Exploring the influence of sulfadiazine-induced stress on antibiotic removal and transformation pathway using microalgae Chlorella sp.

Sulfadiazine (SDZ) is a kind of anti-degradable antibiotics that is commonly found in wastewater, but its removal mechanism and transformation pathway remain unclear in microalgal systems. This study investigated the effects of initial algae concentration and SDZ-induced stress on microalgal growth metabolism, SDZ removal efficiency, and transformation pathways during Chlorella sp. cultivation. Results showed that SDZ had an inhibitory effect on the growth of microalgae, and increasing the initial algal biomass could alleviate the inhibitory effect of SDZ. When the initial algal biomass of Chlorella sp. was increased to 0.25 g L-1, the SDZ removal rate could reach 53.27%-89.07%. The higher the initial algal biomass, the higher the SOD activity of microalgae, and the better the protective effect on microalgae, which was one of the reasons for the increase in SDZ removal efficiency. Meanwhile, SDZ stress causes changes in photosynthetic pigments, lipids, total sugars and protein content of Chlorella sp. in response to environmental changes. The main degradation mechanisms of SDZ by Chlorella sp. were biodegradation (37.82%) and photodegradation (23%). Most of the degradation products of SDZ were less toxic than the parent compound, and the green algae were highly susceptible to SDZ and its degradation products. The findings from this study offered valuable insights into the tradeoffs between accumulating microalgal biomass and antibiotic toxic risks during wastewater treatment, providing essential direction for the advancement in future research and full-scale application.

Effects of Hydrothermal Pretreatment and Anaerobic Digestion of Pig Manure on the Antibiotic Removal and Methane Production.

Whether advanced biological waste treatment technologies, such as hydrothermal pretreatment (HTP) integrated anaerobic digestion (AD), could enhance the removal of different antibiotics remains unclear. This study investigated the outcome of antibiotics and methane productivity during pig manure treatment via HTP, AD, and HTP + AD. Results showed improved removal efficiency of sulfadiazine (SDZ), oxytetracycline (OTC), and enrofloxacin (ENR) with increased HTP temperatures (70, 90, 120, 150, and 170 °C). OTC achieved the highest removal efficiency of 86.8% at 170 °C because of its high sensitivity to heat treatment. For AD, SDZ exhibited resistance with a removal efficiency of 52.8%. However, OTC and ENR could be removed completely within 30 days. When HTP was used prior to AD, OTC and ENR could achieve complete removal. However, residual SDZ levels reduced to 20% and 16% at 150 and 170 °C, respectively. The methanogenic potential showed an overall upward trend as the HTP temperature increased. Microbial analysis revealed the antibiotics-induced enrichment of specific microorganisms during AD. Firmicutes were the dominant bacterial phylum, with their abundance positively correlated with the addition of antibiotics. Methanobacterium and Methanosarcina emerged as the dominant archaea that drove methane production during AD. Thus, HTP can be a potential pretreatment before AD to reduce antibiotic-related risks in manure waste handling.

The predictive utility of cytokines, procalcitonin and C-reactive protein among febrile pediatric hematology and oncology patients with severe sepsis or septic shock.

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

Prognostic performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal procalcitonin.

INTRODUCTION: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT. METHODS: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia. RESULTS: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia. CONCLUSIONS: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.

Effect of reactor operation modes on mitigating antibiotic resistance genes (ARGs) and methane production from hydrothermally-pretreated pig manure.

Numerous efforts have been made to enhance the performance of anaerobic digestion (AD) for accelerating renewable energy generation, however, it remains unclear whether the intensified measures could enhance the proliferation and transmissions of antibiotic resistance genes (ARGs) in the system. This study assessed the impact of an innovative pig manure AD process, which includes hydrothermal pretreatment (HTP) and a two-stage configuration with separated acidogenic and methanogenic phases, on biomethane (CH4) production and ARGs dynamics. Results showed that HTP significantly increase CH4 production from 0.65 to 0.75 L/L/d in conventional single-stage AD to 0.82 and 0.91 L/L/d in two-stage AD. This improvement correlated with a rise in the relative abundance of Methanosarcina, a key methanogenesis microorganism. In the two-stage AD, the methanogenic stage offered an ideal environment for methanogens growth, resulting in substantially faster and higher CH4 production by about 10% compared to single-stage AD. Overall, the combined use of HTP and the two-stage AD configuration enhanced CH4 production by 40% compared to traditional single-stage AD. The abundance and diversity of ARGs were significantly reduced in the acidogenic reactors after HTP. However, the ARGs levels increased by about two times in the following methanogenesis stage and reached similar or higher levels than in single stage AD. The erm(F), erm(G), ant(6)-Ia, tet(W), mef(A) and erm(B) were the six main ARGs with significant differences in relative abundances in various treatments. The two-stage AD mode could better remove sul2, but it also had a rebound which elevated the risk of ARGs to the environment and human health. Network analysis identified pH and TVFAs as critical factors driving microbial communities and ARG proliferation in the new AD process. With the results, this study offers valuable insights into the trade-offs between AD performance enhancement and ARG-related risks, pinpointing essential areas for future research and practical improvements.

A Prediction Model for Acute Kidney Injury in Adult Patients With Minimal Change Disease.

Background: Early prediction of acute kidney injury (AKI) can allow for timely interventions, but there are still few methods that are easy and convenient to apply in predicting AKI, specially targeted at patients with minimal change disease (MCD). Motivated by this, we aimed to develop a predicting model for AKI in patients with MCD within the KDIGO criteria. Methods: Data on 401 hospitalized adult patients, whose biopsy was diagnosed as MCD from 12/31/2010 to 15/7/2021, were retrospectively collected. Among these data, patients underwent biopsy earlier formed the training set (n = 283), while the remaining patients formed the validation set (n = 118). Independent risk factors associated with AKI were analyzed. From this, the prediction model was developed and nomogram was plotted. Results: AKI was found in 55 of 283 patients (19%) and 15 of 118 patients (13%) in the training and validation cohorts, respectively. According to the results from lasso regression and logistic regression, it was found that four factors, including mean arterial pressure, serum albumin, uric acid, and lymphocyte counts, were independent of the onset of AKI. Incorporating these factors, the nomogram achieved a reasonably good concordance index of 0.84 (95%CI 0.77-0.90) and 0.75 (95%CI 0.62-0.87) in predicting AKI in the training and validation cohorts, respectively. Decision curve analysis suggested clinical benefit of the prediction models. Conclusions: Our predictive nomogram provides a feasible approach to identify high risk MCD patients who might develop AKI, which might facilitate the timely treatment.

Efficacy of umbilical cord mesenchymal stem cell transfusion for the treatment of severe AKI: a protocol for a randomised controlled trial.

INTRODUCTION: Acute kidney injury (AKI) is a common and severe clinical problem that is associated with high mortality, a long hospital stays and high healthcare resource consumption. Approximately a quarter of AKI survivors will develop chronic kidney disease. Mesenchymal stem cells (MSCs) are multipotent stem cells with antiapoptotic, immunomodulatory, antioxidative and proangiogenic properties. Therefore, MSCs have been considered as a potential new therapy for the treatment of AKI. Several clinical trials have been performed, but the results have been inconsistent. This trial investigated whether MSCs can improve renal recovery and mortality in patients with severe AKI. METHODS AND ANALYSIS: One hundred subjects suffering from severe AKI will participate in this patient-blinded, randomised, placebo-controlled, parallel design clinical trial. Participants will be randomly assigned to receive two doses of MSCs or placebo (saline) on days 0 and 7. Urinary biomarkers of renal injury and repair will be measured using commercially available ELISA kits. The main outcome measures are changes in renal function levels within the first 28 days following MSC infusion. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the Chinese PLA General Hospital. The findings of the study will be disseminated through public and scientific channels. TRIAL REGISTRATION NUMBER: NCT04194671.

Mitochondrial genomes of five Hyphessobrycon tetras and their phylogenetic implications.

To date, the taxonomic status and phylogenetic affinities within Hyphessobrycon, even among other genera in Characidae, remain unclear. Here, we determined five new mitochondrial genomes (mitogenomes) of Hyphessobrycon species (H. elachys, H. flammeus, H. pulchripinnis, H. roseus, and H. sweglesi). The mitogenomes were all classical circular structures, with lengths ranging from 16,008 to 17,224 bp. The type of constitutive genes and direction of the coding strand that appeared in the mitogenomes were identical to those of other species in Characidae. The highest value of the Ka/Ks ratio within 13 protein-coding genes (PCGs) was found in ND2 with 0.83, suggesting that they were subject to purifying selection in the Hyphessobrycon genus. Comparison of the control region sequences among seven Hyphessobrycon fish revealed that repeat units differ in length and copy number across different species, which led to sharp differences in mitogenome sizes. Phylogenetic trees based on the 13 PCGs did not support taxonomic relationships, as the Hyphessobrycon fish mixed with those from other genera. These data were combined to explore higher level relationships within Characidae and could aid in the understanding of the evolution of this group.

Comparative mitogenomes of three species in Moenkhausia: Rare irregular gene rearrangement within Characidae.

Generally, a teleostean group possesses only one type or a set of similar mitochondrial gene arrangements. However, a new type of gene arrangement has been identified in the mitochondrial genomes (mitogenomes) of Moenkhausia. Here, three newly sequenced complete mitogenomes of tetras (Characidae: Moenkhausia) are presented (M. costae, M. pittieri, and M. sanctaefilomenae). The three mitogenomes had a classical circular structure, with total lengths ranging from 15,811 to 18,435 bp. Base composition analysis indicated that the sequences were biased toward adenine (A) and thymine (T), with A + T content of 54.63% in M. costae, 58.47% in M. pittieri, and 59.98% in M. sanctaefilomenae. The gene order and organization of M. sanctaefilomenae differed from those of typical teleostean mitogenomes. The genes tRNA-Ile, tRNA-Gln, and tRNA-Pro were translocated between tRNA-Trp and tRNA-Asn. One extra tRNA-Met and an extra CR were also discovered in the mitogenome. BI and ML analyses based on sequences of 38 different mitogenomes showed that M. costae and M. pittieri were classified together, and M. sanctaefilomenae was slightly further from other fish of the same genus. These results provide insight into the gene arrangement features of Characidae mitogenomes and lay the foundation for further phylogenetic studies on Characidae.

Evaluating the safety and efficacy of argatroban locking solution in the prevention of the dysfunction of haemodialysis central venous catheters: a study protocol for a randomized controlled trial.

BACKGROUND: Use of anticoagulant as lock solutions is an important method to maintain the function of haemodialysis (HD) central venous catheters (CVCs), and the common anticoagulants heparin and citrate are not suitable for some patients. Argatroban can inhibit thrombin directly, has a definite anticoagulant effect, and is expected to be a new anticoagulant for CVC lock solutions. METHODS: A total of 60 HD patients with non-tunnelled or tunnelled CVCs will be randomly assigned to two groups: an argatroban group and a control group. The participants will be given argatroban 0.5 mg/mL or unfractionated heparin (UFH) 1,000 U/mL locked post-dialysis instilled into the CVC lumens and followed up for 2 weeks. Data on demographic and general clinical information, laboratory examination, adverse events, adverse reactions and serious adverse events in the two groups will be collected. The differences in coagulation indexes at 30 min following catheter lock will be compared. The thrombosis rate, infection rate and percentage of catheter-days in the two groups will be observed. The primary outcomes include: efficacy assessments of combined outcome events: (I) rates of cumulative catheter survival in the 2-week HD session (the standard of catheter survival was catheter mean blood flow ≥250 mL/min); (II) rates of cumulative survival free of catheter thrombosis in the 2-week HD session. The second outcomes include: catheter dysfunction, the variation value (seconds) in activated partial thromboplastin time (aPTT) at 30 min following catheter locking and aPTT before next dialysis, catheter-associated bleeding, and catheterassociated infections. DISCUSSION: At present, there is no clinical study of argatroban as a CVC lock solution. This study will explore the efficacy and safety of the argatroban as locking solution in the prevention of the dysfunction of HD CVCs to provide evidence for further research. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017105. Registered 12 July, 2018 (prospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=29054).

GLA missense and promoter variants co-segregating in a Chinese family with Fabry disease.

BACKGROUND: Fabry disease (FD) is an X-linked recessive inheritance lysosomal storage disorder due to mutations in the GLA gene leading to deficiency of lysosomal α-galactosidase A (α-Gal A) and has a wide range of clinical presentations. Over 900 GLA gene mutations are currently known and of those most are thought not to be clinically significant, some with doubtful clinical significance, posing diagnostic and prognostic difficulties for the clinician. METHODS: Whole-exome sequencing (WES) was performed to detect the mutation in family members with Fabry disease. The function of g.1170C>T mutation was confirmed by dual luciferase system. RESULTS: A total of 1,375 variants were found in a Chinese family with FD. A missense variants c.1025C>T (p.Arg342Gln) which have been previously reported in association with FD and g.1170C>T single-nucleotide polymorphism (SNP) in the GLA gene were found in five patients. The g.1170C>T SNP affects transcription of GLA gene, presumably the transcription start site. Female patients only have hypohidrosis and neuropathic pain, while male patients have severe symptoms with simultaneous renal impairment. CONCLUSIONS: Two simultaneous variants in cis of the GLA gene, c.1025C>T (p.Arg342Gln) and g.1170C>T, were verified in Chinese individuals, and the corresponding clinical symptoms were described. The disease severity in male patients is worse than in female patients. These results may be helpful for genetic counseling, diagnosis and prognosis of patients with FD.

Clinical features of acute kidney injury in patients with nephrotic syndrome and minimal change disease: a retrospective, cross-sectional study.

BACKGROUND: Minimal change nephropathy (MCD) is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury (AKI). This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome. METHODS: Patients from Chinese People's Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1, 2013 to December 31, 2017. Patients diagnosed with membranous nephropathy (MN) by renal biopsy from January 1, 2013 to December 31, 2017 are included as a control population. We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups. We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis. RESULTS: A total of 367 patients with MCD were included in the analysis, with a sex ratio of 1.46: 1 (male: female) and an age range of 6 to 77 years. Among all the patients, 109 developed AKI (29.7%), and of these patients, 85 were male (78.0%). In the 586 patients with MN, 27 (4.6%) patients developed AKI. The percentage of AKI in MCD patients was significantly higher than that in MN patients (χ2 = 41.063, P < 0.001). The percentage of AKI increased with age in the MCD patients. The percentage of AKI in patients aged 50 years or older was 52.9% (46/87), which was significantly higher than that [22.5% (63/280)] in patients under 50 years (χ2 = 6.347, P = 0.013). We observed statistically significant differences in age (43 [27, 59] years vs. 28 [20, 44] years, Z = 5.487, P < 0.001), male (78.0% vs. 51.4%, χ2 = 22.470, P < 0.001), serum albumin (19.9 ±â€Š6.1 g/L vs. 21.5 ±â€Š5.7 g/L, t = 2.376, P = 0.018), serum creatinine (129.5 [105.7, 171.1] µmol/L vs. 69.7 [57.7, 81.9] µmol/L, Z = 14.190, P < 0.001), serum urea (10.1 [6.2, 15.8] mmol/L vs. 4.7 [3.6, 6.4] mmol/L, Z = 10.545, P < 0.001), IgE (266.0 [86.7, 963.0] IU/ml vs. 142.0 [35.3, 516.5] IU/ml, Z = 2.742, P = 0.007), history of diabetes (6.4% vs. 1.2%, P = 0.009), and history of hypertension (23.9% vs. 5.1%, χ2 = 28.238, P < 0.001) between the AKI group and the non-AKI group. According to multivariate linear regression analysis, among the renal pathological features analyzed, renal tubular epithelial cell damage (ß = 178.010, 95% CI: 147.888-208.132, P < 0.001) and renal interstitial edema (ß = 28.833, 95% CI: 11.966-45.700, P = 0.001) correlated with serum creatinine values. CONCLUSIONS: The percentage of AKI in MCD patients is significantly higher than that in MN patients. Patients over 50 years old are more likely to develop AKI. Renal tubular epithelial cell injury and renal interstitial edema may be the main pathological lesions that are associated with elevated serum creatinine in patients with MCD.

Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy.

BACKGROUND/AIMS: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. METHODS: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). RESULTS: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21-0.74; Oxford classification 0.48, 95% CI 0.28-0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23-0.92; Oxford classification 0.59, 95% CI 0.10-0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. CONCLUSIONS: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.

N-Acetylcysteine Ameliorates Gentamicin-Induced Nephrotoxicity by Enhancing Autophagy and Reducing Oxidative Damage in Miniature Pigs.

The clinical use of gentamicin over prolonged periods is limited because of dose and time-dependent nephrotoxicity, in which intracellular oxidative stress and heightened inflammation have been implicated. Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. The aim of this study was to determine changes in autophagy in response to the antioxidant N-acetylcysteine (NAC), via its effects on oxidative stress, inflammation, apoptosis, and renal function, following treatment with gentamicin in mini pigs. Adult mini pigs were divided into isotonic saline solution, gentamicin, and gentamicin plus NAC combination treatment groups. Gentamicin-induced histopathological changes, including inflammatory cell infiltration and tubular necrosis, were attenuated by NAC. NAC ameliorated the gentamicin-induced decreases in the levels of autophagy-related proteins, such as LC3 (microtubule-associated protein 1 light chain 3), PINK1 (phosphatase and tensin homologue deleted on chromosome10-induced kinase 1), phospho-parkin, AMBRA1 (activatingmolecule in Beclin 1-regulated autophagy), p62/SQSTM1 (sequestosome protein 1), and polyubiquitinated protein aggregates. NAC also caused a significant reduction in oxidative damage markers, including 4-hydroxy-2-nonenal, protein carbonyls, γ-H2AX (gamma histone variant H2AX), and 8-hydroxy-2'-deoxyguanosine, in gentamicin-treated animals. These data show that the protective effects of NAC might be related, at least in part, to a reduced inflammatory response, as observed in animals treated with both gentamicin and NAC. These results suggest that autophagy could be a new therapeutic target for preventing gentamicin-induced kidney injury, and that NAC might ameliorate gentamicin-induced nephrotoxicity by autophagy.

The combination of metformin and 2-deoxyglucose significantly inhibits cyst formation in miniature pigs with polycystic kidney disease.

BACKGROUND AND PURPOSE: The pathogenic mechanism of autosomal dominant polycystic kidney disease (ADPKD) is unclear. Similar to tumour cells, polycystic kidney cells are primarily dependent on aerobic glycolysis for ATP production. Compared with rodents, miniature pigs are more similar to humans. This study is the first time to investigate the effects of the combination of metformin and 2-deoxyglucose (2DG) in a pig model of chronic progressive ADPKD. EXPERIMENTAL APPROACH: A miniature pig ADPKD model was established by inducible deletion of the PKD1 gene. Blood, urine and kidney biopsy specimens were collected for analysis at specific times. The renal vesicle index was analysed by three-dimensional reconstruction of CT scans. Markers of the mammalian target of rapamycin (mTOR) and ERK signalling pathways and associated metabolism were detected by Western blots and colorimetry. KEY RESULTS: The three-dimensional reconstruction of CT scans indicated a markedly lower renal vesicle index in the combination therapy group. Each drug intervention group showed a significantly lower serum creatinine and urinary protein/creatinine ratio. This treatment regimen also inhibited the activities of markers of the proliferation-related mTOR and ERK pathways, and the expression of key enzymes involved in glycolysis, as well as reducing the production of ATP and lactic acid. CONCLUSIONS AND IMPLICATIONS: This study showed that the combination of metformin and 2DG blocked the formation of renal cysts and improved the renal function in ADPKD miniature pigs. Our results indicate that the combination of metformin and 2DG may be a promising therapeutic strategy in human ADPKD.

Preliminary experience with tigecycline treatment for severe infection in children.

Severe infection is a primary cause of mortality in children facing challenges from multidrug-resistant (MDR) pathogens, particularly MDR Acinetobacter baumannii. Tigecycline has an expanded spectrum of antibacterial activity, and some successful instances of its use in children have been reported. We conducted a retrospective chart review of children treated at a tertiary hospital between May 1, 2012 and May 1, 2017 to examine the efficacy and safety of tigecycline in children with severe infection. A total of 110 patients (69 males) were enrolled in this study, including 46 MDR A. baumannii infection patients, encompassing 51 A. baumannii strains. Totally, the median duration of tigecycline therapy was 10 days (range, 2-47 days), with a clinical improvement rate of 47.27% (52/110). In A. baumannii infection group, the clinical improvement rate was 50% (23/46) and the microbiology eradication rate was 50.98% (26/51). No adverse events were reported during therapy; however, in one case, a 9-year-old boy with hematologic disease developed tooth discoloration.Conclusion: Although some patients benefited from tigecycline, the efficacy and safety of tigecycline should not be overvalued. Additional data from randomized controlled trials are required to assess the administration of tigecycline. What is Known: • Severe infection is a primary cause of mortality in pediatric patients and its treatment is facing challenges from an increasing number of multidrug-resistant (MDR) pathogens. • Tigecycline has an expanded spectrum of antibacterial activity. • Several case reports have indicated that tigecycline could be used as a salvage therapy in children when options are limited or non-existent. What is New: • We found that rate of clinical improvement was different in various groups of different infection. The efficacy of tigecycline should not be overvalued. • Six dosage models and different infection types were observed in our series, with different improvement and eradication rate, indicating that more data are required to identify a proper tigecycline dosage.

Preliminary experience of tigecycline treatment for infection in children with hematologic malignancies.

Background Severe infection is life-threatening in children with hematologic malignancies and its treatment is challenging because of an increasing number of multidrug-resistant pathogens. Tigecycline has an expanded antibacterial activity spectrum; some successful cases of tigecycline treatment have been reported in the literature. Objective To examine the efficacy and safety of tigecycline in children. Setting Department of hematologic malignancies in a tertiary hospital. Method A retrospective chart review from May 1, 2012 to May 1, 2017. The patients were identified by the hospital information system and a custom-made Microsoft Excel 2007 database of patients was created to record demographic and medical data. Main outcome measure Efficacy and safety of tigecycline use in severe infection children with hematologic malignancies. Results Thirty-seven patients were enrolled and the predominant diagnosis was acute lymphoblastic leukemia. The median duration of tigecycline therapy was 9 days. Most prescriptions were empirical. Eighteen patients received a maintenance dose of 2 mg/kg q12 h, without a loading dose. Sulperazone was the most frequently prescribed concomitant drug. At the end of tigecycline therapy, improvement was observed in 48.7% of cases. After treatment, interleukin-10 levels notably decreased. The only reported adverse event was a case of tooth discoloration. Conclusion Tigecycline can be used as salvage therapy in children with hematologic malignancy and seems tolerable. Prospective controlled studies are required to definitively evaluate the efficacy and safety of tigecycline in children.

Effect of Huaier On the Proliferation of Mesangial Cells in Anti-Thy-1 Nephritis.

BACKGROUND/AIMS: To determine whether an aqueous extract of Trametes robiniophila Murr. (Huaier) suppresses anti-Thy-1 mesangial proliferative glomerulonephritis (MsPGN) in vivo and platelet-derived growth factor (PDGF)-BB-induced mesangial cell proliferation in vitro. METHODS: Male Wistar rats were randomly categorized into 5 groups: Sham, Thy-1, and 3 Huaier-treated groups (low, medium, and high dose). Two weeks after treatment, urinary proteins were quantified and renal pathological changes were examined. MAX interactor 1 (Mxi-1) and proliferating cell nuclear antigen (PCNA) expression levels in isolated glomeruli, rat mesangial cell viability, cell-cycle distribution, and cell-cycle pathways were assessed. RESULTS: Huaier diminished the proliferative damages and urinary protein secretion in Thy-1 rats. PCNA was downregulated, whereas Mxi-1 was upregulated in the isolated glomeruli of Huaier-treated groups compared with the Thy-1 group. Huaier inhibited PDGF-BB- stimulated proliferation of rat mesangial cells in a time- and dose-dependent manner (50% inhibitory concentration = 6.19 mg/mL) and induced G2 cell-cycle arrest. Cell-cycle pathway proteins were downregulated, whereas Mxi-1 was upregulated in Huaier-treated mesangial cells compared with PDGF-BB-stimulated cells. CONCLUSION: Huaier reduces urinary protein excretion and relieves hyperplasia in mesangial cells in anti-Thy-1 MsPGN as well as inhibits PDGF-BB-stimulated proliferation and DNA synthesis of rat mesangial cells in vitro, suggesting its novel therapeutic potential in MsPGN.