[Preliminary study of antimicrobial peptide cathelicidin-PY therapy in mice with acute liver failure].

Objective: To investigate the feasibility of cationic antimicrobial peptide cathelicidin-PY(PY) therapy through a mouse model of acute liver failure. Methods: The ability of different concentrations of antimicrobial peptide PY to neutralize endotoxin / lipopolysaccharide (LPS) in vitro was detected by Limulus Amebocyte Lysate (LAL) assay. Cell counting kit-8 (CCK-8) was used to detect the toxic effect of different concentrations of antimicrobial peptide PY on mouse monocyte macrophages (RAW264.7). An in vitro hemolysis experiment was used to evaluate the activity of antimicrobial peptide PY on healthy human erythrocytes. D-galactosamine combined with LPS- induced mouse model of acute liver failure was constructed. The antimicrobial peptide PY effect on survival rate of mouse model was observed. HE staining was used to observe the pathological changes of liver tissue. Immunohistochemistry and Western blotting were used to detect the expression of apoptosis-associated protein caspase-3. Intra-group comparisons were performed using t-test and analysis of variance. χ (2) test was used for the comparison of rates. Results: An in vitro experiment showed that the endotoxin neutralization rate was higher at very low dose (0.01 µmol/L), and exceeded 70% at medium-dose (10-40 µmol/L), and the difference between groups with different concentration was statistically significant (F = 569.22, P < 0.05). Medium-dose antimicrobial peptide PY had strong endotoxin neutralizing effect, low cytotoxicity and hemolytic activity. Moreover, in vivo experiments showed that the degree of liver injury and survival rate of mouse model was significantly improved with the medium-dose of antimicrobial peptide PY. Immunohistochemistry results showed that the expression of caspase-3 in the liver tissue was significantly depleted in the medium-dose group than that of the liver failure group, and the results were consistent with protein immunoblotting testing. Conclusion: Antimicrobial peptide PY possesses a strong ability to neutralize endotoxin and few toxic side effects. A specific dose of antimicrobial peptide PY can attenuate hepatocyte apoptosis and significantly improve the survival rate of animal model, and thus provides a new idea for the liver failure treatment.

[Establishment of clinical features and prognostic scoring model in early-stage hepatitis B-related acute-on-chronic liver failure].

Objective: To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients. Results: Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs(P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion: HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

[Effects of different drugs on bronchial stenosis by TGF-ß/mTOR signaling pathway in rabbit model].

Objective: To investigate the effect of different drugs on tracheal stenosis caused by transforming growth factor-ß/rapamycin target protein (TGF-ß/mTOR) signaling pathway. Methods: Thirty rabbits were randomly divided into normal control group, normal saline group, penicillin group, budesonide group and erythromycin group. The normal control group was not treated,and tracheal stenosis models were established in the other groups. From the 1st to 10th day after modeling, each group was respectively administered with normal saline (0.75 ml/kg, 2 times/d), intramuscular injection of penicillin (40 000 U/kg, 2 times/d), gastric administration of erythromycin (12.5 mg/kg, 2 times/d), inhalation of budesonide (0.05 mg/kg, 2 times/d). Rabbits were sacrificed on the 11th day after surgery, and tracheal specimens were collected to measure the degree of tracheal stenosis. Relative mRNA expression level of interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß), Type Ⅰ collagen (COL-1), Type Ⅲ collagen (COL-3), and Sirtuin 1 (SIRT-1) were detected by Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR); protein expression of mTOR, phosphorylated protein kinase B (p-AKT), vascular endothelial growth factor (VEGF),SIRT-1 were detected by immunohistochemical analysis; protein expression of nuclear factor κB (NF-κB),phosphorylated nuclear factor κB (p-NF-κB),protein kinase B (AKT),p-AKT,mTOR were detected by Western blotting. Results: The degree of stenosis of normal control group was (14.02±2.86)%, saline group was (64.14±3.21)%, penicillin group was (49.11±2.96)%, budesonide group was (39.52±2.09)%, erythromycin group was (32.60±4.27)%. The differences between any two groups were statistically significant (all P<0.05). Except between erythromycin group and normal control group, the differences in relative expression of IL-6 mRNA between any two groups (1.00±0.00, 9.02±1.50, 4.25±0.87, 2.53±0.17, 1.31±0.56) was statistically significant (all P<0.05), and the differences in relative expression of TGF-ß mRNA among all groups (1.00±0.00, 6.92±0.84, 3.83±0.44, 2.13±0.25, 1.40±0.15) were statistically significant (all P<0.05). The relative expression of SIRT-1 mRNA among all the groups (1.000±0.000, 0.209±0.042, 0.375±0.034, 0.555±0.028, 0.667±0.032) was statistically significant different (all P<0.05); except between erythromycin group and budesonide group,the protein levels of SIRT-1 among all other groups (16.93±2.28, 4.77±1.45, 7.70±0.61, 10.76±1.04, 11.03±1.10) were statistically significant different (all P<0.05). The protein levels of mTOR (9.28±4.56, 58.18±8.12, 44.75±5.56, 32.82±5.99, 24.73±3.56) and p-AKT (16.57±4.86, 61.79±6.66, 42.98±5.99, 32.79±5.34, 24.00±4.40) determined through immunohistochemistry of all groups were statistically significant different (all P<0.05). The protein levels of NF-κB, p-NF-κB, AKT, p-AKT and mTOR determined through Western blotting had the same trend as that of determined through immunohistochemistry. The protein expression of NF-κB,AKT and mTOR in saline group were significantly higher than other groups; those protein expression of erythromycin group was lower than budesonide group and penicillin group. Except between the erythromycin group and the normal control group, the protein expression of mTOR in other groups was statistically significant different (all P<0.05). Conclusion: Penicillin,erythromycin and budesonide can alleviate inflammation by increasing SIRT-1, alleviate tracheal scar hyperplasia induced by TGF-beta/mTOR pathway, and reduce the degree of tracheal stenosis in rabbits.

[Model for end-stage liver disease combined with arterial blood lactate to assess the prognosis of hepatitis B virus-associated acute-on-chronic liver failure: a retrospective analysis of 97 cases].

Objective: To explore the prognostic value of model for end-stage liver disease (MELD) combined with arterial blood lactate (Lac) in admitted patients with hepatitis B virus-associated acute- on-chronic liver failure (HBV-ACLF). Methods: Clinical data of 97 cases with hepatitis B virus-associated acute- on-chronic liver failure (HBV-ACLF) admitted to the First Affiliated Hospital of Suzhou University between March 2016 and March 2018 was retrospectively analyzed. Age, gender, complications, MELD score, lactic acid (Lac), total bilirubin (TBil), creatinine (Cr), serum albumin (Alb), high-sensitivity C-reactive protein (CRP), white blood cell count (WBC), platelet count (PLT), hematocrit (Hct), quantification of HBV DNA and HBsAg, and organ support treatment (artificial liver support system, renal replacement therapy and mechanical ventilation ) were documented after admission. The primary endpoint of treatment was death due to ineffective medical treatment during hospitalization, abandonment of medical treatment due to deterioration of the health condition, and switch to liver transplantation for patients with poor medical treatment. The risk factors for primary endpoint of treatment were analyzed by binary logistic regression. Hosmer-Lemeshow test was used to evaluate the goodness of fit for the scoring system, and the ROC to predict the prognosis of MELD-Lac. Results: Ninety-seven cases with HBV-ACLF were included, 56 cases had good prognosis, and 41 cases had bad prognosis (including two cases with poor medical treatment and liver transplantation). The overall improvement rate was 57.7%. MELD score and Lac value in treated group was significantly lower than non-treated group. Bivariable and multivariable logistic regression analysis showed that the MELD score [odds ratio (OR = 1.806)], and Lac score [odds ratio (OR = 1.820)] was the risk factor for hospitalization and mortality in patients with liver failure (P < 0.05). The area under the ROC curve (AUC) and the 95% confidence interval (95% CI) of prognostic patients with MELD-Lac were significantly better than Lac and MELD scores [0.923 (0.84 to 1.00) vs. 0.804 (0.067 to 0.942) and 0.864 (0.75). 0.977)], P < 0.05. When the MELD-Lac Youden index was set at 0.746, the optimal threshold was 18.36, and the sensitivity and specificity were 91.3% and 83.3%, respectively. Conclusion: MELD-Lac score has a high prognostic value in HBV-ACLF patients.

[An investigation on professional performance of optometric refraction in spectacles stores in Anyang city of Henan Province].

Objective: To investigate the methods of optometric refraction adopted for adolescents in spectacles stores in Anyang city of Henan Province and the professional performance of optometric refraction. Methods: Cross-sectional study. Maps and yellow pages were used to collect the information of 131 spectacles stores in Anyang city. A questionnaire was used to investigate spectacles stores that had optometry equipment and can provide refraction prescription and spectacles in this city. The questionnaire covered (1) the process of optometric refraction, including whether cycloplegic refraction was conducted for adolescents and children if it was their first-time optometry and the type of cycloplegics,and (2) the opticians' knowledge on optometric refraction for adolescents and children, such as necessity of cycloplegic refraction for adolescents and children and age cut-offs. According to whether they used a comprehensive refractometer, the optometry methods were divided into conventional optometry and medical optometry. Results: Of 131 spectacles stores in Anyang city, 127 were enrolled. A total of 127 questionnaires were distributed and returned with an effective rate of 100%. Conventional optometric refraction was performed in 53 stores (41.73%), and medical optometric refraction was performed in 74 stores (58.27%). Cycloplegic refraction was conducted in only 4 spectacles stores (3.15%) for adolescents and children upon their first-time optometry. The fogging method of refraction was adopted in 31 stores (24.41%), while optometric refraction was directly conducted in 92 stores (72.44%) without controlling accommodation. As for the use of cycloplegia at initial optometric refraction of children, cycloplegia was objected to in 4 stores,and thought to be no need in 28 stores including 6 stores in which the fogging method was used to replace cycloplegia. In 68 stores, cycloplegia was performed if wanted, or children could go to a hospital for it. In 12 stores, the use of cycloplegics was determined by children's vision and diopters. In 5 stores, children were suggested to go to a hospital for cycloplegic refraction. Cycloplegic refraction was required in only 4 stores. As to the age cut-offs of cycloplegic refraction, 6 years old, 12 years old, and 18 years old were considered as the boundary in 7 stores, 33 stores, and 9 stores, respectively.In 11 stores, age was only considered for amblyopia and hyperopia, and in 67 stores, it was not realized. Conclusions: Cycloplegic refraction was found to be conducted for adolescents and children in only 3% of the spectacles stores in Anyang city. Moreover, most of the spectacles store opticians did not support to use cycloplegia before optometric refraction for adolescents and children and lacked knowledge on the age cut-offs of cycloplegic refraction.Standardized training of cycloplegic refraction should be further strengthened. (Chin J Ophthalmol, 2019, 55: 576-581).

[Expression and significance of autophagy in rabbit model of tracheal stenosis].

Objective: To investigate the expression and significance of autophagy in rabbit model of tracheal stenosis. Methods: A total of 18 rabbits were equally divided into 3 groups (blank control group, saline group, erythromycin group) in accordance with the random number table. After rabbit model of tracheal stenosis was established, no treatment was done with blank control group. Saline group was atomized with saline (0.54 mg/kg, 2 times/day), and erythromycin group was fed on erythromycin (7.5 mg/kg, 2 times/day) for 7 days before and 10 days after the operation. On the eleventh day, rabbits were executed, and their trachea were collected. The proportion of collagen fiber area of tracheal lamina propria (LP) and epithelium (EP) was assessed by Masson staining. The mRNA of autophagy associated gene-3 (ATG3) and autophagy associated gene-5 (ATG5) of tracheal mucosa were assessed by Real-Time Polymerase Chain Reaction (RT-PCR). The protein of microtubule-associated protein 1 light chain ß(3) (LC3B), ATG3 and ATG5 were assessed by Western blot. Results: The proportion of collagen fiber area of tracheal LP and EP of blank control group was (6.79±0.67)%, saline group was (40.55±5.40)%, erythromycin group was (27.48±0.43)%. The differences between any two groups was all statistically significant (all P<0.01). The relative value of ATG3 mRNA and ATG5 mRNA in saline group were significantly lower than blank control group (all P<0.01). Those value in erythromycin group were significantly higher than the saline group (all P<0.01). The protein levels of LC3B-Ⅱ/Ⅰ, ATG3 and ATG5 in saline group were significantly lower than blank control group (all P<0.01). After low dose of erythromycin intervention, all the protein levels were significantly higher than the saline group (all P<0.01). Conclusions: The expression of autophagy is decreased in rabbit model of trachea stenosis. Low dose of erythromycin could increase the expression of autophagy and at the same time alleviate the degree of fibrosis of the tracheal mucosa. Autophagy may alleviate tracheal fibrosis through up-regulating its expression level and play a protective role.

[Effect of low dose erythromycin on the proliferation of granulation tissue after tracheal injury].

Objective: To investigate the effect of low dose erythromycin on the proliferation of granulation tissue after tracheal injury. Methods: Forty-two rabbits were randomly divided into 7 groups (n=6 each), group A (saline control group), group B (penicillin group), group C (low dose erythromycin group), group D (low dose erythromycin and penicillin group), group E (budesonide group), group F (low dose erythromycin and budesonide group), group G (low dose erythromycin, penicillin and budesonide group). All rabbits received tracheotomy, and the tracheal mucosa was scraped with a nylon brush 20 times for tracheal stenosis model. Rabbits were treated with corresponding drugs from a week before operation to 9 days after operation. The serum concentrations of transforming growth factor - beta 1 (TGF-ß(1)), vascular endothelial growth factor (VEGF), interleukin (IL) -6, IL-8 were determined and the tracheal specimens were harvested for measuring degree of stenosis on the 10th day after operation. Results: Serum concentrations of TGF-ß(1) in group A, B, C, D, E, F and G were (17.6±1.3), (18.2±3.1), (13.0±1.1), (14.0±1.0), (21.0±6.1), (13.6± 3.5), (8.2±1.3) ng/L; VEGF were (88.1±4.1), (85.8±4.3), (58.1±6.3), (56.5±2.4), (87.8±2.8), (57.0±3.7), (34.3±6.7) ng/L; IL-6 were (67.8±4.0), (66.1±3.5), (54.1±4.8), (52.1±3.2), (64.6±4.9), (49.4±4.2), (35.9±3.7) ng/L; IL-8 were (112.8±5.2), (116.6±4.1), (88.0±6.2), (85.5±3.5), (114.4±4.6), (82.6±3.8), (55.9±6.0) ng/L, respectively. The serum concentrations of TGF-ß(1), VEGF, IL-6 and IL-8 in group C, D, F and G were significantly lower than those in group A, B and E (all P<0.05). Compared with the other groups, the serum concentrations in group G were the lowest (all P<0.05). All 42 rabbits had tracheal stenosis with different degrees of proliferation of granulation tissue. The degree of tracheal stenosis in Group A, B, C, D, E, F and G were (53.3±4.4)%, (48.2±5.0)%, (24.3±4.4)%, (29.5±3.2)%, (47.8±6.5)%, (27.9±3.1)%, (15.6±2.0)%, respectively. The degree of tracheal stenosis in group C, D, F and G was significantly lower than that in group A, B and E, which had statistical differences (all P<0.05). Compared with the other groups, the degree of tracheal stenosis in group G was the lowest (all P<0.05). Conclusions: Low dose of erythromycin can effectively inhibit the proliferation of granulation tissue after tracheal injury in rabbits. And it has better effectiveness when combined with other antibiotics and hormone.

[Immune status of liver failure patients and related immune regulation therapy].

Liver failure refers to a series of clinical syndromes manifesting as coagulation disorders, jaundice, hepatic encephalopathy, ascites, and other decompensated abnormalities due to serious hepatic dysfunction or decompensation in terms of synthesis, detoxification, excretion, and biological transformation caused by a variety of factors. In recent years, with the development of the research on immunological pathogenesis of liver failure, the "three-hit" theory clarifies the pathogenesis of liver failure. Major therapeutic strategies for liver failure are to prevent hepatocyte necrosis, promote hepatocyte regeneration, create a good internal environment for hepatocyte regeneration, and actively prevent and treat complications. An understanding of the immune status of liver failure patients and early application of glucocorticoids at right timing may help to improve prognosis and reduce adverse reactions. Establishment of a quantitative or functional balance between different cell subsets and new thoughts on some key cytokines may provide new directions and targets for immune regulation of liver failure.

[The questionnaire survey on glaucoma diagnosis and treatment in China (2016)].

Objective: To investigate the present situation of diagnosis and treatment for primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and awareness of the relevant progress among Chinese ophthalmologists. Methods: This study was a cross-sectional, non-randomized sampling survey. Participants were ophthalmologists who attended the 11st Chinese Glaucoma Society Congress during November 11 to 12, 2016. They were invited to fill out a questionnaire. The questionnaire included participants' basic information and their knowledge about glaucoma diagnosis and treatment. The data collected through questionnaire were analyzed with SAS9.4. Results: A total of 450 questionnaires were distributed and 372 valid questionnaires were retrieved, with a response rate of 82. 7%(372/450). ISGEO classification system was adopted by 58.9% (219/372) of the participants as the diagnostic criteria for PACG. Of the respondents, 48.1% (179/372) of the participants believed that "anterior chamber angle closure mechanism-based PACG classification system" was more instructive for treatment, the percentage was higher than ISGEO classification system (42.2%, 157/372). Most (72.3%, 269/372) of the participants knew the 3-minute dark room prone test, but only 27.7%(103/372) of them applied it in clinical practice. A total of 83.4%(310/372) of the participants believed that low cerebrospinal fluid pressure is a risk factor for POAG. In all, 71.8% (267/372) of the participants reported that their institutes had applied compound trabeculectomy with adjustable suture, with 76.9%(286/372) of the participants agreeing that the adjustable suture reduced the rate of complications after trabeculectomy. Conclusions: Currently, both ISGEO classification system and anterior chamber angle closure mechanism-based PACG classification system were adopted in the diagnosis and treatment of glaucoma. Low cerebrospinal fluid pressure as new risk factors for POAG has been widely acknowledged and given attentions by Chinese ophthalmologists. The 3-minute darkroom prone test and compound trabeculectomy with adjustable suture still need to be promoted. (Chin J Ophthalmol, 2017, 53: 115-120).

Splicing mutation of a gene within the Duchenne muscular dystrophy family.

The aim of this study was to identify the mutation site and phenotype of the Duchenne muscular dystrophy (DMD) gene in a DMD family. The DMD gene is by far the largest known gene in humans. Up to 34% of the point mutations reported to date affect splice sites of the DMD gene. However, no hotspot mutation has been reported. Capture sequencing of second-generation exons was used to investigate the DMD gene in a proband. Sanger sequencing was performed for mutation scanning in eight family members. Scale-invariant feature transform and PolyPhen were applied to predict the functional impact of protein mutations. A hemizygous splicing mutation IVS44ds +1G-A (c.6438 +1G>A) that induces abnormal splicing variants during late transcription and produces abnormal proteins was located in intron 44. Four missense mutations (p.Arg2937Gln, p.Asp882Gly, p.Lys2366Gln, and p.Arg1745His) that are known multiple-polymorphic sites were found in the coding region of the DMD gene. A heterozygous c.6438+1G>A mutation was detected on the X chromosome of the proband's mother and maternal grandmother.

Immunomodulatory effect of bone marrow mesenchymal stem cells on T lymphocytes in patients with decompensated liver cirrhosis.

We explored the immunomodulatory effects of bone marrow mesenchymal stem cells (BMSCs) on peripheral blood T lym-phocytes in patients with decompensation stage, hepatitis B-associated cirrhosis. MSCs from nine patients were analyzed by flow cytometry. Peripheral blood lymphocytes were isolated for fluorescent staining. Following stimulation by phytohemagglutinin (PHA), peripheral blood lymphocytes were co-cultured with BMSCs in serum and divided into four groups: (1) BMSC + lymphocyte + PHA contact culture group; (2) BMSC + lymphocyte + PHA non-contact culture group; (3) lym-phocyte + PHA positive control group; and (4) lymphocyte-only negative control group. Lymphocyte proliferation and frequencies of CD4(+)CD25(+)CD127(-) Tregs and CD4(+)CD8(-)IL-17(+) (Th17) cells were de-tected. Cell proliferation in groups 1 and 2 declined compared with group 3 (P < 0.01), and was notably higher than in group 4 (P < 0.01). CD4(+)CD25(+)CD127(-) Tregs frequencies in groups 1 and 2 were higher than in groups 3 and 4. In an intra-group comparison before and after culture, Th17 cell frequencies in groups 1 and 2 were higher than in group 4 (P < 0.01), but lower than in group 3 (P < 0.01). The Treg/Th17 ratio in groups 1 and 2 increased (P < 0.01), but did not change signifi-cantly in groups 3 and 4 (P > 0.05). In a comparison between groups after culture, the Treg/Th17 ratio in groups 1 and 2 increased more than in groups 3 and 4 (P < 0.01). BMSCs from cirrhotic patients can inhibit the proliferation of peripheral blood T lymphocytes, upregulate the ex-pression of CD4(+)CD25(+)CD127(-) Tregs, and improve Treg/Th17 imbal-ance. The mechanism by which this takes place may be associated with immunomodulatory effects induced by the secretion of soluble factors.

[Clinical characteristics and distribution of peripheral T lymphocyte subsets in patients with schistosomal hepatic diseases in Suzhou City].

OBJECTIVE: To investigate the clinical characteristics and the distribution of peripheral blood T lymphocyte sub-sets in patients with schistosomal hepatic cirrhosis in Suzhou City. METHODS: A total of 32 inpatients with liver diseases due to advanced schistosomiasis at the Department of Infectious Diseases, The First Affiliated Hospital of Soochow University from January 2016 to January 2018 were recruited and assigned into the infection and non-infection groups according to presence of co-infections, and 20 old healthy volunteers served as controls. Venous blood samples were collected on the day of admission, and the proportions of CD4+ T cells, CD8+ T cells, regulatory T (Treg) cells and Th17 cells were detected in peripheral blood using flow cytometry. RESULTS: Most patients with liver disorders due to advanced schistosomiasis were admitted to hospital in Suzhou City because of portal hypertension-associated complications, with a high prevalence of co-infections (59.38%, 19/32). The proportions of peripheral CD4+ and CD8+ T cells and Th17 cells were all significantly lower in patients with liver disorders due to advanced schistosomiasis than in controls (t = -5.111, -4.470 and -2.749, all P < 0.05), and a higher proportion of Treg cells was detected in patients than in controls (t = 5.628, P < 0.05). In addition, there were significant differences among the infection group, non-infection group and controls in terms of the percentage of CD4+ T cells, CD8+ T cells, Th17 cells and Treg cells (F = 15.837, 16.594, 9.290 and 27.866, all P < 0.05). CONCLUSIONS: Portal hypertension-associated complications are predominantly seen in patients with liver diseases due to advanced schistosomiasis at admission in Suzhou City, and co-infections are common. Imbalance of peripheral T cell subsets is detected in patients with liver diseases due to advanced schistosomiasis in Suzhou City.

The effectiveness of exercise programmes in patients with multiple myeloma: A literature review.

A limited number of clinical studies have investigated the effectiveness of participation in exercise training programmes for patients with multiple myeloma (MM), exploring the different biomedical, physical, psychological and quality of life. The aim of this literature review is to evaluate current quantitative and qualitative evidence concerning the effectiveness of participation in exercise programmes for patients with MM in improving physiological and/or psychological status. A literature search encompassing studies published between January 1998 and July 2013 was conducted through ten electronic databases. This search was further expanded through citation chaining, manual grey literature searches, and peer review consultation. In total, seven interventional studies were identified and appraised using Critical Appraisal Skill Programme (CASP) or Centre for Evidence-Based Management of Amsterdam (CEBMa). Though the majority of the studies presented encouraging data, however, three studies that implemented individualized exercise interventions for patients at different stages of MM and myeloablative treatment showed mixed results. In conclusion, the effectiveness of participation in exercise programmes remains unclear for patients with MM, as the studies reviewed were flawed by relatively weak methodological approaches.

Crystallization and preliminary crystallographic studies of trichomaglin, a novel ribosome-inactivating protein.

Trichomaglin, a novel ribosome-inactivating protein, has been crystallized in two crystal forms using the hanging-drop vapour-diffusion method. The form A and form B crystals belong to the orthorhombic space group P2(1)2(1)2(1) and the hexagonal space group P6(1) (or P6(5)), respectively. X-ray data have been collected to 3.3 and 2.2 A resolution for the form A and B crystals, respectively.

Crystal structure of recombinant trypsin-solubilized fragment of cytochrome b(5) and the structural comparison with Val61His mutant.

The crystal structure of the recombinant trypsin-solubilized fragment of the microsomal cytochrome b(5) from bovine liver has been determined at 1.9 A resolution and compared with the reported crystal structure of the lipase-solubilized fragment of the membrane protein cytochrome b(5). The two structures are similar to each other. However, some detailed structural differences are observed: the conformation of the segment Asn16-Ser20 is quite different, some helices around the heme and some segments between the helices are shifted slightly, the heme is rotated about the normal of the mean plane of heme, one of the propionates of the heme exhibits a different conformation. The average coordination distances between the iron and the two nitrogen atoms of the imidazole ligands are the same in the two structures. Most of the structural differences can be attributed to the different intermolecular interactions which result from the crystal packing. The wild-type protein structure is also compared with its Val61His mutant, showing that the heme binding and the main chain conformations are basically identical with each other except for the local area of the mutation site. However, when Val61 is mutated to histidine, the large side chain of His61 is forced to point away from the heme pocket toward the solvent region, disturbing the micro-environment of the heme pocket and influencing the stability and the redox potential of the protein.