[The prognostic value of the international prognostic index, the national comprehensive cancer network IPI and the age-adjusted IPI in diffuse large B cell lymphoma].

Objective: To explore the prognostic value of the international prognostic index (IPI), the national comprehensive cancer network IPI(NCCN-IPI)and the age-adjusted IPI (aa-IPI) in diffuse large B cell lymphoma. Methods: A total of 311 patients with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2003 to 2012 in Nanfang hospital were included. All patients were divided into CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) and R-CHOP (rituximab, CHOP) groups. Survival analysis was compared among IPI, NCCN-IPI and aa-IPI models. Discrimination of three different prognostic models was assessed using the Harrell's C statistic. Results: A total of 311 patients were analyzed. Among them, 128 patients were treated with CHOP regimen and other 183 patients were treated with R-CHOP regimen. In CHOP groups, both NCCN-IPI (5-year OS: 59.7% vs 26.8%, P<0.001) and aa-IPI (5-year OS: 71.0% vs 25.0%, P<0.001) showed better risk stratification for low-intermediate and high-intermediate group than the IPI (5-year OS: 47.6% vs 36.6%, P=0.003). However, in the patients treated with R-CHOP, NCCN-IPI showed better risk stratification in low, low-intermediate, high-intermediate groups (5-year OS: 96.0% vs 83.0% vs 66.5%, P=0.009). According to the Harrell's C statistic, C-index of IPI, NCCN-IPI and aa-IPI for overall survival (OS) were 0.546, 0.667, 0.698 in CHOP group and 0.611,0.654, 0.695 in R-CHOP group respectively. In patients younger than 60 years old, C-index of IPI, NCCN-IPI and aa-IPI for OS were 0.534, 0.675, 0.698 in CHOP group and 0.584, 0.648, 0.695 in R-CHOP respectively. Conclusion: The NCCN-IPI is more powerful than IPI and aa-IPI in DLBCL patients receiving R-CHOP. aa-IPI is a preferable model in predicting prognosis than IPI and NCCN-IPI in anthracycline-based chemotherapy without rituximab.

[An efficacy and safety study of bifidobacterium tetragenous viable bacteria tablets in the treatment of constipation in patients with type 2 diabetes mellitus].

Objective: The incidence of gastrointestinal symptoms in diabetes is higher than that of non-diabetes. Thus, the aim of the present study was to observe the efficacy and safety of bifidobacterium tetragenous viable bacteria tablets in the treatment of constipation in patients with type 2 diabetes mellitus. Methods: This is a multicenter, randomized, double-blind, placebo-controlled, parallel group-comparison clinical research. The subjects were randomly divided into study group and control group according to 1∶1 ratio by computer generated random number method. The subjects were either treated with bifidobacterium tetragenous viable bacteria tablets (study group) or placebo (control group) for eight weeks, and they were followed up for four weeks without changing foundation therapy for diabetes. The primary outcome was the change of complete spontaneous bowel movements (CSBMs). Results: A total of 234 subjects (the study group:116 cases; the control group: 118 cases) from 7 centers were included in the present study. The baseline characteristics were comparable between the two groups. In the study group, the CSBMs at 0, 2, 4, 8 and 12 weeks were 0.0 (0.0, 1.0) , 1.0 (0.5, 2.0) , 2.0 (1.0, 3.0) , 3.0 (2.0, 3.5) , 2.0 (1.0, 3.0) times per week, respectively, while the CSBMs of the control group at each corresponding weeks were 0.0 (0.0, 1.0) , 1.0 (0.0, 1.5) , 1.0 (0.0, 1.5) , 1.0 (0.0, 2.0) , 1.0 (0.0, 1.5) times per week, respectively. There is significant difference in CSBMs between the two groups (P<0.05). Moreover, after 12 weeks treatment, the CSBMs over spontaneous bowel movements (SBMs) ratio in the study group was higher than that in the control group [0.53 (0.40, 0.67) vs 0.33 (0.00,0.50), P=0.048], indicating a more complete evacuation sensation in the study group. More subjects in the study group (66.38%) reached Bristol stool classification of normal criteria than those in the control group (48.31%, P=0.005). There were significantly improvement of bowel function index in the study group [study group 42.7 (33.3, 56.7), control group 60.6 (51.7, 75.7), P<0.000 1]. Furthermore, the symptoms of constipation was improved, and the satisfaction for the treatment was high in the study group. There were no significant differences of the safety indicators between the two groups. Conclusions: Bifidobacterium tetragenous viable bacteria tablets can be used in patients with type 2 diabetes mellitus and constipation. Compared with placebo, it improves constipation and has no obvious adverse effects.

Does murine spermatogenesis require WNT signalling? A lesson from Gpr177 conditional knockout mouse models.

Wingless-related MMTV integration site (WNT) proteins and several other components of the WNT signalling pathway are expressed in the murine testes. However, mice mutant for WNT signalling effector ß-catenin using different Cre drivers have phenotypes that are inconsistent with each other. The complexity and overlapping expression of WNT signalling cascades have prevented researchers from dissecting their function in spermatogenesis. Depletion of the Gpr177 gene (the mouse orthologue of Drosophila Wntless), which is required for the secretion of various WNTs, makes it possible to genetically dissect the overall effect of WNTs in testis development. In this study, the Gpr177 gene was conditionally depleted in germ cells (Gpr177(flox/flox), Mvh-Cre; Gpr177(flox/flox), Stra8-Cre) and Sertoli cells (Gpr177(flox/flox), Amh-Cre). No obvious defects in fertility and spermatogenesis were observed in these three Gpr177 conditional knockout (cKO) mice at 8 weeks. However, late-onset testicular atrophy and fertility decline in two germ cell-specific Gpr177 deletion mice were noted at 8 months. In contrast, we did not observe any abnormalities of spermatogenesis and fertility, even in 8-month-old Gpr177(flox/flox), Amh-Cre mice. Elevation of reactive oxygen species (ROS) was detected in Gpr177 cKO germ cells and Sertoli cells and exhibited an age-dependent manner. However, significant increase in the activity of Caspase 3 was only observed in germ cells from 8-month-old germ cell-specific Gpr177 knockout mice. In conclusion, GPR177 in Sertoli cells had no apparent influence on spermatogenesis, whereas loss of GPR177 in germ cells disrupted spermatogenesis in an age-dependent manner via elevating ROS levels and triggering germ cell apoptosis.

Sodium-hydrogen exchanger NHA1 and NHA2 control sperm motility and male fertility.

Our previous work identified NHA1, a testis-specific sodium-hydrogen exchanger, is specifically localized on the principal piece of mouse sperm flagellum. Our subsequent study suggested that the number of newborns and fertility rate of NHA1-vaccinated female mice are significantly stepped down. In order to define the physiological function of NHA1 in spermatozoa, we generated Nha1(Fx/Fx), Zp3-Cre (hereafter called Nha1 cKO) mice and found that Nha1 cKO males were viable and subfertile with reduced sperm motility. Notably, cyclic AMP (cAMP) synthesis by soluble adenylyl cyclase (sAC) was attenuated in Nha1 cKO spermatozoa and cAMP analogs restored sperm motility. Similar to Nha1 cKO males, Nha2(Fx/Fx), Zp3-Cre (hereafter called Nha2 cKO) male mice were subfertile, indicating these two Nha genes may be functionally redundant. Furthermore, we demonstrated that male mice lacking Nha1 and Nha2 genes (hereafter called Nha1/2 dKO mice) were completely infertile, with severely diminished sperm motility owing to attenuated sAC-cAMP signaling. Importantly, principal piece distribution of NHA1 in spermatozoa are phylogenetically conserved in spermatogenesis. Collectively, our data revealed that NHA1 and NHA2 function as a key sodium-hydrogen exchanger responsible for sperm motility after leaving the cauda epididymidis.

Application of slightly acidic electrolyzed water for inactivating microbes in a layer breeding house.

Lots of microorganisms exist in layer houses can cause bird diseases and worker health concerns. Spraying chemical disinfectants is an effective way to decontaminate pathogenic microorganisms in the air and on surfaces in poultry houses. Slightly acidic electrolyzed water (SAEW, pH 5.0-6.5) is an ideal, environmentally friendly broad-spectrum disinfectant to prevent and control bacterial or viral infection in layer farms. The purpose of this work was to investigate the cleaning effectiveness of SAEW for inactivating the microbes in layer houses. The effect of SAEW was evaluated by solid materials and surface disinfection in a hen house. Results indicate that SAEW with an available chlorine concentration of 250 mg/L, pH value of 6.19, and oxygen reduction potential of 974 mV inactivated 100% of bacteria and fungi in solid materials (dusts, feces, feather, and feed), which is more efficient than common chemical disinfectant such as benzalkonium chloride solution (1:1,000 vol/vol) and povidone-iodine solution (1:1,000 vol/vol). Also, it significantly reduced the microbes on the equipment or facility surfaces (P < 0.05), including floor, wall, feed trough, and water pipe surfaces. Moreover, SAEW effectively decreased the survival rates of Salmonella and Escherichia coli by 21 and 16 percentage points. In addition, spraying the target with tap water before disinfection plays an important role in spray disinfection.

Disinfection effectiveness of slightly acidic electrolysed water in swine barns.

AIMS: To evaluate the disinfection effectiveness of slightly acidic electrolysed water (SAEW, pH 6·25-6·53), a new environmental friendly agent for inactivating micro-organisms adhered to the facility and aerosolized in the air of the swine barns and to explore the application of SAEW in livestock industries. METHODS AND RESULTS: Bacteria and fungi were isolated from the swine house air and treated by SAEW. The SAEW solution was flushed onto surfaces and sprayed within the whole swine barn. SAEW with an available chlorine concentration (ACC) of 300 mg l(-1) can inhibit isolated microbes completely. The usage of SAEW (300 mg l(-1) ) resulted in a significant (P < 0·05) reduction in microbes on the wall, rail and floor after flushing disinfection. Additionally, spraying SAEW at an ACC of 300 mg l(-1) reduced 59% of the airborne organisms in 30 min and kept the population of microbes at a reduced level for at least 8 h. SAEW treatment also reduced pathogens on surfaces (P < 0·03) after spraying disinfection except on the surface of the wall. CONCLUSIONS: SAEW may be a potential alternative disinfectant to reduce infections in swine barns. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study provide information on the antimicrobial efficiency of SAEW on the airborne bacteria and fungi in swine barns.