Site-directed mutation of ß-galactosidase from Streptococcus thermophilus for galactooligosaccharide-enriched yogurt making.

ß-Galactosidase is one of the most important enzymes used in dairy processing. It converts lactose into glucose and galactose, and also catalyzes galactose to form galactooligosaccharides (GOS), so-called prebiotics. However, most of the ß-galactosidases from the starter cultures have low transgalactosylation activities, the process that results in galactose accumulation in yogurt. Here, a site-directed mutation strategy was attempted, to genetically modify ß-galactosidase from Streptococcus thermophilus. Out of 28 Strep. thermophilus strains, a ß-galactosidase gene named bgaQ, encoded for high ß-galactosidase hydrolysis activity (BgaQ), was cloned from the strain Strep. thermophilus SDMCC050237. It was 3,081 bp in size, with 1,027 deduced amino acid residuals, which belonged to the GH2 family. After replacing the Tyr801 and Pro802 around the active sites of BgaQ with His801 and Gly802, the GOS synthesis of the generated mutant protein BgaQ-8012 increased from 20.5% to 26.7% at 5% lactose, and no hydrolysis activity altered obviously. Subsequently, the purified BgaQ or BgaQ-8012 was added to sterilized milk inoculated with 2 starters from Strep. thermophilus SDMCC050237 and Lactobacillus delbrueckii ssp. bulgaricus ATCC11842. The GOS yields with added BgaQ or BgaQ-8012 increased to 5.8 and 8.3 g/L, respectively, compared with a yield of 3.7 g/L without enzymes added. Meanwhile, the addition of the BgaQ or BgaQ-8012 reduced the lactose content by 49.3% and 54.4% in the fermented yogurt and shortened the curd time. Therefore, this study provided a site-directed mutation strategy for improvement of the transgalactosylation activity of ß-galactosidase from Strep. thermophilus for GOS-enriched yogurt making.

[Female reproductive system dysplasia: a clinical study of 924 cases].

Objective: To explore the relationship between different types of female reproductive system dysplasia and age of visit, clinical manifestations, common types of combined malformations and endometriosis. Methods: The patient's medical records in the Second Hospital of Hebei Medical University from December 2002 to June 2016 were collected and retrospectively analyzed. Results: Among 924 cases of genital tract dysplasia, uterine dysplasia (65.3%, 824/1 261) was the most common, followed by vaginal dysplasia (28.3%, 357/1 261), hymen atresia and urogenital fistula (3.7%, 47/1 261), and cervical dysplasia (2.6%, 33/1 261). (1) The youngest age was in patients with hymen atresia and urogenital fistula, with a median of 14.5 years old, while the older age were in patients with uterine, vaginal and cervical dysplasia, with median age of 25.0, 24.0 and 23.0 years old, respectively. (2) The clinical manifestations were lack of specificity, mainly abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history. (3) About other systemic malformations, urological malformations were the most common (4.8%, 44/924), followed by spinal malformations (0.5%, 5/924), inguinal hernia (0.4%, 4/924), heart malformations (0.2%, 2/924), cleft lip and palate (0.2%, 2/924). Oblique vaginal septal syndrome and MRKH syndrome were the most likely to be associated with other system malformations. (4) About combination with endometriosis, there was no significant difference between obstructive genital tract malformations (2.3%, 9/385) and non obstructive genital tract malformations (1.7%, 9/539; P=0.469). Conclusions: Female reproductive system dysplasia is the most common in uterine dysplasia, followed by vaginal dysplasia, hymen atresia and urogenital fistula, and cervical dysplasia. The age of visit is generally older, often found by abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history;and could be combined with a variety of other system malformations, most seen by urinary system malformations,there is also the risk of endometriosis.

Genetic diversity and the conservation priority of Glycine soja populations from Northern China.

Knowledge of the spatial patterns of genetic variation in wild populations has significant implications for in situ conservation and the determination of conservation order. To study the levels of genetic diversity, spatial genetic structures, and genetic distances in Glycine soja, 11 natural populations in northern China were analyzed by estimating genetic coefficients using inter-simple sequence repeat (ISSR) fingerprints via mixed sampling strategies. Sixteen ISSR primers generated 98 reproducible polymorphic amplification banding patterns of 172 scored, accounting for 56.98% of the polymorphisms among the populations. The dendrogram based on Nei's genetic distance showed that distinct genetic differentiation occurred in G. soja. The Unweighted Pair-Group Method with Arithmetic Mean cluster analysis indicated two broad groups, and one contained all of the populations except three from Chengde, which formed the smaller second group. The spatial genetic structure evident in the wild soybean populations may be attributed to restricted seed dispersal and the dominant breeding system of this species. The detection of genetic structures in wild soybean populations could be a significant index for the effective conservation of many wild populations, and it could be exploited by soybean breeding programs to increase production.

[Clinical analysis of 18 children with aggressive mature B-cell lymphoma after liver transplantation].

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

[Emphasis on multidisciplinary collaboration in clinical diagnosis and treatment of autoimmune disease-related ulcers].

The global prevalence and incidence of autoimmune diseases are increasing year by year, and the autoimmune diseases have become a major threat to public health. In the progression of the diseases, persistent and complex abnormal immune responses often lead to long-term unhealed skin ulcers, which not only affect the life quality of patients, but also lead to the aggravation of primary diseases. Therefore, doctors in burn surgery and other wound repair surgeries should pay attention to the understanding of autoimmune diseases. In the treatment of autoimmune disease-related ulcers, it is recommended to formulate a unified treatment plan according to the law of occurrence and development of the diseases, and multidisciplinary cooperation is needed to accelerate wound healing and improve the quality of wound healing.

Data on the comprehensive first-principles diffusion study of the aluminum-magnesium system.

First-principles calculation of diffusion coefficients between Mg and Al is investigated comprehensively using density functional theory (DFT). The effect of different uncertainty sources arising from first principles calculations has been investigated systematically. These sources include the diffusion model, energetic, entropic and attempt frequency calculations. Variation in self and impurity diffusion coefficients of Mg and Al in stable phases are quantified using different DFT settings and compared with the experiments. Using the optimal DFT settings, diffusion coefficients in metastable phases of Al and Mg are predicted. The dataset refers to "An integrated experimental and computational study of diffusion and atomic mobility of the aluminum-magnesium system" [1].

Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer.

The histone methyltransferase DOT1L methylates lysine 79 (K79) on histone H3 and is involved in Mixed Lineage Leukemia (MLL) fusion leukemogenesis; however, its role in prostate cancer (PCa) is undefined. Here we show that DOT1L is overexpressed in PCa and is associated with poor outcome. Genetic and chemical inhibition of DOT1L selectively impaired the viability of androgen receptor (AR)-positive PCa cells and organoids, including castration-resistant and enzalutamide-resistant cells. The sensitivity of AR-positive cells is due to a distal K79 methylation-marked enhancer in the MYC gene bound by AR and DOT1L not present in AR-negative cells. DOT1L inhibition leads to reduced MYC expression and upregulation of MYC-regulated E3 ubiquitin ligases HECTD4 and MYCBP2, which promote AR and MYC degradation. This leads to further repression of MYC in a negative feed forward manner. Thus DOT1L selectively regulates the tumorigenicity of AR-positive prostate cancer cells and is a promising therapeutic target for PCa.

Risk factors of biliary complications following liver transplantation: retrospective analysis of a single centre.

BACKGROUND: Despite improvements that have been achieved in surgical techniques and organ preservation, biliary complications remain one of the most serious morbidities following liver transplantation. However, factors related to biliary complications after liver transplantation are not completely understood. The objective of this study was to identify retrospectively possible risk factors of biliary complications following liver transplantation. METHODS: Data on 279 patients who underwent liver transplantation between January 1999 and November 2005 were collected retrospectively. Selected variables from preoperative, intraoperative and postoperative data were first analysed using univariate logistic regression. Filtered factors with p<0.1 in the first step were further investigated to identify factors independently associated with biliary complications following liver transplantation. RESULTS: The overall incidence of biliary complications was 22.6%. Multivariate regression revealed that biliary cirrhosis (p = 0.038), anhepatic phase time (p = 0.04), and incidence of hepatic artery abnormality (p = 0.001) after transplantation were factors that were significantly related to biliary complications. Use of a T tube for biliary reconstruction and living grafts were not associated with biliary complications following liver transplantation. CONCLUSION: This study suggests that further technical refinement-namely, shortening the anhepatic phase duration, shielding the hepatic artery, and refining biliary duct reconstruction-can reduce the incidence of biliary complications following liver transplantation.

Identification, susceptibility, and detection of integron-gene cassettes of Arcanobacterium pyogenes in bovine endometritis.

The present study aimed to identify, determine the susceptibility, and detect gene cassettes of Arcanobacterium (Actinomyces) pyogenes isolates from cows with endometritis. Arcanobacterium pyogenes isolates were identified first by using the API Coryne Vit system test, and further through PCR. Minimum inhibitory concentrations of 23 antimicrobial agents against A. pyogenes were tested using standard broth microdilution assays according to the protocols of the Clinical and Laboratory Standards Institute. The genes of integrons I and II were amplified by PCR using specific primers. Thirty-two A. pyogenes isolates were isolated from 136 endometritic cows in the Hohhot region. Antibiotic susceptibility tests revealed that all isolates were highly sensitive to fluoroquinolones (100%), macrolides (approximately 81.2 to 100%) and florfenicol (90.6%), aminoglycosides (approximately 15.6 to 81.2%), and tetracyclines (approximately 43.7 to 68.7%). However, 53.1% were resistant to clindamycin, approximately 50 to 65.6% were resistant to penicillins, and approximately 37.5 to 71.9% were resistant to cephalosporins. One hundred percent were resistant to sulfonamides and bacitracin zinc. The integrons were further confirmed by sequencing. No class II integrons were detected, whereas 50% (n = 16) of the A. pyogenes isolates were positive for the presence of the intI I gene, but only 13 contained gene cassettes. Sequence analysis of gene cassettes revealed 6 gene cassettes, 4 of which encode resistant determinants of aminoglycosides (aadA1, aadA5, aadA24, and aadB) and 1 of which encodes the resistance gene of chloramphenicol (cmlA6). The function of the sixth identified cassette, designated ORF1, is unknown. The gene cassette arrays aadA24-ORF1, aadA5, and aadA1-addB-cmlA6 were found in 46.13% (6/13), 38.46% (5/13), and 38.46% (5/13) of the isolates, respectively. These cassettes segregated according to a consistent pattern, with aadA5 always alone, ORF1 always with aadA24, and aadA1-aadB and cmlA6 always together. Most of the positive integrons existed in the multiresistant isolates (n = approximately 3 to 7), indicating that the integrons played an important role in the dissemination and spread of antimicrobial resistance. This is the first report of A. pyogenes infections in dairy cows in China and of detection of gene cassettes and integrons in A. pyogenes.

Population dynamics of Echinops gmelinii Turcz. at different successional stages of biological soil crusts in a temperate desert in China.

The effects of biological soil crusts (BSC) on vascular plant growth can be positive, neutral or negative, and little information is available on the impacts of different BSC successional stages on vascular plant population dynamics. We analysed seedling emergence, survival, plant growth and reproduction in response to different BSC successional stages (i.e. habitats: bare soil, cyanobacteria, lichen and moss crusts) in natural populations of Echinops gmelinii Turcz. in the Tengger Desert of northwest China. The winter annual E. gmelinii is a dominant pioneer herb after sand stabilisation. During the early stages of BSC succession, the studied populations of E. gmelinii were characterised by high density, plant growth and fecundity. As the BSC succession proceeded beyond moss crusts, the fecundity decreased sharply, which limited seedling recruitment. Differences in seedling survival among the successional stages were not evident, indicating that BSC have little effect on survival in arid desert regions. Moreover, E. gmelinii biomass allocation exhibited low plasticity, and only reproductive allocation was sensitive to the various habitats. Our results further suggest that the negative effects of BSC succession on population dynamics are primarily driven by increasing topsoil water-holding capacity and decreasing rain water infiltration into deeper soil. We conclude that BSC succession drives population dynamics of E. gmelinii, primarily via its effect on soil moisture. The primary cause for E. gmelinii population decline during the moss-dominated stage of BSC succession is decreased fecundity of individual plants, with declining seed mass possibly reducing the success of seedling establishment.

Preliminary experience with indications for liver transplantation for hepatolithiasis.

OBJECTIVE: The aim of this study was to explore the indications for liver transplantation among patients with hepatolithiasis. PATIENTS AND METHODS: Data from 1,431 consecutive patients who underwent surgical treatment from January 2000 to December 2006 were retrospectively collected for analysis. Surgical procedures included T-tube insertion combined with intraoperative cholangioscopic removal of intrahepatic stones, hepatectomy, cholangiojejunostomy, and liver transplantation. RESULTS: Nine hundred sixty-one patients who had a stone located in the left or right intrahepatic duct underwent hepatectomy or T-tube insertion combined with intraoperative cholangioscopic removal of intrahepatic stones. The rate of residual stones was 7.5%. Four hundred seventy patients who had a stone located in the bilateral intrahepatic ducts underwent surgical procedures other than liver transplantation; the rate of residual stones was 21.7%. Only 15 patients with hepatolithiasis underwent liver transplantation; they all survived. According to the degree of biliary cirrhosis, recipients were divided into 2 groups: a group with biliary decompensated cirrhosis (n = 7), or group with compensated cirrhosis or no cirrhosis (n = 8). There were significant differences in operative times, transfusion volumes, and blood losses between the 2 groups (P < .05). In the first group, 6 of 7 patients experienced surgical complications, and in the second, 8 recipients recovered smoothly with no complications. Health status, disability, and psychological wellness of all recipients (n = 15) were significantly improved at 1 year after transplantation compared with pretransplantation (P < .05). CONCLUSIONS: Liver transplantation is a possible method to address hepatolithiasis and secondary decompensated biliary cirrhosis or difficult to remove, diffusely distributed intrahepatic duct stones unavailable by hepatectomy, cholangiojejunostomy, and choledochoscopy.

Estimation of standard liver volume for liver transplantation in the Chinese population.

INTRODUCTION: The accurate assessment of standard liver volume (SLV) is necessary for the safety of both the donor and the recipient in living donor liver transplantation. However, the accuracy of SLV formulas relates to cohorts or races. This study examined the accuracy of a simple linear formula versus previous formulas of SLV for Chinese adults. METHODS: Among 112 patients with normal liver, we created a new formula for SLV with stepwise regression analysis using the following variables: age, gender, body weight, body height, body mass index, and body surface area. The agreement between the actual liver volume (LV) and calculated LV using various formulas was prospectively evaluated among 63 living donors by paired-sample student's t-test and Lin's concordance correlation coefficient. RESULTS: A new formula was developed SLV (mL) = 949.7 x BSA (m(2)) - 48.3 x age - 247.4 where age was counted as 1 for those <40, 2 if 41-60, and 3 if >60 years old. The calculated LV using our formula showed no significant difference from the actual LV using the paired-samples student's t-test (P = .653). Lin's concordance correlation coefficient showed substantial agreement between estimated LV using our formula and actual LV. Furthermore, this study also observed an almost perfect agreement between our formula and the Yoshizumi et al formula. CONCLUSION: Our formula, which accurately estimated LV among Chinese adults, may be applicable to adults of other ethnicitis.

Surgical procedures for management of right portal venous branching in right lobe living donor liver transplantation.

OBJECTIVE: This study sought to describe the surgical management of right portal venous (PV) branches encountered among 104 cases of right lobe living donor liver transplantation (LDLT). METHODS: From January 2002 to September 2007, we performed 104 cases of right-lobe LDLT including 11-donors who had anomalous right portal venous branches (APVB). One recipient had PV sponginess hemangioma. The donor right PV branches were type I in 93 cases, type II (trifurcation) in nine cases, and type III in two cases. Except one narrow bridge of tissue excision, the PV branches were transected on the principal of donor priority: PV branches were excised approximately 2 to 3 mm from the confluence while leaving the donor's main portal vein and confluence intact. In type II APVB, donor PV branches were obtained with two separate openings in six cases; with two separate openings joined as a common orifice at the back table in two cases, with one common opening with a narrow bridge of tissue in one case. In type III APVB, the donor right anterior and posterior PV branches were obtained with separate openings. The donor right PV branches with one common opening in 92 cases of type I PV branches and a joined common orifice in three cases of type II APVB were anastomosed to the recipient's main portal vein or to right branching. As the unavailable recipient PV for sponginess hemangioma, one case of type I right PV branches was end-to-end anastomosed to one of the variceal lateral veins of about 1 cm diameter in a pediatric patient. The PV were reconstructed as double anastomoses in six type II APVB and in one type III APVB obtained with two separate PV openings. In the another type III APVB reconstruction, we successfully utilized a novel U-shaped vein graft interposition. RESULTS: The type II APVB donor receiving a narrow bridge of portal vein tissue excision developed portal vein thrombosis on the third postoperative day and underwent reexploration for thrombectomy. There were no vascular complications, such as portal vein thrombosis or stricture among other donors or all recipients. The velocity of blood flow in the U-graft was normal. The anastomosis between the type I donor right portal vein and recipient variceal lateral vein was unobstructed. CONCLUSION: Right PV branches should be excised on the principal of donor priority while leaving the donor's main portal vein and confluence intact. Single anastomoses was the fundamental procedure of right branch reconstruction. Double anastomoses could be used as the main management for type II and type III APVB reconstruction. U-graft interposition may be a potential procedure for type III APVB reconstruction. Single anastomoses between the donor right portal vein and the recipient variceal lateral vein may be performed when recipient portal vein is unavailable. These innovations for excision and reconstruction of right PV branches were feasible, safe, and had good outcomes.

University of California at San Francisco criteria can be applied to living donor liver transplantation for hepatocellular carcinoma: single-center preliminary results in 27 patients.

BACKGROUND: Living donor liver transplantation (LDLT) can provide life-saving therapy for many patients with hepatocellular carcinoma (HCC), who otherwise would succumb due to tumor progression. However, donor risk must be balanced against potential recipient benefit. METHODS: From January 2002 to December 2006, a total of 27 LDLT were performed for HCC patients in our center, including 25 right lobe grafts, and 2 dual grafts. Twenty-four (88.89%) met the University of California at San Francisco (UCSF) criteria, whereas 3 (11.11%) did not. RESULTS: Of our 29 donors, the overall complication rate was 17.24%. Two (6.90%) experienced major complications including intra-abdominal bleeding and portal vein thrombosis in 1, respectively; 3 (10.34%) experienced minor complications: wound steatosis, pleural effusion, and transient chyle leakage in 1, respectively. We did not observe any donor mortality; all donors fully recovered and returned to their previous occupations. No recipient developed small-for-size syndrome. The overall HCC patient survival rates at 1- and 3-years were 84.01% and 71.40%, respectively, similar to those of patients undergoing LDLT for various nonmalignant diseases during the same period (P > .05). CONCLUSIONS: Although further study is needed to fully assess the risks and benefits of LDLT for both HCC patients and donors, our preliminary results suggested that LDLT offered an acceptable chance and duration of survival for HCC patients. It was not only a relatively safe procedure provided that every effort was taken to minimize donor morbidities, but also beneficial for HCC recipients.

Arterial complications after living-related liver transplantation: single-center experience from West China.

Vascular complications after liver transplantation remain a major source of morbidity and mortality for recipients. In particular, patients receiving living-related liver transplantation (LRLT) experience a higher rate of vascular complications owing to the complex vascular reconstruction. Between July 2001 and December 2005, LRLTs were performed in our center on 33 patients with end-stage liver diseases. The 23 men and 10 women had a mean age of 32.6 +/- 11.3 years (range = 5 to 58 years). Of the 33 patients, the percentage of vascular complications was 9.09% (3 cases), including hepatic arterial thrombosis (HAT), hepatic arterial stenosis (HAS), or hepatic artery pseudoaneurysm (HAP) in one patient, respectively. No portal vein or hepatic vein complication occurred in our patients. Thrombectomy was performed in the patient with thrombosis. The patient with stenosis was treated with balloon angioplasty and endoluminal stent placement. The pseudoaneurysm was also successfully embolized to restore the blood flow toward the donor liver. Mean follow-up for all patients after LRLT was 18.0 +/- 5.4 months. The overall postoperative 30-day mortality rate was 6.06% (2/33). The 1-year survival rate was 86.36% in 22 patients with benign diseases and 72.73% in 11 patients with malignant diseases. However, no death was associated with vascular complications. Careful preoperative evaluation and intraoperative microsurgical technique for hepatic artery reconstructions are the keys to prevent vascular complications following LRLT. Immediate surgical intervention is required for acute vascular complications, whereas late complications may be treated by balloon angioplasty and endoluminal stent placement. Embolization may be a safe and effective approach in the treatment of a pseudoaneurysm of the hepatic artery.

[Study on the super-antigen genes of group A Streptococcus pyogenes strains isolated from patients with scarlet fever and pharyngeal infection, in Beijing, 2015-2017].

Objective: To analyze the characteristics of super-antigen (SAg) of group A Streptococcus pyogenes (GAS), isolated from patients with scarlet fever or pharyngeal infections in Beijing between 2015-2017. Methods: Throat swab specimens from patients with scarlet fever or pharyngeal infections were collected and tested for GAS. Eleven currently known SAg genes including SpeA, speC, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were tested by real-time PCR while M protein genes (emm genes) were amplified and sequenced by PCR. Results: A total of 377 GAS were isolated from 6 801 throat swab specimens, with the positive rate as 5.5%. There were obvious changes noticed among speC, speG, speH and speK in three years. A total of 45 SAg genes profiles were observed, according to the SAgs inclusion. There were significant differences appeared in the frequencies among two of the highest SAg genes profiles between emm1 and emm12 strains (χ(2)=38.196, P<0.001; χ(2)=72.310, P<0.001). There also appeared significant differences in the frequencies of speA, speH, speI and speJ between emm1 and emm12 strains (χ(2)=146.154, P<0.001; χ(2)=52.31, P<0.001; χ(2)=58.43, P<0.001; χ(2)=144.70, P<0.001). Conclusions: Obvious changes were noticed among SAg genes including speC, speG, speH and speK from patients with scarlet fever or pharyngeal infections in Beijing between 2015-2017. SAg genes including speA, speH, speI and speJ appeared to be associated with the emm 1 and emm 12 strains. More kinds of SAg genes profiles were isolated form GAS but with no significant differences seen in the main SAg genes profiles, during the epidemic period.

Safety of donor in adult-to-adult living donor liver transplantation using right lobe graft.

BACKGROUND: The growing gap between the number of patients awaiting liver transplantation and available organs has continued to be the primary issue facing the transplant community. To overcome the waiting list mortality, living donor liver transplantation has become an option, in which the greatest concern is the safety of the donor, especially in adult-to-adult living donor liver transplantation (A-A LDLT) using a right lobe liver graft. OBJECTIVE: We evaluated the safety of donors after right lobe liver donation for A-A LDLT performed in our center. METHODS: From January 2002 to March 2006, 26 patients underwent A-A LDLT using right lobe liver grafts in our center. Seven donors were men and 19 were women (range, 19-65 years; median age, 38 years). The right lobe liver grafts were obtained by transecting the liver on the right side of the middle hepatic vein without interrupting the vascular blood flow. The mean follow-up time for these donors was 9 months. RESULTS: These donor residual liver volumes ranged from 30.5% to 60.3%. We did not experience any donor mortality. Two cases (7.69%) experienced major complications: intra-abdominal bleeding and portal vein thrombosis in one each and three (11.54%), minor ones: wound steatosis in two, and transient chyle leak in one. All donors were fully recovered and returned to their previous occupations. CONCLUSIONS: A-A LDLT using a right lobe liver graft has become a standard option. The donation of right lobe liver for A-A LDLT was a relatively safe procedure in our center.

FOXA1 inhibits prostate cancer neuroendocrine differentiation.

Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression. Further, IL-8 upregulation activates the MAPK/ERK pathway, leading to ERK phosphorylation and enolase 2 (ENO2) expression. IL-8 knockdown or ERK inhibition, on the other hand, abolished FOXA1 loss-induced NE differentiation. Analysis of xenograft mouse models confirmed FOXA1 loss in NEPC tumors relative to its adenocarcinoma counterparts. Importantly, FOXA1 is downregulated in human NEPC tumors compared to primary and castration-resistant prostate cancers, and its expression is negatively correlated with that of ENO2. These findings indicate that FOXA1 transcriptionally suppresses IL-8, the expression of which would otherwise stimulate the MAPK/ERK pathway to promote NE differentiation of prostate cancer cells. Our data strongly suggest that FOXA1 loss may play a significant role in enabling prostate cancer progression to NEPC, whereas IL-8 and MAPK/ERK pathways may be promising targets for therapeutic intervention.

PKK deficiency in B cells prevents lupus development in Sle lupus mice.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B-lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model. We demonstrate that the conditional deletion of PKK in B cells prevents lupus development in Sle1Sle3 mice. The loss of PKK in Sle mice resulted in the amelioration of multiple classical lupus-associated phenotypes and histologic features of lupus nephritis, including marked reduction in the levels of serum autoantibodies, proteinuria, spleen size, peritoneal B-1 cell population and the number of activated CD4 T cells. In addition, the abundance of autoreactive plasma cells normally seen in Sle lupus mice was also significantly decreased in the PKK-deficient Sle mice. Sle B cells deficient in PKK display defective proliferation responses to BCR and LPS stimulation. Consistently, B cell receptor-mediated NF-κB activation, which is required for the survival of activated B cells, was impaired in the PKK-deficient B cells. Taken together, our work uncovers a critical role of PKK in lupus development and suggests that targeting the PKK-mediated pathway may represent a promising therapeutic strategy for lupus treatment.

Postoperative severe pneumonia in adult liver transplant recipients.

Severe pneumonia in adult liver transplantation (OLT) recipients is a dangerous condition with significant morbidity and mortality. To analyze the risk factors for postoperative severe pneumonia in OLT patients, we collected data from 132 consecutive adult patients who underwent OLT between February 1999 and April 2004. According to the American Thoracic Society consensus statement, episodes of severe pneumonia were observed in 24 patients (18.2%). We retrospectively reviewed the etiology diagnosis, treatment, and prognosis of the 24 recipients. Bacteria were responsible for 95.8% of these episodes (23 of 24), fungi for 16.7% (4 of 24) and viruses for 4.4% (1 of 24). Twenty-six percent of the bacterial pneumonias were due to Streptococcus alpha hemolyticus. The mortality rate was 37.5% (9 of 24) for patients with severe pneumonia versus 7.4% (8 of 108, P = .004) for patients without pneumonia. Two cases with hepatorenal syndrome died, and three patients with coinfection by bacteria and fungi died. Acute rejection episodes occurred in 15 patients, four of whom died. Mechanical ventilation and tracheotomy were required in 13 cases (54%). Six who experienced prolonged intubation died. Sputum and pleural fluid cultures helped to establish a diagnosis in 91.7% (22 of 24) of cases. Twenty cases (83%) underwent reduction in the immunosuppressive regimen. Patient age, intraoperative transfusion requirements, extubation time, and hospital stay were fatal predictors of prognoses. We concluded that early detection of the responsible pathogen; timely and specific diagnosis; reduction in the immunosuppressive regimen; appropriate treatment with reliable, effective techniques; and implementation of sensitive culture-based antibiotics was an effective strategy to treat severe adult pneumonia in liver transplantation recipients.