the range of motion of hand joints and functional recovery of hand, and the result was better than functional training alone.

Efficacy and Safety of Generic Mycophenolate Mofetil (My-rept) 500-Milligram Tablets in Primary Liver Transplant Recipients.

BACKGROUND: Generic immunosuppressants may be cost-effective if clinical outcomes are equivalent to the brand-name medications. Mycophenolate mofetil in the form of My-rept may be cost-effective being a generic immunosuppressant, which is available as a 500-mg tablet as well as a 250-mg capsule (Chong Kun Dang Pharmaceutical Corporation, Seoul, Korea). OBJECTIVE: This study aimed to evaluate the efficacy, safety, cost-effectiveness, and convenience of My-rept 500-mg tablets in liver transplant recipients. SETTING: The setting was an outpatient liver transplantation clinic of a tertiary hospital in Korea. METHOD: A phase 4, single-center, open-label, noncomparative study was undertaken. A total of 50 patients were recruited. Acute transplant rejection, changes in blood chemistry, white blood cell count, assessments of renal function, occurrence of adverse drug reactions, and other characteristics of the patients were recorded for 24 weeks. After study termination, a satisfaction survey was conducted. RESULTS: All enrolled patients and their liver grafts had survived for 24 weeks post-transplantation. No episodes of acute rejection were reported. Nine patients (18.8%) presented with adverse drug reactions that had been commonly reported with the use of other mycophenolate mofetil products, and no serious adverse drug reactions were reported. CONCLUSION: In conclusion, the My-rept 500-mg tablet appears to be feasible and convenient for administration to recipients of a liver transplant.

Primary Living-donor Liver Transplantation Is Not the Optimal Treatment Choice in Patients With Early Hepatocellular Carcinoma With Poor Tumor Biology.

OBJECTIVE: Liver resection (LR) and living-donor liver transplantation (LDLT) are considered the two potentially curative treatments for hepatocellular carcinoma (HCC). The aim of this study was to investigate whether there is a difference in the oncologic outcomes between LR and LDLT according to tumor biology. METHODS: Patients (137 LDLTs and 199 LRs) were stratified into four groups by tumor biology according to the number of risk factors for recurrence (preoperative alpha-fetoprotein >200 ng/mL, Edmonson grade 3 or 4, tumor size >3 cm, and presence of microvascular invasion). RESULTS: In the favorable tumor biology patients (groups I and II), there was a significantly worse recurrence-free survival rate in those patients who underwent LR compared to those who underwent LDLT (group I, P = .002; group II, P = .001). The overall survival rates in the LR and LDLT groups were not different (group I, P = .798; group II, P = .981). In the poor tumor biology patients (groups III and IV), there was no significant difference between the two groups in terms of recurrence-free survival rate (group III, P = .342; group IV, P = .616). The LDLT group showed a significantly lower overall survival rate (group III, P = .001; group IV, P = .025). CONCLUSIONS: Primary LDLT should not be recommended in early stage HCC patients with poor tumor biology because of lower survival rates and a high chance of HCC recurrence.

Usefulness of PIVKA-II After Living-donor Liver Transplantation for Hepatocellular Carcinoma.

OBJECTIVE: Prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) is a useful tumor marker for hepatocellular carcinoma (HCC). However, the usefulness of post-transplantation surveillance with PIVKA-II is not clear. We evaluated the clinical value of PIVKA-II in monitoring HCC recurrence after living-donor liver transplantation (LDLT). METHODS: One hundred twenty patients who had undergone LDLT for HCC from February 1999 to December 2010 and whose serum alpha-fetoprotein (AFP) and PIVKA-II had been measured sequentially before and after LDLT were included in this study. Patients were classified into four groups according to the preoperative level of AFP and PIVKA-II (group I, normal AFP and PIVKA-II; group II, elevated AFP; group III, elevated PIVKA-II; and group IV, elevated both AFP and PIVKA-II). RESULTS: Preoperative PIVKA-II level tended to increase with increasing tumor size, number of nodules, presence of microvascular invasion, and poor differentiation. In 27 patients developing recurrent HCC after LDLT, the sensitivity of AFP and PIVKA-II was 59.2% and 88.8%, respectively. When the two markers were combined, the sensitivity increased to 92.5%. Especially, the sensitivity for PIVKA-II was high at groups I and III (100.0% for both, respectively). In patients in groups I, III, and IV, an elevated PIVKA-II level was the most common first sign of HCC recurrence after LDLT. An elevated PIVKA-II level was the most common first sign of recurrence, regardless of recurrence site. CONCLUSIONS: PIVKA-II might be a useful tumor marker in the monitoring of recurrence after LDLT, complementary to AFP.