[Prediction on the cardio-cerebrovascular death and probability of premature death caused by common risk factors in China in 2030].

Objective: Predictive models were used to evaluate the impact of common risk factors on the number of cardio-cerebrovascular deaths and the probability of premature death. Methods: Using the data for China estimated by the Global Burden of Disease study 2015 (GBD 2015), we calculated the population attribution fraction (PAF) of risk factors. The proportional change model was used to estimate the number of unattributable deaths by 2030, and to predict the number of deaths, mortality, standardized mortality and probability of premature death by 2030. Results: According to the natural change trend of risk factors from 1990 to 2015, the number of deaths and mortality would reach 6.12 million and 428.53/100 000 by 2030, with an increase of 59.92% and 52.87%. By 2030, the probability of premature death from cardio-cerebrovascular diseases among Chinese aged 30-70 years old would continue to decline, from 11.43% to 11.28% for men, and from 5.79% to 4.43% for women. If the goals of all included risk factors were reached by 2030, 2 289 200 cardio-cerebrovascular deaths would be avoided. If only the exposure to a single risk factor was achieved by 2030, blood pressure, total cholesterol, and fine particulate matter exposure were the three most important factors affecting cardio-cerebrovascular deaths, which would reduce 1 332 800, 609 100 and 306 800 deaths, respectively. Among the involved risk factors, the control of blood pressure would mostly decrease the number of deaths due to ischemic heart disease and hemorrhagic stroke, about 677 300 and 391 100 deaths, accordingly. Conclusion: The control of risk factors is of great significance in reducing deaths and probability of premature death due to cardio-cerebrovascular diseases. If the control targets of all risk factors could be achieved by 2030, the burden of cardio-cerebrovascular diseases would be reduced greatly.

Efficient androst-1,4-diene-3,17-dione production by co-expressing 3-ketosteroid-Δ1 -dehydrogenase and catalase in Bacillus subtilis.

AIMS: 3-ketosteroid-Δ1 -dehydrogenase (KSDD), a flavin adenine dinucleotide (FAD)-dependent enzyme involved in sterol metabolism, specifically catalyses the conversion of androst-4-ene-3,17-dione (AD) to androst-1,4-diene-3,17-dione (ADD). However, the low KSDD activity and the toxic effects of hydrogen peroxide (H2 O2 ) generated during the biotransformation of AD to ADD with FAD regeneration hinder its application on AD conversion. The aim of this work was to improve KSDD activity and eliminate the toxic effects of the generated H2 O2 to enhance ADD production. METHODS AND RESULTS: The ksdd gene obtained from Mycobacterium neoaurum JC-12 was codon-optimized to increase its expression level in Bacillus subtilis, and the KSDD activity reached 12·3 U mg-1 , which was sevenfold of that of codon-unoptimized gene. To improve AD conversion, catalase was co-expressed with KSDD in B. subtilis 168/pMA5-ksddopt -katA to eliminate the toxic effects of H2 O2 generated during AD conversion. Finally, under optimized bioconversion conditions, fed-batch strategy was carried out and the ADD yield improved to 8·76 g l-1 . CONCLUSIONS: This work demonstrates the potential to improve enzyme activity by codon-optimization and eliminate the toxic effects of H2 O2 by co-expressing catalase. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed the highest ADD productivity ever reported and provides a promising strain for efficient ADD production in the pharmaceutical industry.

Identification and characterization of a novel 2,3-butanediol dehydrogenase/acetoin reductase from Corynebacterium crenatum SYPA5-5.

UNLABELLED: Acetoin and 2,3-butanediol are widely used in the chemical and pharmaceutical industries. The enzyme, 2,3-butanediol dehydrogenase/acetoin reductase (2,3-BDH/AR), plays a significant role in the microbial production of acetoin and 2,3-butanediol by catalysing a reversible reaction between acetoin and 2,3-butanediol. To date, a 2,3-BDH has not been characterized from Corynebacterium crenatum. 2,3-BDH was cloned from Coryne. crenatum SYPA5-5 and expressed in Escherichia coli BL21. Sequence analysis suggested that the 2,3-BDH from Coryne. crenatum SYPA5-5 belongs to the short-chain dehydrogenase/reductase superfamily. Its maximum specific activity was obtained at 35°C, however, it became very unstable when the temperature was above 35°C. Its optimal pH was 4·0 for reduction reaction and 10·0 for oxidation reaction. The 2,3-BDH activity was increased to some extent by Ca(2+) , Mg(2+) , Zn(2+) and Mn(2+) ions. In particular, Ca(2+) induced about 1·5-fold increase. The value of kcat /Km for diacetyl and acetoin are higher than for 2,3-butanediol indicating that 2,3-BDH can easily reduce diacetyl or acetoin to 2,3-butanediol under lower pH conditions. The characteristics of 2,3-BDH from Coryne. crenatum SYPA5-5 will give guide to further studies for the production of acetoin and 2,3-butanediol with engineered Coryne. crenatum SYPA5-5. SIGNIFICANCE AND IMPACT OF THE STUDY: Acetoin and 2,3-butanediol are commonly used as platform chemicals and widely used in pharmaceutical industries. 2,3-butanediol dehydrogenase/acetoin reductase (2,3-BDH/AR) plays a significant role in the microbial production of acetoin and 2,3-butanediol. In this study, 2,3-BDH was cloned from Corynebacterium crenatum SYPA5-5, was expressed in Escherichia coli BL21 and characterized with respect to the optimal temperature, pH, substrate specificity and kinetics. The results will guide further studies in Coryne. crenatum SYPA5-5 for the production of acetoin and 2,3-butanediol.

Short-term therapeutic drug monitoring of mycophenolic acid reduces infection: a prospective, single-center cohort study in Chinese living-related kidney transplantation.

BACKGROUND: The role of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in kidney transplant recipients (KTRs) is not clear. We performed a prospective cohort study to evaluate the efficiency of MPA TDM in the Chinese population. METHODS: A total of 183 living-related KTRs were studied; 101 KTRs received controlled-dose mycophenolate mofetil (MMF) (the CD group), and 82 patients received fixed-dose MMF (the FD group). MPA exposure was measured at days 3, 7, 14, and 30 in the CD group, and at day 30 in the FD group. The primary endpoint was treatment failure (a composite of acute rejection, graft loss, death, or MMF discontinuation) at 12 months post transplantation. RESULTS: In the CD group, with a starting MMF dose of 2 g/day, approximately 35% of patients had high MPA levels, which were >60 mg × h/L, and mean MPA levels were 59.17 mg × h/L and 61.38 mg × h/L for the CD and FD groups, respectively (P = 0.588). After adjusting MMF dose, MPA exposures in the CD group at day 30 were lower than those in the FD group at day 30 (54.06 vs. 61.38, P = 0.004). At month 12, the CD group had fewer infections (16.8% vs. 31.7%, P = 0.018) with no difference in treatment failure, acute rejection, diarrhea, or anemia. CONCLUSIONS: KTRs can benefit from short-term TDM of MPA in reducing infection, without increasing acute rejection.

[Enhancing survival outcomes in stage â ¢ gastric/esophagogastric junction cancer: a retrospective study of immune checkpoint inhibitors and adjuvant chemotherapy based on real-world data].

Objective: To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer. Methods: This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results: The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference (P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion: Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.

Molecular surveillance based on anaplasmosis in domestic small ruminants: First report on zoonotic Anaplasma capra and phylogenetic insights from Faisalabad, Pakistan.

Anaplasma is an intracellular alphaproteobacteria that infects diverse blood cell types in animal hosts including small ruminants. Epidemiological and risk factors information on zoonotic anaplasmosis with respect to anaplasmosis in sheep and goats are scarce. Therefore, the objective of the current study was to estimate the prevalence, risk factors of anaplasmosis and phylogenetic investigation of A. capra in sheep and goats from Faisalabad district, Pakistan. Briefly, 384 blood samples were randomly collected from sheep and goats of Faisalabad district, Pakistan, during January to May 2022. The samples were processed for the detection of Anaplasma targeting 16S rRNA gene using PCR. The data regarding disease determinants were collected using a predesigned questionnaire. Out of 384 samples, 131 samples were found positive for Anaplasma spp. with a prevalence rate of 34.11%. The results indicated a significantly higher prevalence of anaplasmosis in goats (41.88%) compared to sheep (22.00%). In addition, the chi square indicated that housing type, tick infestation, gender, tick control practices, age, mix farming, and hygiene were significantly associated with the occurrence of disease. The analysis of multivariate logistic regression expressed gender as the significant risk factor (p = 0.0001, OR = 1.757, CI = 1.305-2.366). The acquired sequences revealed four novel isolates of A. capra (Genbank accession numbers ON834323, ON838209, ON838210, and ON838211). The phylogenetic analysis of the 16S rRNA gene of A. capra revealed three distinct clusters with 99-100% homology with other isolates from different countries. Our isolates showed higher similarity with isolates from China (KM206273, KP314237, MT799937), Pakistan (ON238129, ON238130, ON238131), Angola (MT898988), India (MZ558066), Iran (MW692362), and Turkey (MT632469) isolated from human, sheep, ticks, goats, cattle, Gaddi goat, Persian Onager (Equus hemionus onager), and Turkish goats, respectively. In conclusion, A. capra is endemic in Punjab, Pakistan, there is a need to conduct large scale surveillance studies to assess the status of this pathogen at human-animal interface as well as to develop effective preventive and control strategies to reduce the economic losses associated with anaplasmosis in small ruminants.

Clinicopathological and prognostic significance of α5ß1-integrin and MMP-14 expressions in colorectal cancer.

The purpose of this study was to evaluate the association of expression level of α5ß1-integrin and MMP-14 with clinicopathologic features and prognosis in colorectal cancer (CRC). The expressions of α5ß1-integrin and MMP-14 in normal colorectal mucosa and CRC tissue were detected with immunohistochemistry. We estimated the five-year survival rate by the Kaplan-Meier method. The positive expressions rates of α5ß1-integrin and MMP-14 in CRC tissue were 60.6% and 63.3% respectively, and there were significant differences on their positive expression rates between in CRC tissue and in normal colorectal mucosa(P<0.05). The expression rates of α5ß1-integrin and MMP-14 in patients with poor histological differentiation, lymph node metastasis and high clinical staging were heightened. There was a significant difference (P<0.05) on the five-year survival rate for α5ß1-integrin expression, which was 44.6% in positive groups and 75.5% in negative groups. And there was a significant difference (P<0.05) on the five-year survival rate for MMP-14 expression, which was 48.2% in positive group and 73.1% in negative group. The expression of α5ß1-integrin and MMP-14 is correlated with the progression and metastasis of CRC, and α5ß1-integrin and MMP-14 may be used as prognostic markers in CRC.

Non-Hermitian control between absorption and transparency in perfect zero-reflection magnonics.

Recent works in metamaterials and transformation optics have demonstrated exotic properties in a number of open systems, including perfect absorption/transmission, electromagnetically induced transparency, cloaking or invisibility, etc. Meanwhile, non-Hermitian physics framework has been developed to describe the properties of open systems, however, most works related to this focus on the eigenstate properties with less attention paid to the reflection characteristics in complex frequency plane, despite the usefulness of zero-reflection (ZR) for applications. Here we demonstrate that the indirectly coupled two-magnon system not only exhibits non-Hermitian eigenmode hybridization, but also ZR states in complex frequency plane. The observed perfect-ZR (PZR) state, i.e., ZR with pure real frequency, is manifested as infinitely narrow reflection dips (~67 dB) with infinite group delay discontinuity. This reflection singularity of PZR distinguishes from the resonant eigenstates but can be adjusted on or off resonance with the eigenstates. Accordingly, the absorption and transmission can be flexibly tuned from nearly full absorption (NFA) to nearly full transmission (NFT) regions.

[Forecasting the burden of disease from diabetes under the scenarios of specific risk factors control in China in 2030].

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.

Anticoccidial activity of herbal complex in broiler chickens challenged with Eimeria tenella.

The objective of the present study was to evaluate the anticoccidial effect of different concentrations of the herbal complex of 4 plants (leaves of Azadirachta indica and Nicotiana tabacum, flowers of Calotropis procera and seeds of Trachyspermum ammi) in broiler chickens in comparison with amprolium anticoccidial. Three concentrations (2 g, 4 g and 6 g) of herbal complex were given to the experimental groups once a day and amprolium (at the dose rate of 125 ppm) was given orally in drinking water from the 14th to the 21st days of age. One group was kept as infected, non-medicated control and one as non-infected, non-medicated control. All groups were inoculated orally with 75,000 sporulated oocysts on the 14th day of age except the non-infected, non-medicated control. Among herbal complex medicated groups, the maximum anticoccidial effect was seen in the group medicated with 6 g herbal complex followed by 4 g and 2 g herbal complex medicated groups. Treatment with 6 g of the herbal complex significantly reduced the negative performance and pathogenic effects associated with Eimeria tenella challenge at a level that was comparable with amprolium when using a largely susceptible recent field isolate. In summary, concentration-dependent anticoccidial activity of the studied herbal complex suggests its use as an alternative anticoccidial agent to chemotherapeutic drugs for Eimeria tenella control.

Ubiquitin pathway and ovarian cancer.

The ubiquitin-proteasome pathway is a common cellular process in eukaryotic tissue. Ubiquitin binds to proteins and tags them for destruction; this tagging directs proteins to the proteosome in the cell that degrades and recycles unneeded proteins. The ubiquitin-proteasome pathway plays an important role in the regulation of cellular proteins with respect to cell cycle control, transcription, apoptosis, cell adhesion, angiogenesis, and tumour growth. This review article discusses the various ways that the ubiquitin pathway is involved in ovarian cancer, such as modulating the ovarian-cancer-related gene BRCA1 and tumour suppressor p53, and interfering with the erk pathway, the cyclin-dependent cell cycle regulation process, and ERBB2 gene expression.

[Prediction on the burden of disease of chronic obstructive pulmonary disease and simulation of the effectiveness of controlling risk factors in China by 2030].

Objective: To forecast the burden of chronic obstructive pulmonary disease (COPD) in China by 2030 and evaluate the effectiveness of controlling risk factors based on the predictive model. Methods: Based on the relationship between the death of COPD and exposure to risk factors and the theory of comparative risk assessment, we used the estimates of the Global Burden of Disease Study 2015 (GBD2015) for China, targets for controlling risk factors, and proportion change model to project the number of deaths, standardized mortality rate, and probability of premature mortality from chronic respiratory diseases by 2030 in different scenarios and to evaluate the impact of controlling the included risk factors to the disease burden of COPD in 2030. Results: If the trends in exposure to risk factors from 1990 to 2015 continued, the number of deaths and the mortality for COPD would be 1.06 million and 73.85 per 100 000 population in China by 2030, respectively, with an increase of 15.81% and 10.69% compared to those in 2015. Compared to 2015, the age-standardized mortality rate would decrease by 38.88%, and the premature mortality would reduce by 52.73% by 2030. If the smoking rate and fine particulate matter (PM2.5) concentration separately achieve their control targets by 2030, there would be 0.34 and 0.27 million deaths that could be avoided compared to the predicted numbers based on the natural trends in exposure to risk factors and the probability of premature death would reduce to 0.59% and 0.52%, respectively. If the control targets of all included risk factors were achieved by 2030, a total of 0.53 million deaths would be averted, and the probability of premature death would decrease to 0.44%. Conclusions: If the exposures to risk factors continued as showed from 1990 to 2015, the number of deaths and mortality for COPD would increase by 2030 compared to 2015, and the standardized mortality and the probability of premature death would decrease significantly, which would achieve the targets of preventing and controlling COPD. If the exposure to the included risk factors all achieved the targets by 2030, the burden of COPD would be reduced, suggesting that the control of tobacco use and air pollution should be enhanced to prevent and control COPD.

[Prediction of disease burden caused by malignant cancer in the context of risk factor control in China, 2030].

Objective: To predict the number of deaths, standardized mortality and probability of premature mortality caused by malignant cancer in the context of risk factor control at different levels in China in 2030, and assess the possibility of achieving the target of reducing the probability of premature mortality of malignant cancer. Methods: According to the risk factor control standard for malignant cancer used both at home and abroad, the results of China from Global Burden of Disease Study 2015 were used to calculate the population attributable fraction of the risk factors. Based on the comparative risk assessment theory, the deaths of malignant cancer were classified as attributable deaths and un-attributable deaths. Proportional change model was used to predict risk factor exposure and un-attributable deaths of malignant cancer in the future, then the number of deaths, standardized mortality rate and probability of premature mortality of malignant cancer in 2030 was estimated. Data analyses were performed by using software R 3.6.1. Results: If the risk factor exposure level during 1990-2015 remains, the number of deaths, standardized mortality rate, and probability of premature mortality of malignant cancer would increase to 3.62 million, 153.96/100 000 and 8.92% by 2030, respectively. If the risk factor exposure control level meets the requirement, the probability of premature mortality from cancer in people aged 30-70 years would drop to 7.57% by 2030. Conclusions: The control of risk factor exposure will play an important role in reducing deaths, standardized mortality rate and probability of premature mortality of malignant cancer. But more efforts are needed to achieve the goals of Health China Action.

Engineered Saccharomyces cerevisiae that produces 1,3-propanediol from D-glucose.

AIMS: Saccharomyces cerevisiae is a safe micro-organism used in fermentation industry. 1,3-Propanediol is an important chemical widely used in polymer production, but its availability is being restricted owing to its expensively chemical synthesis. The aim of this study is to engineer a S. cerevisiae strain that can produce 1,3-propanediol at low cost. METHODS AND RESULTS: By using D-glucose as a feedstock, S. cerevisiae could produce glycerol, but not 1,3-propanediol. In this study, we have cloned two genes yqhD and dhaB required for the production of 1,3-propanediol from glycerol, and integrated them into the chromosome of S. cerevisiae W303-1A by Agrobacterium tumefaciens-mediated transformation. Both genes yqhD and dhaB functioned in the engineered S. cerevisiae and led to the production of 1,3-propanediol from D-glucose. CONCLUSION: Saccharomyces cerevisiae can be engineered to produce 1,3-propanediol from low-cost feedstock D-glucose. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report on developing S. cerevisiae to produce 1,3-propanediol by using A. tumefaciens-mediated transformation. This study might lead to a safe and cost-efficient method for industrial production of 1,3-propanediol.

Toxicity and growth inhibition potential of vetiver, cinnamon, and lavender essential oils and their blends against larvae of the sheep blowfly, Lucilia sericata.

BACKGROUND: Myiasis induced by the sheep blowfly, Lucilia sericata, represents a public health problem widely distributed throughout the world. L. sericata larval stages feed on both humans and animals. L. sericata adults and larvae can play a role in spreading agents of mycobacterial infections. OBJECTIVES: It is critical to establish new and safe alternative methods of controlling L. sericata. METHODS: The insecticidal effectiveness and growth inhibition potential of three commercially available essential oils (EOs), vetiver (Chrysopogon zizanioides), cinnamon (Cinnamomum zeylanicum), and lavender (Lavandula angustifolia), as well as their blends, were tested against the second (L2) and third (L3) larval stages of L. sericata. Sunflower (Helianthus annuus) oil was used as a carrier and tested on L2 and L3 larvae. To the best of our knowledge, all applied essential oils, except lavender, and oil blends were tested against L. sericata for the first time. RESULTS: All applied oils did not repel L2 from the treated liver but adversely affected their development. Contact treatments on L. sericata L3 indicated that vetiver and cinnamon oils significantly affected treated larvae. Total mortality rates were 93.33 and 95.56%, respectively. Furthermore, oil blends tested through contact assays killed larvae when used at higher concentrations; adult emergence was eliminated post-treatment with doses >30% for oil blend 1 and >10% for oil blend 2. CONCLUSION: Overall, cinnamon and vetiver oils (5%) were selected as reliable and cheap biopesticides for controlling larvae of L. sericata. The tested oils are inexpensive and represent new promising botanical insecticides in the fight against blowflies causing myiasis.

Human 8-oxoguanine DNA glycosylase increases resistance to hyperoxic cytotoxicity in lung epithelial cells and involvement with altered MAPK activity.

It is unknown whether base excision DNA repair (BER) proteins interact with mitogen-activated protein kinases (MAPK) under oxidation. Here, we explored roles of BER proteins in signaling transduction involving MAPK during hyperoxia. We demonstrated that ERK1/2 phosphorylation in A549 cells was increased in 95% O(2). p38 activity in A549 cells was also increased by exposure to 95% O(2). To evaluate regulatory roles of MAPK, we have transduced A549 cells and primary alveolar epithelial type II cells (AECII) to overexpress 8-oxoguanine DNA glycosylase (hOgg1). Overexpression of hOgg1 reduced hyperoxic toxicity in A549 and AECII cells. Furthermore, protection by BER against hyperoxia appeared to involve an upregulation of ERK1/2 and downregulation of p38. These observations demonstrate, for the first time, that reduction of hyperoxic toxicity by BER proteins may be involved with MAPK activity, thereby impacting cell survival. Furthermore, our studies suggest that modulation of MAPK may be used in combination with BER proteins to counteract hyperoxic toxicity.

Comparison of Both Sides for Retroperitoneal Laparoscopic Donor Nephrectomy: Experience From a Single Center in China.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) has gradually become the main approach to obtain live donor kidneys. However, the shorter right renal vein limits its wider application. The aim of this study was to compare the outcomes of left- and right-side retroperitoneal LDN. METHODS: We reviewed the perioperative data of 527 consecutive donors receiving retroperitoneal pure LDN with a new method at our center between April 2009 and April 2014. The patients were divided into group A (the first 100 patients) and group B (the remaining 427 patients). A total of 423 cases of left donor surgery and 104 cases of right donor surgery were compared. The comparison of the laterality of LDN was also performed between group A and group B. RESULTS: This is currently the largest case series of LDN in our country. Although right-side LDN patients had longer operation time and a slightly higher incidence of intraoperative complications compared with left-side LDN patients, the operation time was shorter in both the groups compared with previous reports. In group B, patients undergoing right-side LDN had longer operation time and more frequent complications. Once the learning curve of 100 cases was completed, the incidence of complications and operation time were greatly reduced in both sides for LDN. There was no significant difference in the serum creatinine levels in recipients at 6 months of follow-up. CONCLUSIONS: Despite a slightly higher incidence of complications and longer operation time, right-side LDN can achieve equally safe and effective transplantation outcomes. This expands the source of potential donor kidneys.

Conversion From Calcineurin Inhibitors to Mammalian Target-of-Rapamycin Inhibitors in Heart Transplant Recipients: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Conversion from calcineurin inhibitors (CNIs) to mammalian target-of-rapamycin inhibitors (mTORi) was systematically evaluated in heart transplant recipients (HTRs) for the first time. METHODS: MEDLINE (PUBMED), EMBASE, Cochrane Library, and clinical trial registries were searched comprehensively. After screening for eligibility, the randomized controlled trials (RCTs) comparing continuation of CNI with conversion to mTORi therapy underwent review, quality assessment, and data extraction. Outcomes analyzed including creatinine clearance, serum creatinine level, rejection, adverse effects, and triglyceride levels were expressed as mean differences (MDs) or as risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: This is the first systematic review evaluating converting from CNI to mTORi therapy in HTRs. A total of 4 RCTs (231 HTRs, 117 vs 114) were included in our analysis. Patients converted to mTORi had a higher creatinine clearance (MD, 19.31; 95% CI [11.16, 27.46]; P < .00001) and lower serum creatinine levels (MD, -0.15; 95% CI [-0.25, -0.05]; P = .002). Patients converted to mTORi had a significantly higher occurrence of adverse effects, which included skin diseases, gastrointestinal side effects, bone marrow suppression, and infections. There was no significant difference between the 2 groups regarding graft rejection and triglyceride levels (RR, 2.61; 95% CI [0.08, 81.25]; P = .58; MD, 22.89; 95% CI [-21.86, 67.63]; P = .32). CONCLUSIONS: Conversion from CNI to mTORi therapy may improve the renal function in HTRs, but the patients may suffer from a high incidence of mTORi-associated adverse events. Therefore, conversion to mTORi must be carefully assessed for the benefits and risks.

Evidence of gamma-aminobutyric acidergic control over the catecholaminergic projection from the medulla oblongata to the central nucleus of the amygdala.

It is known that the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) project to the central nucleus of the amygdala (Ce), conveying visceral information. Conversely, the Ce sends projections to the NTS and the VLM. To understand better the role of catecholamine and gamma-aminobutyric acid (GABA) in these reciprocal connections, experiments were performed by combining lectin-conjugated horseradish peroxidase (WGA-HRP) anterograde and retrograde transport with preembedding immunocytochemistry to detect tyrosine hydroxylase (TH), and postembedding immunocytochemistry to detect GABA. The light microscopic study suggested that the majority of neurons in the NTS and the VLM projecting to the Ce were TH immunoreactive (TH-IR). Most of them were located at the level of the obex. Under the electron microscope, the GABAergic and non-GABAergic terminals were found to form synaptic contacts with the TH-(IR) or Ce-projecting or TH-IR/Ce-projecting double-labelled neurons of the NTS and VLM. The GABAergic terminals mostly formed symmetrical synaptic contacts with the postsynaptic structure in which perikarya (14-19%), dendrites (79-84%), and spines (2%) were observed. Approximately 94% of the axon terminals in the NTS and 90% of those in the VLM arising from the Ce were GABAergic and appeared not to form synaptic contacts with the TH-IR or Ce-projecting neurons in these regions. The present results demonstrated that the catecholaminergic neurons of the NTS and VLM projecting to the Ce receive an extensive GABAergic innervation and that the amygdala projection to the medulla is mostly GABAergic.

Distribution of cholinergic neurons and fibers in the hypothalamus of the rat using choline acetyltransferase as a marker.

The distribution of choline-acetyltransferase-like immunoreactive structures in the rat hypothalamus and preoptic area was examined by using avidin-biotin immunocytochemistry. We found that the hypothalamus is richly innervated by the cholinergic neuron system. Sites containing cholinergic neurons of varying density were: medial and lateral preoptic areas, septohypothalamic nucleus, median preoptic area, lateral hypothalamus including the perifornical area, anterior hypothalamic nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, posterior hypothalamic nucleus, dorsal and ventral premammillary nuclei, neuropil mediodorsal to the anterior hypothalamic nucleus, neuropil ventral to the anterior hypothalamic nucleus and ventromedial hypothalamic nucleus, neuropil between lateral hypothalamus and ventromedial hypothalamus, and neuropil between dorsal premammillary nucleus and posterior hypothalamic nucleus. There were also many varicose and non-varicose fibers in the preoptic area and hypothalamus. Two kinds of varicose fibers, one with strong immunoreactivity and the other with weak immunoreactivity, were seen. Non-varicose fibers were also detected in the optic chiasma and habenulo-interpeduncular tract. These fibers were passing fibers.